Liquid Suspension Research Articles

Optical Signatures of Phosphorene Chemical Evolvement in Liquid Environment

Phosphorene possesses a unique combination of physical and chemical properties, including tunable direct bandgap, anisotropic electronic and optical properties. However, application of phosphorene is hampered by its fast degradation under ambient conditions. It is believed that H2O and O2 play key roles in the instability of phosphorene, but their exact contributions have not yet been completely understood in experiment. Herein, a technique of probing the mechanism of phosphorene oxidation through the evolvement of its photoluminescence spectra in a liquid suspension is introduced. With the addition of H2O2, the photoluminescence intensity of the suspension surprisingly increases, indicating a passivation effect due to the formation of phosphorene oxide, which is also verified by Raman spectroscopy. In contrast, direct addition of H2O leads to irreversible and rapid degradation as shown by the quenching of photoluminescence. Furthermore, monolayer phosphorene suspension photoluminescence at 2.17 eV is obtained by completely eliminating effects from contaminations, substrate strain, dielectric substrate, and oxidation of samples. Solvent protection in combination with the optical probing method provides an effective approach in investigating the chemistry of active materials like phosphorene. Phosphorene has great potential in the range of sensing applications including high‐resolution H2O2 and humidity sensors.

A SERS Responsive DGT Sensing Device for On-Site Determination of Organic Contaminants Underwater.

Although diffusion gradient in the thin-film technique (DGT) is highly regarded in environmental analysis, the traditional DGT devices cannot serve as sensing devices but in situ sampling devices. Here we report a surface enhanced Raman scattering (SERS) responsive DGT sensing device (SERS-DGT Sensor) capable of on-site determination of organic contaminants underwater. This is achieved by innovatively utilizing a SERS responsive liquid suspension of Au nanoparticles supported on graphene oxide (AuNPs@GO) as the DGT binding phase. Liquid suspension is synthesized via a combined secondary growth and molecular welding approach and used as DGT binding phase AuNPs@GO exhibit good SERS activity, aqueous stability, and adsorption performance. Based on the development time range of 24-144 h, the measurement of sulfadiazine (SMT) by SERS-DGT Sensor is evaluated in the concentration range of 0.3289-2631 ng mL-1. The SERS-DGT sampler is valid for measuring SMT under a wide range of environmental conditions (i.e, pH 5-9, ionic strength 0.0001-0.05 mol L-1 NaCl, DOM concentrations 0-100 mg L-1, the values of TC: SMT ≤ 20 and MNZ: SMT ≤ 20). SERS-DGT Sensor is applied to the practical test of SMT content in pig breeding wastewater, and compared with the grab sampling method, the results confirm that this novel hyphenated technique exhibits good accuracy and precision. The platform proves to be versatile by extending the method to the monitoring of rhodamine 6G, metronidazole, fluoxetine, and enrofloxacin. In this article, SERS-DGT Sensor, a platform for directly on-site sensing of organic DGT, holds great potential for in situ sampling and on-site sensing for a wide range of organics and provides a new idea for environmental monitoring.

Synergistic effects of sequential light treatment with 222-nm/405-nm and 280-nm/405-nm wavelengths on inactivation of foodborne pathogens.

Light-based technologies of different wavelengths can inactivate pathogenic microorganisms, but each wavelength has its limitations. This work explores the potential of sequential treatments with different wavelengths for enhancing the disinfection performance of individual treatments by employing various bactericidal mechanisms. The effectiveness, inactivation kinetics, and bactericidal mechanisms of treatments with 222/405, 280/405, and 405 nm alone against Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium, and Pseudomonas aeruginosa were evaluated. Inactivation experiments were performed in thin liquid bacterial suspensions that were treated either individually with 48 h of 405-nm light or sequentially with (i) 30 s of 222-nm far-UV-C light, followed by 48 h of 405-nm light, or (ii) 30 s of 280-nm far-UV-C light, followed by 48 h of 405-nm light. Survivors were recovered and enumerated by standard plate counting. All inactivation curves were non-linear and followed the Weibull model (0.99 ≥ R2 ≥ 0.70). Synergistic effects were found for E. coli, L. monocytogenes, and S. Typhimurium, with maximum inactivation level increases of 2.9, 3.3, and 1.1 log CFU after the sequential treatments, respectively. Marginal synergy was found for S. aureus, and an antagonistic effect was found for P. aeruginosa after sequential treatments. Significant differences in reactive oxygen species accumulation were found (P < 0.05) after various treatment combinations, and the performance of sequential treatments was correlated with cellular oxidative damage. The sequential wavelength treatments proposed demonstrate the potential for enhanced disinfection of multiple foodborne pathogens compared with individual wavelength treatments, which can have significant food safety benefits. IMPORTANCE Nonthermal light-based technologies offer a chemical-free method to mitigate microbial contamination in the food and healthcare industries. However, each individual wavelength has different limitations in terms of efficacy and operating conditions, which limits their practical applicability. In this study, bactericidal synergism of sequential treatments with different wavelengths was identified. Pre-treatments with 280 and 222 nm enhanced the disinfection performance of follow-up 405-nm treatments for multiple foodborne pathogens by inducing higher levels of cellular membrane damage and oxidative stress. These findings deliver useful information for light equipment manufacturers, food processors, and healthcare users, who can design and optimize effective light-based systems to realize the full potential of germicidal light technologies. The results from the sequential treatments offer practical solutions to improve the germicidal efficacy of visible light systems, as well as provide inspiration for future hurdle disinfection systems design, with a positive impact on food safety and public health.

Numerical simulation of solid–liquid mixing characteristics in a tank stirred by an improved double-layer 4-pitched blades impeller

Abstract Aiming at the problems of low mixing efficiency and poor uniformity of solid–liquid dispersion caused by double-layer 4-pitched blades turbine, a new impeller is obtained by optimizing the structure of the traditional blade. In order to efficiently apply the improved double-layer 4-pitched blades impeller to the mixing process of DNAN-based explosives, this paper takes the new impeller as the research object, investigating the solid–liquid suspension characteristics of the stirred tank through computational fluid dynamics (CFD). A stirring experiment is designed, and a conductivity probe is employed to measure the local solid particle concentration. After validating the CFD model by experimental results, numerical analysis is successfully used to examine the impacts of stirring speed, layer spacing, impeller height from the bottom and impeller inclination angle on the solid–liquid mixing quality. Results show that the increase of rotational speed can significantly enhance the solid–liquid dispersion efficiency. Meanwhile, the blade structure parameters have an important influence on the homogeneity of solid phase distribution, and the appropriate blade structure can make the particles have a better suspension effect. Moreover, the improved blade has obvious advantages in solid–liquid space homogenization in comparison to the traditional blade under the same stirring conditions.

Energy absorption characteristics of thin-walled tube filled with liquid suspension of hollow glass microspheres under axial crushing

The deviation between the high initial peak force and low mean crushing force of thin-walled tubes has significantly limited its energy absorption efficiency. To tackle this challenge, a liquid suspension of hollow glass microsphere (SHGM) is employed as a new type of filling material. The axial crushing behavior of SHGM-filled tubes is evaluated by a series of quasi-static compression and dynamic drop weight impact tests. Results show that the specific energy absorption of the composite tube is increased more than 40 %. The energy absorption efficiency of SHGM-filled tube is increased to 0.65–0.70 compared to that of empty tube (0.37–0.43). This promoted energy absorption performance of the composite tube is due to the much-enhanced SHGM liquid filler-tube wall interaction, which is validated from the increased strengthening coefficient of 4.0. This enhanced filler-tube wall interaction is visualized by using 3D digital image correlation technique. These results demonstrate that the SHGM is a superior filling material for thin-walled structures and facilitate the design of next generation lightweight composite structures for energy absorption purposes.

Antagonistic Strains of &lt;i&gt;Pantoea brenneri&lt;/i&gt; as Plant Protectors

The antagonistic activity of Pantoea brenneri strains against a wide range of phytopathogenic threats was studied. It has been established that the strains are characterized by fungicidal activity against the micromycetes Fusarium sambucinum, F. oxysporum, F. solani, Rhizoctonia solani, Alternaria sp., Ascochyta kamchatica, Colletotrichum coccodes as well as antibacterial activity against the phytopathogen Erwinia amylovora, which causes bacterial burn of fruit trees. It has been shown that the cell suspension and supernatant of the culture liquid of Pantoea brenneri strains suppress Fusarium on potato tubers during storage. Pantoea brenneri strains have been found to be safe for model animals. A conclusion was made about the prospects of using P. brenneri strains as objects for the creation of environmentally friendly plant protection products against phytopathogens.

РАЗРАБОТКА УСТАНОВКИ ДЛЯ ИНАКТИВАЦИИ ЗЕРНА СОИ УЛЬТРАЗВУКОМ

The article considers the theory of the issue of designing an ultrasonic screw plant for processing soybean grain. The authors proposed a device based on a screw mechanism that allows the transportation of bulk cargo in the form of a liquid suspension, ultrasonic treatment, liquid withdrawal and extraction. Ultrasonic processing technology allows accelerating mass transfer processes of inactivation of anti-nutritional sub-stances that reduce the digestibility of protein of leguminous crops. The proposed design of the plant allows intensive processing of grain in the working area and squeezing the suspension to the required parameters. The case has a perforated partition for the first spin, a conical narrowing of the case for the second spin. The time of exposure to the processed suspension is set by changing the angle of the housing and the rotation fre-quency of the screw. In order to intensify the process of ultrasonic grain processing, part of the installation body is equipped with a cable heater that allows increasing the temperature to the required parameters. The installation body is fixed on two racks: fixed and adjustable, with which the angle of inclination of the instal-lation body is adjusted (from 150 to 450). The ultrasonic unit can also be used for washing and disinfection of grain, oilseeds or intensive humidification.

Reduction of aerosol dissemination in a dental area generated by high-speed and scaler ultrasonic devices employing the "Prime Protector".

The use of an external dome aerosol containment device (Prime Protector) is proposed to reduce the spread of particles within the dental office. Hence, the aim of our study was to compare the spread of bioaerosols generated by a High-speed Handpiece (HH) and an Ultrasonic Prophylaxis Device (UPD), with and without the Prime Protector dome (PP) by counting Colony Forming Units (CFU) of Lactobacillus casei Shirota, at different distances on the x and y axis. The PP was located considering the parallelism between the base of the dome and the frontal plane of the simulator, aligning the center of the mouth with the center of the dome. The PP dome measurements are 560.0mm x 255.0mm x 5mm. Petri dishes were placed at 0.5 m, 1 m and 1.5 m respectively. Aerosol generation in the laboratory environment was done three times with the following experimental groups 1) HH, 2) HH-PP, 3) UPD, 4) UPD-PP. Each dental device activation (HH and UPD) had a time frame of 2 minutes on the upper anterior teeth of the dental phantom with a liquid suspension containing Lactobacillus casei Shirota (YAKULT 0836A 0123; 1027F 0407). Air pressure and ventilation were parameterized. No separate high-volume evacuation used, nor was there any air removal attached to the dome. Results showed no significant difference between distance and axis in the CFU count. When means for devices and distances were compared between each of them all showed significant differences except for UPD and UPD-PP (p <0,004). In conclusion, external devices like Prime Protector could help decrease aerosol diffusion during high-speed handpiece activation. However, this dome does not replace the use of PPE inside dental clinics.

Effect of Using Three Bacterial Isolates of Lactic Acid Bacteria Lactobacillus acidophilus 4453, Bifidobacterium bifidum 5144 and Streptococcus thermophilus 5935 as Probiotics on Thyroid Hormones and Liver Enzymes of Common Carp Fingerlings Cyprinus carpio Linnaeus (1758)

This study was conducted to evaluate the efficiency of three bacterial isolates of Lactobacillus acidophilus 4453, Bifidobacterium bifidum 5144, and Streptococcus thermophilus 5935 on thyroid hormones and liver enzymes of common carp fingerlings which had initial body weight attained (44±0.69) g. A total of 72 fish were used and randomly divided into 4 treatments with 3 replicates (6 fish per replicate). An experimental diet was prepared with a crude protein attained (29.14%) and gross energy of 396.726 kcal / g. The bacterial suspensions were prepared at a dilution of 1*10-6 cfu/ml and were added to the suspension of 20% Arabic gum and phosphate buffer salt as an enveloping and adhesive material of bacterial cells to increase their stability and survival on feed pellets. The liquid bacterial suspensions were added to specified amounts of the experimental diets according to the following treatments (T0 control treatment, T1 Lactobacillus acidophilus 4453, T2 Bifidobacterium bifidum 5144, and T3 Streptococcus thermophilus 5935. Thyroid hormones (TSH, T3, and T4) and liver enzymes (AST, ALT, and ALPA) were assessed after 83 days of the experiment. results of the statistical analysis showed that all the bacterial isolates treatments exceeded on T0 of thyroid hormones as T2 followed by T3 and then T1. As for liver enzymes, T0 was significantly exceeded on other treatments of AST, while there was no significant difference among all experimental treatments of ALT. T0 was exceeded on other treatments of ALP, whilst the lowest recorded mean of T3. Here we conclude that the three bacterial isolates treatments in the food of common carp fingerling had a major role in increasing the values of thyroid hormones, and this indicates an increase in the metabolic activities of these fish, and no damage occurred to the liver cells of those fish as a result of the use of the mentioned bacterial isolates.

SiC/YAG composite coatings by a novel liquid fuelled high velocity oxy-fuel suspension thermal spray

Despite recent advances in suspension-based thermal spray techniques, there is still a need to widen the capability of available thermal spray setups to handle suspension to explore new compositions and improve the properties and performance of existing ones. In this work, a novel setup for injecting liquid-based feedstock in a liquid-fuelled high velocity oxy-fuel (HVOLF) thermal spray torch is proposed, involving a new hardware (“Hybrid Nozzle”) capable of injecting suspension radially and protecting the thermal spray flame from the environmental oxygen by inert gas shrouding. The new setup was used to deposit SiC/YAG composite coatings with 85 wt% SiC content, and their wear performance was evaluated. An oxygen deficient environment was provided to the HVOLF flame, ensuring that no or minimal (<2 wt%) SiO2 was formed in the coating during the spray, as confirmed by XRD. A good wear performance was observed at low load below 20 N, with a specific wear rate < 5 × 10−5 mm3/Nm, with the onset of wear mechanisms characteristic of ceramic wear in the brittle regime between 20 and 30 N. The future applicability of this novel setup to a range of oxidation- and heat-sensitive materials and composites offers the opportunity for new coating materials to be explored with suspension and solution precursor-based HVOLF thermal spray.

The structures of two acidic polysaccharides from Gardenia jasminoides and their potential immunomodulatory activities

This study identified two homogeneous acidic polysaccharides from Gardeniae fructus, GJP50–3 and GJP50–4, which exhibited potential immunomodulatory activities in macrophage activation assays, via liquid-chip technology, and in a zebrafish model. Monosaccharide composition analysis and gel permeation chromatography revealed that GJP50–3 and GJP50–4 were composed of Rha, GalA, Glc, Gal, and Ara in specific ratios and had molecular weights of 91.5 kDa and 140.3 kDa, respectively. Based on FT-IR, GC–MS, and NMR analyses, these polysaccharides were identified as typical pectin polysaccharides with methylation degrees of 24.7 % and 21.4 %, respectively. The primary structures of GJP50–3 and GJP50–4 included linear HG domains and branched RG-I domains with arabinans and AG side chains. In vitro, GJP50–3 and GJP50–4 could stimulate NO release and increase the secretion of TNF-α in a RAW 264.7 macrophage model. Luminex liquid suspension chip detection revealed that GJP50–3 significantly promoted the secretion of multiple interleukins [IL-6, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13], TNF-α, and chemokines (G-CSF, GM-CSF, MCP-1 and RANTES). In vivo, these polysaccharides could also increase NO release and neutrophil count in a zebrafish model. These findings suggested that GJP50–3 and GJP50–4 might have the potential to be used as immunomodulators in the food and pharmaceutical industries.

Patterned Nanoparticle Arrays Fabricated Using Liquid Film Rupture Self-Assembly.

Self-assembly is an important bottom-up fabrication approach based on accurate manipulation of solid-air-liquid interfaces to construct microscale structures using nanoscale materials. This approach plays a substantial role in the fabrication of microsensors, nanosensors, and actuators. Improving the controllability of self-assembly to realize large-scale regular micro/nano patterns is crucial for this approach's further development and wider applications. Herein, we propose a novel strategy for patterning nanoparticle arrays on soft substrates. This strategy is based on a unique process of liquid film rupture self-assembly that is convenient, precise, and cost-efficient for mass manufacturing. This approach involves two key steps. First, suspended liquid films comprising monolayer polystyrene (PS) spheres are realized via liquid-air interface self-assembly over prepatterned microstructures. Second, these suspended liquid films are ruptured in a controlled manner to induce the self-assembly of internal PS spheres around the morphological edges of the underlying microstructures. This nanoparticle array patterning method is comprehensively investigated in terms of the effect of the PS sphere size, morphological effect of the microstructured substrate, key factors influencing liquid film-rupture self-assembly, and optical transmittance of the fabricated samples. A maximum rupture rate of 95.4% was achieved with an optimized geometric and dimensional design. Compared with other nanoparticle-based self-assembly methods used to form patterned arrays, the proposed approach reduces the waste of nanoparticles substantially because all nanoparticles self-assemble around the prepatterned microstructures. More nanoparticles assemble to form prepatterned arrays, which could strengthen the nanoparticle array network without affecting the initial features of prepatterned microstructures.

Effects of porous structure on the deformation failure mechanism of cement sheaths for wellbores

The influence and mechanism of porous structure on the deformation failure of cement sheaths under hydraulic pressure is still unclear. To solve this problem, a net slurry cement sheath and a liquid silicon cement sheath were prepared by using a cement material and a liquid silicon suspension. The distributions of the pore radius and spatial location were analyzed using computed tomography scanning and statistics to obtain their probability density distribution functions. Based on the distribution functions, the single-layer and double-layer porous reconstruction models of the net slurry cement sheath and liquid silicon cement sheath were constructed using a FLAC 3D program. A series of numerical simulations were conducted to study the deformation failure of the cement sheaths under in situ stress and hydraulic pressure. The effects of the porous and double-layer structures on the breakdown pressure, plastic failure zone, radial deformation, and stress distribution of the cement sheaths were analyzed. As a result, the mechanisms for the influence of the porous and double-layer structures on the failure mode, failure path, and interaction between the cement sheath and metal casing were revealed. The results of this research provide a theoretical basis for an in-depth understanding of the failure mechanisms of porous cement sheaths.

Measuring the Surface Area Concentration and Specific Surface Area of Mass-Produced Graphene Nanoflakes via Fluorescence Quenching

A primitive cubic lattice composed of 1,000 atoms has 488 surface sites. By definition, every atom in a strictly two-dimensional single-layer lattice composes its surface. These surface atoms are the ones that undergo chemical interactions with the surrounding medium, thereby defining the functionalities of the nanostructure. As such, one of the most important morphological properties of nano-objects is the extremely large specific surface area that enhances their levels of reactivity. Here, we introduce an optical spectroscopy method to measure the surface area concentration, ρA, of mass-produced graphene nanoflakes in liquid dispersions. The information is accessed from the quenching of the fluorescence signal from the dye molecules dispersed in the medium. We found that the quantum efficiency of the fluorescence signal decays exponentially with the concentration of graphene’s surface area, the decay rate being independent of the degree of exfoliation. If the mass concentration ρ is known by other means, the specific surface area can be extracted from the ratio ρA/ρ. The measurements can be performed directly in liquid suspensions of nanoflakes, being highly applicable to the quality control of mass-produced two-dimensional nanomaterials, especially by means of mechanically assisted liquid-phase exfoliation.

Controlling the drying characteristics of suspensions via colloidal interactions: Particle-scale modeling

During drying of colloidal suspensions, evaporation of the suspending liquid drives the formation of concentrated particle layers beneath the receding free surface. The particle layers can lower the drying rate especially when the suspensions contain small nanoparticles. We investigate how such drying characteristics are affected by interactions between particles by use of Langevin dynamics simulations, for which we develop an analytical model to evaluate the decreasing drying rate from the permeation resistance of the formed particle layers. Considering aqueous suspensions where the particles interact through DLVO potentials, we show that there is an ionic strength where the drying rate is the most lowered and that the decrease in the drying rate is remarkably suppressed when the particles aggregate at sufficiently high ionic strength. This behavior reflects the structure of particle layers varied by the interactions. Our result provides an example how to control the drying characteristics by suspension composition.

Wavelength dependence of ultraviolet light inactivation for SARS-CoV-2 omicron variants

Ultraviolet (UV) irradiation offers an effective and convenient method for the disinfection of pathogenic microorganisms. However, UV irradiation causes protein and/or DNA damage; therefore, further insight into the performance of different UV wavelengths and their applications is needed to reduce risks to the human body. In this paper, we determined the efficacy of UV inactivation of the SARS-CoV-2 omicron BA.2 and BA.5 variants in a liquid suspension at various UV wavelengths by the 50% tissue culture infection dose (TCID50) method and quantitative polymerase chain reaction (qPCR) assay. The inactivation efficacy of 220 nm light, which is considered safe for the human body, was approximately the same as that of health hazardous 260 nm light for both BA.2 and BA.5. Based on the inactivation rate constants determined by the TCID50 and qPCR methods versus the UV wavelength, the action spectra were determined, and BA.2 and BA.5 showed almost the same spectra. This result suggests that both variants have the same UV inactivation characteristics.

Feasibility of producing a liquid additive derived from basalt powder for use in the foliar biofertilizer industry

The present work aims to evaluate the technical feasibility of using basalt powder in the form of a liquid suspension for agriculture. The study was conducted in different research environments according to their stages and specific objectives, which are as follows: Unochapecó Soil Laboratory; IBRA-SP Laboratory and the UPF Laboratory (Passo Fundo/RS). The concentrations of basalt rock dust in liquid thermal dilution of organic solution were outlined in a factorial scheme (2x3), with Factor A corresponding to Thermal dilution (ºC) and Factor B being the fraction of basalt dust (g), with 4 replications, totaling 24 plots. The response variables analyzed were: N; P2O5; K2O; Here; mg; S; Zn; Ass; Mn; B; Co; Mo and Fe. The collected data were submitted to descriptive and inferential analysis through the variance by the F test (P≤0.05) and the differences between the means were compared by the Tukey test (P≤0.05). When analyzing statistically in an inferential and descriptive way, the proposed methodology is considered technically efficient for the extraction of macro and micronutrients present in the basalt powder, with emphasis on the hot dilution with 100 ml of solute and 50g of basalt powder.

Domateste Kök Ur Nematodu Mücadelesinde Kitosanın Toprak ve Yaprak Uygulamaları

In this research, the effect of soil, foliar and simultaneous soil+foliar applications of chitosan on gall and egg mass of root-knot nematode Meloidogyne incognita was investigated in tomato plants under controlled conditions (24±1°C, 60±5% RH). Fluopyram (0.16 ml/L) was used as positive control while only nematode-treated plants were considered as negative control. The study was set up in a randomized plot design with 5 replications for each application. The liquid suspension of chitosan diluted at 1% was used. In soil application, 5 ml was applied to each pot by using a graduated cylinder while in foliar application, the liquid suspension at 1% was applied using a portable hand sprayer until the solution was finished. The study was evaluated according to the 1-9 gall and egg mass index 60 days after inoculation of nematodes. The lowest gall (2.8) and egg mass (2.4) indexes were detected in the simultaneous soil+foliar application and took place in the same statistical group with the positive control nematicide. It was determined that the nematicidal effect of chitosan has increased in the case of combined soil and foliar applications. These results support the fact that chitosan applications are successful in the control of root-knot nematode.

LGG-09. CLINICAL ACTIVITY OF PAN-RAF INHIBITOR TOVORAFENIB IN THE REGISTRATIONAL PEDIATRIC LOW-GRADE GLIOMA ARM OF THE PHASE 2 FIREFLY-1 (PNOC026) STUDY

Abstract Genomic alterations of BRAF are common oncogenic drivers in pediatric low-grade glioma (pLGG). Tovorafenib is an investigational, oral, selective, brain-penetrant, small molecule, type II panRAF inhibitor. FIREFLY-1 (NCT04775485) is a multicenter phase 2 study evaluating the efficacy and safety of tovorafenib monotherapy in patients with BRAF-altered cancers. Registrational arm 1 includes patients 6 months-25 years of age with recurrent or progressive LGG previously treated with ≥1 prior line of systemic therapy. Tovorafenib 420 mg/m2 (≤600 mg) is administered weekly, in 28-day cycles, (tablet or liquid suspension formulation) until progression. The primary endpoint of arm 1 is ORR, as defined by RANO criteria and determined by blinded independent review. As of September 28, 2022, arm 1 had enrolled 77 patients and is fully accrued. All patients had ≥6 months of follow-up. Median age at enrollment was 8 years (range 2-21). Patients had received a median of 3 prior lines of systemic therapy (range: 1-9); 60% had received prior MAPK pathway-targeted agents. The most common tumor site was optic pathway (51%). Sixty-four patients harbored a tumor BRAF fusion/rearrangement (83%) and 13 (17%) a V600E mutation. Median duration of tovorafenib treatment is 8.4 months (range 0.7-16.8); 59 patients (77%) remained on treatment at data cutoff. ORR in 69 RANO-evaluable patients was 64%, [3 CR, 41 PR (10 unconfirmed) and 19 SD] with a clinical benefit rate of 91%. The most common treatment-related adverse events (TRAEs) of any grade were hair color changes (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular rash (42%). Two patients (3%) discontinued tovorafenib due to TRAEs. Updates from a longer follow-up on the 77 patients in arm 1 will be presented. Tovorafenib was generally well tolerated and showed encouraging evidence of antitumor activity in children and young adults with refractory BRAF-altered LGG.

LOGGIC/FIREFLY-2: A phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration.

TPS10067 Background: Pediatric low-grade gliomas (pLGGs) are the most common CNS tumors of childhood. Genomic alterations of BRAF are oncogenic drivers in almost all pLGGs. Approximately 50%‒60% of pLGGs harbor a KIAA1549-BRAF fusion and 5%‒15% a BRAF V600E mutation. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan-RAF inhibitor. The registrational, phase 2 FIREFLY-1 (NCT04775485) study of tovorafenib in pediatric patients with recurrent/progressive LGG is ongoing and interim analysis has shown encouraging anticancer activity. Methods: LOGGIC/FIREFLY-2 (NCT05566795) is a registrational, 2-arm, randomized, multicenter, global (~100 sites across Australia, Canada, Europe, New Zealand, Singapore, South Korea, and USA), phase 3 trial being conducted in collaboration with the SIOPe Brain Tumor Group LOGGIC Consortium. The study is evaluating the efficacy, safety, and tolerability of tovorafenib vs. standard of care (SoC) chemotherapy in patients &lt; 25 years old with pLGG harboring an activating RAF-alteration and requiring first-line systemic therapy. Approximately 400 patients will be randomized 1:1 to receive oral tovorafenib, 420 mg/m2 (≤600 mg) once weekly (tablet or liquid suspension), or an investigator’s choice of SoC chemotherapy: COG-V/C regimen (60 weeks), SIOPe-LGG-V/C regimen (81 weeks), or single-agent vinblastine (70 weeks). Tovorafenib will be continued until the occurrence of radiographic progression (based on Response Assessment in Neuro-Oncology [RANO] criteria as determined by the investigator and confirmed by independent review) or unacceptable toxicity; patients with radiographic progression may be allowed to continue tovorafenib if, in the opinion of the treating investigator, they are deriving clinical benefit from study treatment. Patients who progress in the SoC arm during or after completion of chemotherapy are eligible to cross-over to receive tovorafenib. The primary endpoint is the objective response rate based on RANO criteria, as determined by independent review. Key secondary endpoints are progression-free survival and duration of response per RANO criteria by independent review and overall survival. Other secondary endpoints include efficacy assessments per Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria, changes in neurological and visual function, and safety and tolerability. Exploratory endpoints include efficacy assessments per investigator, tumor volume, adaptive behavior and quality of life. Prognostic and predictive molecular biomarkers, including senescence profiles for treatment outcome, response prediction, and treatment resistance, will be explored in parallel studies. Clinical trial information: NCT05566795 .