Size Grade Research Articles

Eyelid Skin Grafting in Young Patients with Facial Nerve Palsy.

Background: The aim of this study is to report outcomes of eyelid full-thickness skin grafting augmentation in facial nerve palsy (FNP) patients younger than 50 years of age. Methods: In a retrospective, consecutive case series, nine eyelid skin grafts performed on eight FNP patients with skin contraction (five females; median age 42 years [range, 17-47]) are presented. In most cases, upper eyelid skin grafting was combined with levator recession and anterior lamellar repositioning. Lower eyelid skin grafting was combined with lower retractors recession in all cases. Functional and cosmetic outcomes were measured preoperatively and at early (1-3 months), intermediate (3-6 months), and late (≥12 months) follow-up. Results: The corneal score improved at early follow-up (p = 0.03) and remained improved at late follow-up (p = 0.042). The gentle closure lagophthalmos was improved at late follow-up (p = 0.042). (p = 0.048). The grades of graft color, edge/skin interface, and size improved at 3-6 months post-grafting and remained improved at late follow-up (p < 0.05). Over the follow-up, four patients (50%) were recommended to have further surgical procedures. Conclusions: The preliminary results from this small cohort suggest that eyelid skin grafting is a viable option for young patients prioritizing cosmesis. This technique warrants consideration for its functional benefits.

Relation of bubble size, grade and recovery in the copper flotation systems

In recent years, studies have shown that bubble structure, which is affected by reagent types, dosages, and particle size, is closely related to flotation performance. In contrast to two-phase systems, there is very limited information regarding bubble size in three-phase systems. To this aim, we investigated the relationship between bubble size and flotation performance with two different copper ores. Firstly, the surface tension and bubble size measurements were carried out in two-phase systems with Methyl isobutyl carbinol, and Polypropylene glycol methyl ether. Then the bubble size measurements were performed in three-phase systems at laboratory and industrial scales. The results showed that surface tension decreased with higher frother amounts and higher pHs. Although remarkable decreases in bubble size were observed with increasing frother amount, a direct relationship between surface tension and bubble size was not observed. However, pH affected the behavior of the frother, resulting in smaller bubble sizes at pH 12 compared to pH 7. Similarly, the three-phase laboratory tests showed that higher amount of frother caused a reduction in the bubble size and the copper grade. Increasing the amount of collector also caused the bubble size and copper grade to decrease, but the frothers were more effective in bubble size reduction. Compared to the two-phase, in the three-phase study bubble size was notably bigger due to the presence of a collector and solid. In the plant scale, smaller bubble size and higher grade were obtained compared with the laboratory scale due to presence of cleaning circuit measurements. The froth phase properties were also affected by the ore types due to properties such as size and hydrophobicity of the various mineral species present.

High CASC expression predicts poor prognosis of lung cancer: A systematic review with meta-analysis.

The long non-coding RNA cancer susceptibility candidate (CASC) has abnormal expression in lung cancer tissues and may correlate with lung cancer prognosis. This study aimed to comprehensively evaluate the association between CASC expression and the cancer prognosis. PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure databases were searched until April 1, 2023, to obtain the relevant literature. Studies that met the predefined eligibility criteria were included, and their quality was independently assessed by 2 investigators according to the Newcastle-Ottawa Scale (NOS) score. Detailed information was obtained, such as first author, year of publication, and number of patients. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted and grouped to assess the relationship between CASC expression and cancer prognosis. The dichotomous data was merged and shown as the odds ratio (OR) with a 95% CI was extracted to assess the relationship between CASC expression and clinicopathological parameters. A total of 12 studies with 746 patients with lung cancer were included in the meta-analysis. The expression levels of lncRNA CASC2 and CASC7 were decreased, while those of CASC9, 11, 15, and 19 were induced in lung cancer tissues compared with paracancerous tissues. In the population with low CASC expression (CASC2 and CASC7), high CASC expression indicated a good lung cancer prognosis (HR = 0.469; 95% CI, 0.271-0.668). Conversely, in the population with high CASC expression (CASC9, 11, 15, and 19), high CASC expression predicted a poor lung cancer outcome (HR = 1.910; 95% CI, 1.628-2.192). High CASC expression also predicted worse disease-free survival (DFS) (HR = 2.803; 95% CI, 1.804-6.319). Combined OR with 95% CI revealed an insignificant positive association between high CASC expression and advanced TNM stage (OR = 1.061; 95% CI, 0.775-1.454), LNM (OR = 0.962; 95% CI, 0.724-1.277), tumor size (OR = 0.942; 95% CI, 0.667-1.330), and histological grade (OR = 1.022; 95% CI, 0.689-1.517). The CASC expression levels negatively correlate with lung cancer prognosis. Therefore, CASC expression may serve as a prognostic marker and a potential therapeutic target for lung cancer.

Migration trajectories and blocking effect of the fine particles in porous media based on particle flow simulation

The particle flow code method based on the discrete element method was used to establish the seepage migration model of fine particles [fine particles (FPs), i.e., suspended particles] in a porous medium. A series of numerical simulations were carried out by changing the particle size, seepage velocity, particle injection number, and wide particle size gradation. The research showed that large FPs play a major role in blocking porous medium channels when the injected FPs have a wide size gradation. Due to the blocking effect, small FPs that would not otherwise have deposited also deposit. Moreover, by increasing the number of large FPs in the mixed particles, the total number of particles deposited and the number of smaller FPs deposited will also increase. The distribution of FPs in porous mediums can be divided into three types: surface deposition, internal deposition, and non-deposition. When the seepage velocity increases and reaches a seepage threshold, which is the critical seepage velocity, the deposited FPs will once again be in a suspended state and undergo migration. On the contrary, the FPs will continue to maintain their sedimentary state, and the critical seepage velocity will also increase correspondingly with increasing particle size.

Surgical treatment and prognosis analysis of hilar cholangiocarcinoma

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery.

In this research, we delved into the predictive potential of three key markers - the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and Onodera's prognostic nutritional index (OPNI), in assessing lymph node metastases in breast cancer patients who had internal mammary lymph node involvement following thoracoscopic surgery. Our study revealed notable pathological distinctions between the groups with and without metastases, while age, tumor size, and histological grade exhibited no significant differences. The analysis unveiled statistically significant variances in NLR, SII, and OPNI when comparing these two groups. Multivariate analysis pinpointed NLR (OR = 1.503), SII (OR = 1.987), and OPNI (OR = 0.612) as robust predictors of lymph node metastases. Remarkably, combining these markers (AUC: 0.897) substantially enhanced the precision of predicting lymph node metastases compared to individual measurements (NLR: 0.749, SII: 0.717, and OPNI: 0.787). In conclusion, this study underscores the pivotal role of NLR, SII, and OPNI in predicting lymph node metastasis among breast cancer patients with internal mammary lymph node involvement post-thoracoscopic surgery, affirming our utility as reliable independent predictors of this critical clinical outcome.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway

BackgroundThe leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. MethodsClinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. ResultsLGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. ConclusionsLGR4 promotes HCC progression via Wnt/β-catenin signaling pathway.

Prediction of constrained modulus for granular soil using 3D discrete element method and convolutional neural networks

To efficiently predict the mechanical parameters of granular soil based on its random micro-structure, this study proposed a novel approach combining numerical simulation and machine learning algorithms. Initially, 3500 simulations of one-dimensional compression tests on coarse-grained sand using the three-dimensional (3D) discrete element method (DEM) were conducted to construct a database. In this process, the positions of the particles were randomly altered, and the particle assemblages changed. Interestingly, besides confirming the influence of particle size distribution parameters, the stress-strain curves differed despite an identical gradation size statistic when the particle position varied. Subsequently, the obtained data were partitioned into training, validation, and testing datasets at a 7:2:1 ratio. To convert the DEM model into a multi-dimensional matrix that computers can recognize, the 3D DEM models were first sliced to extract multi-layer two-dimensional (2D) cross-sectional data. Redundant information was then eliminated via gray processing, and the data were stacked to form a new 3D matrix representing the granular soil's fabric. Subsequently, utilizing the Python language and Pytorch framework, a 3D convolutional neural networks (CNNs) model was developed to establish the relationship between the constrained modulus obtained from DEM simulations and the soil's fabric. The mean squared error (MSE) function was utilized to assess the loss value during the training process. When the learning rate (LR) fell within the range of 10-5–10-1, and the batch sizes (BSs) were 4, 8, 16, 32, and 64, the loss value stabilized after 100 training epochs in the training and validation dataset. For BS = 32 and LR = 10-3, the loss reached a minimum. In the testing set, a comparative evaluation of the predicted constrained modulus from the 3D CNNs versus the simulated modulus obtained via DEM reveals a minimum mean absolute percentage error (MAPE) of 4.43% under the optimized condition, demonstrating the accuracy of this approach. Thus, by combining DEM and CNNs, the variation of soil's mechanical characteristics related to its random fabric would be efficiently evaluated by directly tracking the particle assemblages.

Prognostic significance of systemic immune-inflammation index in patients with nonfunction pancreatic neuroendocrine tumor undergoing surgical resection.

The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune-inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow-up of 98 months. Univariate analysis showed that higher SII (p < 0.0001), tumor size >4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease-free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p < 0.0001) and G2/G3 grade (HR: 3.11; 95% CI: 1.42, 6.82; p = 0.005) remained significantly associated with tumor recurrence. Furthermore, 46 (12.6%) patients died during the follow-up. Higher SII (HR: 8.43; 95% CI: 3.19, 22.72; p < 0.0001) and G2/G3 grade (HR: 3.16; 95% CI: 1.01, 9.86; p = 0.048) were independent predictors of overall survival (OS) by multivariate analysis. In conclusion, our study revealed that a higher SII level was associated with tumor-related features (larger tumor size and advanced grade) and subsequent shorter DFS and OS in patients with nonfunctioning pNETs. These results indicated that the SII could serve as an efficient prognostic biomarker for nonfunctioning pNETs.

Energy absorption and mechanical response of Graded face-centered cubic structures

Enhancing the energy absorption capability of lightweight structures, through the use of functionally-graded materials, has recently attracted attention. The thickness grading method of plate lattices in the literature is limited to a discrete layer-by-layer grading, as the thickness in any single layer is uniform but different from the thickness of the other layers. The sudden changes between the layers result in a stress concentration. A continuous thickness grading is achieved in this study, and the effect of employing distinct grading schemes applied to FCC structures has been investigated. Axial continuous thickness grading, lateral continuous thickness grading, and an axial-lateral hybrid continuous thickness grading are examined, alongside discrete layer-by-layer unit cell size grading. Manufactured from Nylon using the material extrusion additive manufacturing method, the samples were benchmarked against uniform structures. To further understand the behavior of these structures, a numerical study, via Abaqus models of the quasi-static compression test, was undertaken and the resulting predictions offered good agreement with the experimental data. The axial thickness grading exhibits significant potential, resulting in a substantial increase of up to 39 % in specific energy absorption due to the layer-by-layer deformation, compared to their uniform counterparts. In contrast, unit cell size grading compromises the energy absorption efficiency, while improving the crushing force efficiency by 35 %. A higher mean crushing force up to 8 % was achieved by the lateral grading method. This investigation highlights the effect of adopting distinct grading approaches on both energy absorption and mechanical response, yielding useful information for the design of advanced protective systems.

The distribution of hrHPV genotypes among cervical cancer cases diagnosed across Ghana: a cross-sectional study

BackgroundThe burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs.MethodsA descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05.ResultsA total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV.ConclusionWe affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.

Prognostic Factors Associated with Tumor Recurrence and Overall Survival in Soft Tissue Sarcomas of the Extremities in a Colombian Reference Cancer Center.

Introduction: Soft tissue sarcomas (STS) are low-incidence tumors whose clinical and histopathological factors are associated with adverse oncological outcomes. This study evaluated prognostic factors (PF) associated with tumor recurrence and overall survival (OS) in patients diagnosed with STS of the extremities, treated at the Instituto Nacional de Cancerología (INC), Bogotá, Colombia. Materials and Methods: An analytical observational study of a historical cohort was carried out, including patients diagnosed with STS and managed surgically in the Functional Unit for Breast and Soft Tissue Tumors of the INC from January 2008 to December 2018. Results: A total of 227 patients were included; 74.5% had tumors greater than 5 cm. Most patients (29.1%) were in stage IIIB at diagnosis. Age was associated with higher mortality (HR = 1.01; CI95%: 1-1.02; p = 0.048). Tumor persistence at admission to the INC (HR = 2.34; CI95%: 1.25-4.35; p = 0.007) and histologic grade III (HR = 5.36; CI95%: 2.29-12.56; p = <0.001) showed statistical significance in the multivariate analysis for recurrence of any type, as did the PFs associated with a higher risk of local recurrence (HR = 2.85; CI95%: 1.23-6.57; p = 0.014 and HR = 6.09; CI95%: 2.03-18.2; p = 0.001), respectively. Tumor size (HR = 1.03; CI95%: 1-1.06; p = 0.015) and histologic grade III (HR = 4.53; CI95%: 1.42-14.49; p = 0.011) were associated with a higher risk of distant recurrence. Conclusions: This cohort showed that in addition to histologic grade and tumor size, tumor persistence at the time of admission has an impact on disease recurrence, so STS should be managed by a multidisciplinary team with experience in this pathology in high-volume reference centers.

Analysis of Pore Structure of Rice Husk Ash Concrete Under Freeze-Thaw Cycling

A microscopic experimental study was conducted on the rice husk ash cement paste under freeze-thaw cycles using mercury intrusion porosimetry. The study mainly focused on the influence of rice husk ash on the pore structure of the cement paste through analyses of porosity, pore size distribution, most probable pore size, pore size gradation, and critical pore size under freeze-thaw cycles. The results showed that with an increase in the rice husk ash content under the same freeze-thaw cycles, the porosity of the cement paste decreased, and both the pore size distribution and the most probable pore size decreased. This indicates that the addition of rice husk ash improves the pore structure of the concrete and enhances its frost resistance. Furthermore, as the rice husk ash content increased, the number of harmful and deleterious pores in the cement paste decreased, and the critical pore size decreased, demonstrating the improved durability performance of the concrete with the addition of rice husk ash.

Abstract 1622: Characterization of the phylogenetic relationships in bilateral breast angiosarcoma

Abstract Background: Breast angiosarcoma represents around 20% of all angiosarcomas, and often spread to lung, liver, and bones. Driver mutations of angiosarcoma, specifically PTPRB, and PLCG1, are well-known as reported previously. Notably, contralateral breast is another metastatic site of the breast angiosarcoma, where an unusual location for other soft tissue sarcomas. However, it remains uncertain whether the contralateral disease originates from the primary tumor or emerges independently. Here, we present a 75-year-old woman with bilateral breast angiosarcomas to investigate the genetic relationship between the tumors. Methods: Irregular and heterogeneous masses were synchronously detected through breast sonography. Whole genome sequencing (WGS) was conducted at 60X coverage using bilateral total mastectomies, along with a matched normal blood sample (n=1). Single nucleotide variants (SNVs) and small indels were identified using Strelka2 and Varscan2. Subsequent filtering was performed using custom Python scripts to establish high-confidence variants. A phylogenetic tree was then reconstructed based on SNVs to trace clonal evolution and distinguish between de novo primary and metastasis. Following this, COSMIC mutational signatures were analyzed to characterize the genomic profile. Results: For the left breast angiosarcoma, we found 1,086 SNVs and 101 indels, while the right breast angiosarcoma had 921 SNVs and 92 indels. Despite their small size (&amp;lt;1.0 cm) and low FNCLCC grade (G1), these two cancers shared 600 SNVs and 135 indels as “truncal events”, indicating that one side metastasized from the other. According to the phylogenetic tree and the molecular clock of the two angiosarcomas, we estimated that the metastasis occurred during the middle stages of cancer evolution. Additionally, we identified 7 nonsynonymous SNVs (ADAMTS7, RPS15, CYP2A6, OR1S2, ARHGAP23, GNAQ, UGT2B7), five of which were shared. Remarkably, the GNAQ driver mutation exhibited a mutation at codon 209, a hotspot mutation not previously reported in breast angiosarcoma. The dominant Cosmic mutational signatures were SBS1/5 and ID1/2, all of which were associated with aging. Conclusion: Our findings demonstrate that bilateral breast angiosarcomas metastasized from one side to the other, as evidenced by the WGS data. This study underscores that the capability of WGS to distinguish between oligometastatic disease and multiple primary cancers, which has implications for predicting patients’ prognosis. Citation Format: Minju Kim, Jeonghwan Youk, Soyeon Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Myung Geun Song, Jiwon Koh, Jeong Mo Bae, Hyeong-Gon Moon, Seock-Ah Im. Characterization of the phylogenetic relationships in bilateral breast angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1622.

Abstract 1138: A single-cell spatially resolved atlas of immune-mediated control of lung adenocarcinoma using 1,000-plex single-cell spatial molecular imaging in a transgenic mouse model

Abstract Background: Lung adenocarcinoma is one of the leading causes of cancer-related mortality. One of the most frequently occurring mutations in lung cancer is KRAS mutations. Recent development of chemical inhibitors that specifically target oncogenic variants of Ras, particularly the commonly mutated KRAS-G12D isoform, represents a significant breakthrough in targeted therapeutics. The tissue-level mechanisms underlying the cell-autonomous and non-cell-autonomous effects of KRas-G12D inhibitors are poorly understood. Additionally, the effectiveness of KRas-G12D inhibitors in lung cancer models remains unknown. To address these gaps in knowledge, we analyzed the spatial interactions between cancer cells and the surrounding tissue microenvironment during the process of tumor eradication mediated through KRas-G12D inhibitors. Methods: We utilized a genetic mouse model of non-small cell lung cancer (NSCLC), driven by the activation of KRas-G12D in combination with the loss of p53. We investigated the immune-mediated tumor recognition following the targeting of KRas-G12D in an immunocompetent setting. Lung samples were collected from control mice and treated. Spatial transcriptomic analysis (CosMxTM SMI 1,000-plex Mouse Universal Cell Characterization Panel) were employed to obtain a high-plex, single-cell, temporal and spatially resolved molecular atlas of lung tumor regression. Results: Prior to Kras inhibitor treatment, mice displayed both LuAD and lung adenomas. Lesion size and histological grade progressively decrease during pharmacological treatment with Kras inhibitor. 906 unique genes were detected above background on intact FFPE tissue slides, along with 4 protein markers for optimal single-cell segmentation results. Concordance between CosMx SMI and scRNAseq was assessed and demonstrated high assay sensitivity and specificity of the CosMx assay. LUAD cell subtypes were identified and showed distinct spatial features. Molecular states, and receptor-ligand interactions, within niche-specific signaling networks were investigated to underline molecular mechanism of immune attack and eventual eradication of tumors. Conclusion: This study provides novel insights into the temporal and spatial dynamics of KRas-G12D inhibitor-mediated tumor regression in lung cancer, shedding light on the previously unknown cell-cell interactions occurring during this process. By investigating these spatiotemporal aspects, we aim to enhance our understanding of lung cancer biology and potentially identify new immunotherapeutic biomarkers. Moreover, the research tools used in this study have implications for the design of future preclinical studies exploring the potential of immuno-oncology combination therapies. FOR RESEARCH USE ONLY. Not for use in diagnostic procedures. Citation Format: Tito Panciera, Francesca Zanconato, Michelangelo Cordenonsi, Mattia Forcato, Giada Vanni, Silvio Bicciato, Julian Preciado, Saskia Ilcisin, Katrina V. Raay, Margaret Hoang, Michael Patrick, Shanshan He, Joseph Beechem, Stefano Piccolo. A single-cell spatially resolved atlas of immune-mediated control of lung adenocarcinoma using 1,000-plex single-cell spatial molecular imaging in a transgenic mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1138.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer

ImportanceThe identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in breast cancer patients. The current study aims to investigate if tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. MethodsWe included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases (AXN+) as well as 230 patients without lymph node metastasis. Based on pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DE-MRI), we assessed contact of the tumor to the internal mammary perforating vessels (IMPV). Results59 patients had ipsilateral IMN+ (iIMN+), 10 patients contralateral IMN+ (cIMN+) and 228 patients had ipsilateral axillary metastases without IMN. 230 patients had node negative breast cancer. In patients with ipsilateral IMN+, 100% of tumors had contact with ipsilateral IMPV with 94.9% (n=56) classified as major contact. In iIMN- patients on the other hand, major IMPV contact was observed in only 25.3% (n=116) and 36.2% (n=166) had no IMPV contact at all. Receiver operating characteristic (ROC) analysis revealed that “major IMPV contact” was more accurate in predicting ipsilateral IMN+ (AUC 0.85) compared to a multivariate model combining grade of differentiation, tumor site, size and molecular subtype (AUC 0.65). Strikingly, among patients with contralateral IMN+ (cIMN+), 100% of tumors had contact to a crossing contralateral IMPV, whereas in contralateral IMN- (cIMN-) patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. ConclusionTumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of breast cancer patients for IMNI.

X-ray tomography applied to tsunami deposits: Optimized image processing and quantitative analysis of particle size, particle shape, and sedimentary fabric in 3D

The analysis of particle size, shape, size, and their spatial arrangement (i.e. fabric) in a sedimentary deposit plays a significant role in their interpretation in terms of transport mechanism, flow conditions, and sediment source. The present work focuses on the use of X-ray computed tomography (X-CT) to analyze tsunami deposits (core samples), as examples of complex sedimentary assemblages. A workflow of image processing is proposed to measure 3D parameters of particle size, shape, and orientation using two different software packages (Fiji-ImageJ, and IPSDK) and two different methods of image segmentation. The semi-automated method provides better segmentation quality of the tsunami deposit, as compared with the poor performance of fully-automated image segmentation. We also provide some clues to reduce the computational time. This workflow is applied to two examples of tsunami deposits on the coasts of the Algarve (1755 Lisbon tsunami, southern Portugal). Optimized processing of X-CT images gives access to detailed vertical variations of grain size, grain shape, and componentry (clayey matrix, silicates, and carbonates, including marine bioclasts), as well as information on flow directions inferred from the sedimentary fabric in 3D. High-resolution analysis of the bedforms and vertical grain size grading allows determining the flow conditions during the inundation phase of the tsunami.

Risk factors and prognosis of sentinel lymph node metastasis in breast-conserving breast cancer: A retrospective study based on the SEER database.

At present, the risk factors and prognosis of sentinel lymph node metastasis (SLNM) are analyzed based on the study of axillary lymph node metastasis, but whether there is a difference between the two is unclear. Therefore, an accurate and appropriate predictive model needs to be proposed to evaluate patients undergoing sentinel lymph node biopsy (SLNB) for breast cancer. We selected 16983 women with breast cancer from the Surveillance Epidemiology and End Results (SEER) database. They were randomly assigned to two cohorts, one for development (n = 11891) and one for validation (n = 5092). multi-factor logistics regression was used to distinguish risk factors affecting SLNM. The potential prognostic factors were identified using the COX regression analysis. The hazard ratio (HR) and 95% confidence interval (95%CI) were calculated for all results. Multiple Cox models are included in the nomogram, with a critical P value of .05. In order to evaluate the model's performance, Concordance index and receiver operating characteristic curves were used. Six independent risk factors affecting SLNM were screened out from the Logistic regression, including tumor location, number of regional lymph nodes (2-5), ER positive, PR positive, tumor size (T2-3), and histological grade (Grade II-III) are independent risk factors for SLNM in patients (P < .05). Eight prognostic factors were screened out in the multivariate COX regression analysis (P < .05): Age: Age 60 to 79 years, Age ≥ 80 years; Race; Histological grading: Grade II, Grade III; No radiotherapy; Tumor size: T2, T3; ER positive:, sentinel lymph node positive, married. Histological grade, tumor location, T stage, ER status, PR status and the number of SLNB are significantly correlated with axillary SLNM. Age, ethnicity, histological grade, radiotherapy, tumor size, ER status, SLN status, and marital status were independent risk factors for Breast cancer specific survival (BCSS). Moreover, the survival rate of patients with 3 positive SLNs was not significantly different from that with one or two positive SLNs, We concluded that patients with stage N1 breast cancer were exempt from axillary lymph node dissection, which is worthy of further study.

Experimental Study on Workability of Natural Aggregate Concrete Incorporated with Crumb Rubber

This study investigated the effect of crumb rubber on the workability of fresh concrete. Crumb rubber was used to replace fine aggregate at 0%, 5%, 10%, 15% and 25%. Physical properties (particle size gradation, specific gravity, bulk density and aggregate impact value) of the aggregates: sharp sand, Bida natural stone and crumb rubber were determined. Furthermore, the sharp sand and Bida natural stone used for this research were characterized as normal weight aggregates while the crumb rubber was characterized as a light weight aggregate. Workability of the concrete in its fresh state was extensively studied. Generally, the workability of fresh concrete reduced as the crumb rubber increased from 0% to 25%. The reduction in slump values was adduced to the absorbent nature of the crumb rubber. Hence, the research recommended a water-to-cement ratio of 0.55 – 0.60 for use in the production of concrete containing crumb rubber. It was concluded that crumb rubber can be used to produce low workability concrete for use in mass concrete foundations, lightly reinforced concrete elements and roads.

Experimental study on the effects of sediment size gradation and suspended sediment concentration on the settling velocity, ws

The settling velocity of non-uniform sediment is of great importance for the sediment transport on coasts and estuaries. Although existing settling velocity formulas have already considered factors such as the Suspended Sediment Concentration (SSC), temperature, salinity, turbulence, and the effect of size gradation on the settling velocity, more studies are needed. In this study, the fiber optic sensors and Particle Track Velocimetry (PTV) for high SSC were used to measure the settling velocity of two size gradations with different SSCs in a settling column in laboratory. The size gradation curves and settling velocities of these two non-cohesive sediment with SSCs ranged from 0.1 kg/m3 to 50 kg/m3 were obtained. When the SSC is less than or equal to 0.1 kg/m3, the settling velocity is close to the grain size distribution weighted average settling velocity. With the increase of SSC, the distance between sediment particles decreases, and the mutual influence between different components become important, resulting in a decrease in the settling velocity of large-sized particles and an increase in the settling velocity of small-sized particles. This phenomenon is more pronounced for natural sediments. Based on the experimental results, a particle size distribution correction coefficient was proposed to fit the fine-grained settling velocity in quiescent water considering size gradation and sediment concentration.