Panel Scores Research Articles

Exploring delamination behavior in carbon nanofiber-reinforced sandwich structures with various corrugated cores: An experimental study on mixed-mode crack growth

In this paper, the delamination behavior between the face sheet and core of sandwich panels under a mixed mode of failure during TPSB (Three-Point Sandwich Beam) testing is investigated. The experiments were conducted on two sets of specimens: one reinforced with 0.25% carbon nanofiber weight and the other consisting of samples without carbon nanofibers. The core of the sandwich structures was made of PVC foam, and the corrugated cores and face sheets were made of glass-epoxy fibers. The investigated specimens had corrugated cores with different geometries, such as trapezoidal, square, and triangular. The Force-Displacement and R-CURVE diagrams of sandwich panels reinforced with and without carbon nanofibers were extracted. The strain energy release rate increased with increasing crack length, and this trend in the mixed mode of failure was generally upward. The strain energy release rate in the sandwich panel reinforced with carbon nanofibers with trapezoidal, square, and triangular corrugated cores increased by 20.7%, 39.8%, and 44.6%, respectively. These findings underscore the potential of carbon nanofiber-reinforced sandwich structures for diverse applications requiring enhanced fracture resistance under varying loading conditions. These structures have many applications in wind turbine blades and aerospace industry.

Topology optimization based on the improved high-order RAMP interpolation model and bending properties research for curved square honeycomb sandwich structures

Curved honeycomb sandwich structures with larger surface areas effectively reduce the number of fasteners and connectors, resulting in weight reduction, cost savings, and reliability improvement. Square honeycombs exhibit higher in-plane tensile strength, and are more compatible with mechanical components. Topology optimization can realize the variable-density design of square honeycombs, enhancing the strength and stiffness of curved sandwich structures, but the high-order Rational Approximation of Material Properties (RAMP) interpolation model with a fast convergence rate has the relatively poor clarity and stability in topology boundaries. Hence, a variable-density topology optimization method based on the improved high-order RAMP model is developed for curved square honeycomb sandwich structures. The high-order RAMP interpolation model is improved by incorporating a minimum modulus term into the material interpolation function and employing the Bi-directional Evolutionary Structural Optimization (BESO) to refine the Optimality Criteria (OC) method. A functional relationship between the wall thickness of cross-shaped cells (i.e., simplified models of four adjacent square cells arranged in a cross) and the relative density of topology units is constructed using a density mapping method, and the topology optimization with the relative density of cross-shaped cells as the design variable is performed to minimize the compliance of the core. Three-point bending tests are conducted on 3D printed non-optimized and optimized curved honeycomb sandwich structures with different core material retention rates and panel thicknesses, and the experimental results are compared with those of simulations to explore the bending properties and failure behaviors. The results indicate that the modified high-order RAMP interpolation model enhances the clarity and stability of topology structures, the variable-density topology optimization significantly improves the bending properties of curved square honeycomb sandwich structures, and the experimental and numerical results are largely consistent.

A semi-analytical model for predicting the shear buckling of laminated composite honeycomb cores in sandwich panels

Laminated composite honeycomb cellular core sandwich panels are widely utilized in various industries due to their exceptional stiffness-to-weight ratio and strength characteristics. Current analytical models often simplify honeycomb cores as homogenized continua, effectively predicting stiffness but falling short in capturing crucial failure modes, particularly shear buckling of honeycomb core walls. Existing theoretical studies on shear buckling are limited to isotropic materials and specific honeycomb geometries. While numerical models can simulate cell wall buckling, their computational demands render them impractical for large structures employing sandwich panels. This paper introduces a novel, simplified semi-analytical approach that accurately predicts the shear buckling load of laminated composite honeycomb cellular cores. The model accounts for bend-twist coupling effects and rotational restraints at laminate wall boundaries. To validate the proposed approach, predictions are compared with finite element analysis results for hexagonal honeycomb cores and cores of varying shapes, incorporating diverse fibre lay-up configurations. The findings demonstrate excellent agreement between the proposed approach and finite element analysis, indicating its reliability in predicting shear buckling. This research addresses the gap in existing methodologies by offering a practical and efficient tool for predicting shear buckling in laminated composite honeycomb cores, extending applicability beyond isotropic materials and specific honeycomb geometries. The proposed approach holds promise for optimizing the design and structural integrity of sandwich panels, impacting industries relying on these lightweight and high-performance structures.

Enhancing performance of sandwich panel with three-dimensional orthogonal accordion cores

This study introduces a novel three-dimensional orthogonal accordion structure (3D-OAS) as the cellular core of sandwich panels, achieving multi-directional zero Poisson’s ratio through the orthogonal combination of two-dimensional accordion structures. To analyze its static characteristics effectively, a two-dimensional equivalent Reissner–Mindlin model (2D-ERM) was established utilizing the variational asymptotic method (VAM). The accuracy of 2D-ERM was confirmed by conducting three-point bending tests on 3D-printed specimens and analyzing the in-plane and out-of-plane deformation results of the 3D finite element model (3D-FEM). The comparison of global displacement contours and path-displacement curves between 3D-FEM and 2D-ERM showed a high level of agreement in predicting static deformation. The equivalent stiffness of SP-3D-OAS steadily increased as the inclined angle deviates by 90-degree, irrespective of whether it pertains to the convex or concave angle. Evaluation of deformability in sandwich panels with different cellular core forms revealed superior comprehensive performance in 3D-OAS, followed by 3D-YRS and 3D-XYAS, with a reduction of 16.41% and 17.35% in specific stiffness, respectively. Compared to the 3D-FEM, 2D-ERM significantly reduces computation time without compromising engineering accuracy. The research results provide a useful reference for optimal design of sandwich panels with multi-directional ZPR cellular core.

Shape memory sandwich structure with reprogrammable shape and mechanical properties

Sandwich structures are usually used in aerospace and automotive engineering fields. By selecting different core materials and panels, a large number of design strategies are proposed to obtain various types of sandwich structures for various applications. Here, we developed a kind of shape memory sandwich structure using shape memory foam and laminates. The sandwich structure can not only program its shape utilizing SME but also can adjust its mechanical properties by controlling its temperature or shape. The mechanical and thermal–mechanical properties of shape memory laminates, foam and sandwich structure were characterized, respectively. The energy absorption property and bending resistance of the shape memory sandwich structure after being programmed were studied by compression test and drop weight impact test. Shape programmable and mechanical properties adjustable suggest potential applications of this sandwich structure in an adjustable shock-absorbing interface and space deployable structure.

Constructing a Large Language Model to Generate Impressions from Findings in Radiology Reports.

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum

BackgroundDrought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses.ResultsTaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance.ConclusionsTaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

Numerical modeling of composite spherical-roof contoured core (SRCC) sandwich panels subjected to blast loading

This article investigates the blast response of spherical-roof contoured core (SRCC) and novel spherical-roof contoured core (NSRCC) sandwich panels under blast loading, which involves the core design and material types. Due to the practical difficulties associated with investigating explosive materials and replicating blast loads, finite element (FE) modeling is a favorable method as a functional and convenient alternative. FE models are established under different charge masses of used trinitrotoluene (TNT), which is used in aluminum (AL) and carbon fiber-reinforced plastic (CFRP) cores of sandwich panels. The Johnson-Cook model and the user-defined material subroutine (VUMAT) predicted the blast performance of AL and CFRP materials on SRCC and NSRCC types with three patterns. The results showed that as the mass of TNT increased from 1 kg to 3 kg, the internal energy was also linearly increased. It was shown that the NSRCC type provided higher internal energy than the SRCC type. The maximum internal energy was shown on the NSRCC2 pattern, which was 41.20 kJ with 3 kg TNT. Moreover, SRCC pattern 1 with AL material provided the minimum deflection compared with the other five patterns. It was indicated that SRCC pattern 1 showed better blast protection performance on 1, 2, and 3 kg TNT. It is highlighted that the SRCC with two patterns can have potential applications on protective structures under blast loading.

Compressive Performance of the PVC Foam Materials used as Sandwich Panel Core

PVC foam materials are preferred in many engineering applications because of their lightweight nature and strength/weight ratio. They are mainly used as the core material in the middle of sandwich panels with improved flexural rigidity. The mechanical performances of sandwich panels, such as flexural load-deflection, core shear load, core shear failure load, and indentation failure load, directly depend on the mechanical properties of the core material. In this study, compression tests of AIREX C70 PVC foams with three different densities were performed. The elastic modulus and strength results obtained from the compression tests were compared with the mechanical properties provided in the dataset supplied by the material manufacturer. The core yield loads of a concept sandwich panel were then obtained using the compression mechanical properties of the core, which were obtained from datasets and experimental results. When the core yield loads obtained using both data were compared, it was revealed that the load obtained using the dataset data was 23% inaccurate. Thus, the study explained why compression tests are necessary even though the mechanical properties of PVC foam materials are known in the datasheet.

Analytical and numerical analysis on local and global buckling of sandwich panels with strut-based lattice cores

Additive manufacturing (AM) offers new possibilities to fabricate and design lightweight lattice materials. Due to the superior mechanical properties of these lattice structures, they have the potential to replace honeycombs as cores in sandwich panels. In addition to the advantage of the integral fabrication thanks to AM, additively manufactured lattice core sandwich panels may be also used as heat exchangers, enabling a multifunctional use of the core. To ensure a reliable and safe structure, the mechanical response of lattice core sandwich panels under given load conditions must be predictable. In conventional sandwich panels subjected to compressive loads, the sandwich’s global buckling and the face sheets’ local buckling are the dominant failure modes. In constrast, core strut buckling may be the critical failure mode in lattice core sandwich panels. Therefore, an analytical 2D model to predict the local buckling of lattice core struts is considered in this study. Furthermore, the critical load for global buckling is obtained based on the first-order shear deformation theory. Thus, the transition from local buckling to global buckling depending on the length-to-thickness ratio is captured by the presented model. The comparison with finite element modeling of the sandwich model with truss cores has proved the accuracy of the derived model.

Fatigue performance of composite-steel injected connectors at room and elevated temperatures

The integration of Glass Fibre-Polymer composite (a.k.a. GFRP) deck panels in bridge infrastructure is hindered by lacking a robust connection technology. A promising bolted connection, utilising injected steel reinforced resin (iSRR) material, has demonstrated lower creep deformation and sustained significantly more shear load cycles than conventional bolts. Nonetheless, the production and testing conditions in all prior experimental campaigns followed idealized lab set-ups. This study bridges the gap between laboratory conditions and the challenges arising during connector’s fabrication under representative conditions, coupled with cyclic load testing at room and elevated temperatures. The iSRR connectors design is modified and tested in actual composite sandwich web core panels, revealing excellent fatigue performance. The statistical analysis yielded F-N curves for shear performance of the connectors that can be used in the design. The slopes of the F-N curves of − 6.6 and − 5.8 were found at room and elevated temperatures, respectively. Finally, with post-cyclic static tests displaying significant connectors’ residual stiffness, resistance, and ductility, the research provides a step forward in enabling the integration of glass fibre composite deck in infrastructure.

Prognostic significance of ctDNA mutation analysis in patients with HER2-positive breast cancer undergoing neoadjuvant chemotherapy.

e12654 Background: Neoadjuvant chemotherapy (NACT) combined with dual anti-HER2 agents followed by surgical resection is the standard treatment for stage II-III HER2- positive breast cancer (BC). Despite the availability of effective therapies such as ado-trastuzumab emtansine (T-DM1) and neratinib, identifying patients at high risk of disease recurrence remains challenging. To evaluate whether circulating tumor DNA (ctDNA) can be used as a biomarker to assess treatment response in patients with HER2-positive EBC treated with neoadjuvant anti-HER2 therapy. ctDNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in EBC patients. This study aimed to assess the role of ctDNA mutation analysis using low-pass whole-genome sequencing (lpWGS) and whole exome sequencing (WES) in evaluating blood copy-number burden (bCNB), genomic alterations, mutational signatures, blood tumor mutational burden (bTMB), and minimal residual disease (MRD) monitoring. Methods: A total of 46 HER2-positive BC patients who underwent NACT combined with dual anti-HER2 agents and surgical resection were enrolled, including 28 clinical stage II and 17 III patients. Plasma samples were collected at four time points: before NACT, after 3 cycles, at the completion of NACT, and after surgery. lpWGS was utilized to assess bCNB, while WES was performed to evaluate genomic alterations, mutational signatures, and bTMB. Mutations selected from the baseline sample were monitored for MRD. In cases where lpWGS yielded negative results, targeted NGS sequencing was conducted. Somatic mutations are identified by whole exome sequencing across 20,000 genes (with boosted sequencing coverage for 600 cancer-related genes). Between 4-50 personalized somatic mutations or fusions are selected for each patient. This personalized panel together with a fixed MRD core panel is utilized for MRD detection and monitoring. Results: Among the enrolled patients, nodal metastasis was observed in 29 patients and 29 were hormone receptor-positive, and 36 achieved pCR (78.2%). Positive ctDNA was detected 58.8% of patients. Higher nodal stage was associated with ctDNA positivity at baseline. MRD positivity after chemotherapy was observed in 4 patients and 2 patients achieved pCR TP53 was the most frequently altered gene, followed by PIK3CA, MAP3K1, REV3L, MYC, MAP2K4, ERBB3, ATRX, ATM and ALK. This pattern is comparable to that observed in previous studies on BC. Non-PCR patients commonly exhibit MAP3K1 and MAP2K4 alteration is their ctDNA. Conclusions: The identification of MRD, regardless of pCR status, can be valuable for risk stratification and personalized treatment decision-making. Further studies are warranted to validate these findings and explore the clinical implications of ctDNA mutation analysis in HER2-positive BC management.

Study on submergence tolerance of rice (Oryza sativa L.) in a core panel of North-East India using GWAS

Rice (Oryza sativa L.) being the major food crop of the north-eastern region, combating floods in rice fields for higher economic yield is a major challenge. A core panel, consisting of local rice landraces that have been cultivated in the flood-prone areas of this region for years, was used for this GWAS study to uncover possible genetic resistance sources to submergence. A study on GWAS was conducted to understand the mechanism of resistance of rice under water-submerged conditions through higher expression of genes. The GWAS analysis of a core panel of 400 rice landraces generated 38,723 filtered SNPs. The result showcased nine loci across the 12 rice chromosomes, one locus each in chromosome 2 and 4, five loci in chromosome 6, and two loci in chromosome 9. The two promising loci among these nine identified loci codes for zinc fingers, C3HC4 type domain-containing proteins, with FDR adjusted p-values of 0.04 each and allele effect of 4.60 and 4.57, respectively. These GWAS-identified association signals are a valuable source for allele mining and can be validated and introgressed into elite germplasms to decipher submergence tolerance in future breeding programs.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Global modified-Delphi consensus on comorbidities and prognosis of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A-related disorders. A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree. Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE. Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.

In-plane and out-of-plane compressive properties of regular and graded cellular cores of sandwich panels fabricated by additive manufacturing

Cellular materials with a gradient of properties become appealing as cores of the sandwich panels due to the possibility of improving strength and absorbed energy in lightweight components. 2D cellular structures designated by honeycombs have an anisotropic behaviour when loaded under in- and out-plane. Thus, when proposing new designs, it is essential to analyse how the in-plane arrangement with a gradient in cell wall thickness affects in-plane and out-of-plane mechanical properties. This work aims to study graded cellular structures in comparison with regular hexagonal honeycombs. Structures were manufactured by laser powder bed fusion using an aluminium alloy. Regular arrangements were formed with cells with the same thickness, while graded structures possessed a radial gradient of cell thickness. Three types of innovative gradients, where cell length varies radially along concentric layers, were analysed. The compressive properties of regular and graded structures were evaluated when loaded both under in-plane and out-of-plane conditions. Compression behaviour was assessed, both experimentally and by numerical modelling. Even though there is a mismatch between numerical and experimental results, they exhibit the same trends. All graded samples showed an increased mechanical performance when loaded under out-of-plane conditions in comparison with the results from tests under in-plane loading with values, for example, of stiffness four hundred times larger, absorbed energy around thirty times higher and with yield stress four times larger. The results showed that the graded samples attain higher values of strength, stiffness and absorbed energy in comparison with regular hexagonal honeycombs, for the same relative density.

Aeroelastic analysis of a lightweight topology-optimized sandwich panel

Sandwich structures with lattice cores are novel, lightweight composite structures and are widely used in the aerospace industry. Besides, the aeroelastic behavior of sandwich panels in a supersonic flow regime still needs to be thoroughly studied. This work investigates the supersonic flutter of a sandwich panel whose core is topology-optimized. A finite element model of a sandwich panel based on the layerwise theory, coupled with the first-order piston theory, is presented. The sandwich panel core is assessed using a topology optimization approach with flutter loading constraints. The subsequent analytical homogenization scheme is developed to provide the equivalent mechanical properties of the topology-optimized panel. The modeling approach is fully validated, and the results demonstrate that the sandwich panel is capable of enlarging the flutter-free operational flight range when compared with other conventional panel designs. A parametric analysis of the topology-optimized sandwich panel regarding the critical flutter conditions is performed.

Abstract PO5-16-04: Tissue-informed personalized MRD detection assay may outperform tumor-informed fixed panel strategy in Triple Negative Breast Cancer (TNBC)

Abstract Background: Minimal residual disease (MRD) detection by ctDNA analysis enables identifying patients with high recurrence risk and refining risk stratification to guide treatment selection precisely, which may improve patient survival or avoid overtreatment. We previously developed a 1021-gene fixed panel MRD detection assay, MNavigator V1, demonstrating high prognostic evaluation value in various solid tumors, including lung cancer, colorectal cancer, and esophageal carcinoma, and relevant research results have been published. Recently, the assay upgraded to MNavigator V2, a customized patient-specific panel strategy to ultra-deep sequencing, with higher clinical performance and more economical. Here, we head-to-head compared the performance of MNavigator V1 with V2, using the same collection of blood samples from TNBC patients. Methods: The retrospective study recruited 48 patients diagnosed with stage II~III TNBC with adequate samples (NCT04501523/NCT04803539). Five patients in the cohort received neoadjuvant therapy (Neoad-group), and the standard treatment regimen of the remaining 43 patients was adjuvant therapy (ad-group) after surgery. The surgical tumor tissue of all these patients was collected. Peripheral blood samples were collected at various time points, baseline samples before neoadjuvant therapy, 7-day after neoadjuvant therapy, 1-month postoperative, 7-day after adjuvant therapy, and subsequent every 3~6 months follow-up. The personalized, tumor-informed MRD detection approach MNavigator V2 started by identifying somatic mutation of the resected tumor with a 1021-gene panel covering 1.6Mb of the human genome. Then, a customized panel consisting of up to 20 top-ranked patient-specific somatic variants was designed. After that, unique molecular identifiers (UMI) based 100,000X ultra-deep next-generation sequencing on plasma samples was conducted by adopting the mix panel of the patient-specific panel and a 5kb breast cancer universal core panel. MNavigator V1 assay, a fixed panel assay also applied the same off-the-shelf 1021-genes panel with a sequencing depth of 10,000X to detect MRD of blood samples. Results: Until May 2023, the median follow-up time of 660 days, and 8 patients were recurrence confirmed by CT imaging. The median tracked tissue-informed mutations was 7 (2~18). In this study, the screening time point was defined as the combined MRD status of the blood samples collected before and after neoadjuvant therapy, and 1-month post-surgery for the Neoad-group, as for the ad-group, the time point referred to 1-month post-surgery and post-adjuvant therapy. If any one of these time nodes' MRD was positive, the screening period MRD was positive. During the screening period, MNavigator V1 and V2 accurately predicted 6/8 (75.0%) recurrence. MRD-positive status was associated with a worse prognosis, compared to the MRD-negative population, with hazard ratios of 9.0 and 19.9 for V1 and V2 assay, respectively. The longitudinal MRD evaluation yield a higher sensitivity of 7/8 (87.5%) for recurrence prediction with MNavigator V2 at a median lead time of 104 days, whereas the V1 assay predicted 6/8 (75.0%) at 94 days, and the hazard ratio was 40.4 vs 8.5. In one brain-only metastasis patient, MRD was undetectable, which may be due to the limitation of the blood-brain barrier. For recurrence-free patients with 1 year of follow-up, 92.5% (37/40) were MRD-negative with MNavigator V2 assay. These three patients who detected MRD-positive after surgery, ctDNA cleared after adjuvant therapy, and persistently negative during follow-up, may benefit from treatment. Conclusion: Based on the patient-specific tumor mutation profile, the personalized MRD detection assay achieved better clinical performance than the fixed panel strategy. Citation Format: Shunying Li, Wei Gao, Ning Fu, Wuqiang Cao, Xiaoling Zeng, Xinhua Du, Qiang Liu. Tissue-informed personalized MRD detection assay may outperform tumor-informed fixed panel strategy in Triple Negative Breast Cancer (TNBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-04.

Pharmacogenomic Predictors of Antibiotic-Associated Drug-Induced Liver Injury in Critically Ill Children: Observational Study Results

INTRODUCTION. The pathogenesis of antibiotic-associated drug-induced liver injury (DILI) in children has not been fully elucidated to date. Certain genotypes in patients increase the probability of developing DILI. Therefore, the identification of pharmacogenetic markers associated with DILI in children is essential.АIM. This study aimed to identify pharmacogenetic biomarkers of new-onset DILI associated with tigecycline and meropenem in children.MATERIALS AND METHODS. This prospective observational study was conducted in the Morozov Children’s City Clinical Hospital from 1 February 2020 to 1 September 2021. The study analysed the incidence and types of antibiotic-associated adverse drug reactions (ADRs) in 100 critically ill children aged 0 to 17 years (44 boys and 56 girls). Pharmacogenetic testing was performed in children with ADRs (n=30) to identify potential mechanisms involved in the development of their ADRs. The authors isolated and tested DNA from buccal epithelium swabs using the Agena Bioscience iPLEX® PGx Pro-based VeriDose® Core Panel covering 68 single nucleotide polymorphisms (SNPs) or short insertions and deletions (INDELs) and 5 copy number variants (CNVs).RESULTS. The odds of developing DILI associated with meropenem and tigecycline were higher in carriers of the homozygous cytochrome genotype CYP3A5*3/*3 (OR: 12.6; 95% CI: 1.9–79.4, r=6.54, p=0.011) than in patients with the heterozygous genotype CYP3A5*1A/*3. The odds were even higher in patients not carrying the CYP3A5*1A/*3 genotype (OR: 17.14; 95% CI: 1.79–16.3, r=6.24, p=0.013). The detection of the CYP3A5*3/*3 ge­notype had a prognostic accuracy of 76.7%, a sensitivity of 82%, and a specificity of 74% in predicting the risk of DILI associated with meropenem and tigecycline. Moreover, children with DILI carried the heterozygous ge­notype SLCO1B1*1/*5 (rs4149056 polymorphism) more often than children with other adverse reactions ­associated with meropenem and tigecycline (r=9.8, p=0.002).CONCLUSION. The results of this study prove the prognostic significance of the homozygous cytochrome genotype CYP3A*3/*3 as an indicator of a potential risk for developing DILI associated with meropenem and tigecycline in children in critical conditions.The study was registered at ClinicalTrials.gov under No. NCT04141657 on 24 October 2019.

Pull-Through Behavior of Novel Additively Manufactured Sandwich Composite Inserts.

Joining structural components with mechanical fasteners is common in many engineering applications across all industries. This study investigates combining additive manufactured inserts with sandwich composites consisting of aluminum honeycomb cores with carbon fiber reinforced facesheets. The combination of these components offers an integrated, lightweight solution when mechanically fastening sandwich composite components using bolted joints. The experimental and numerical investigation explores the influence insert geometry has on the structural response of a sandwich composite under pull-through load scenarios. Various failure modes are observed during experimental analysis with facesheet debonding being the initial failure mode. In addition, finite element models investigate the stress fields in the honeycomb core and overall panel deflections, validating the mechanics observed experimentally. When comparing additively manufactured inserts to standard inserts, additively manufactured inserts have increases in stiffness, maximum force, and total energy absorption of 7.1%, 53.0%, and 62.3%, respectively. These results illustrate the potential of an integrated approach to mechanical joint technology by combining additively manufactured inserts with sandwich composite components using aluminum honeycomb cores.