bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting convective blueshift and radial-velocity dispersion due to granulation for FGK stars
Authors: Dalal S , Haywood R D , Mortier A , Chaplin W J , Meunier N 
Published: August 2023

ABSTRACT
To detect Earth-mass planets using the Doppler method, a major obstacle is to differentiate the planetary signal from intrinsic stellar variability (e.g. pulsations, granulation, spots, and plages). Convective blueshift, which results from small-scale convection at the surface of Sun-like stars, is relevant for Earth-twin detections as it exhibits Doppler noise of the order of 1 $\rm m\, s^{-1}$. Here, we present a simple model for convective blueshift based on fundamental equations of stellar structure. Our model successfully matches observations of convective blueshift for FGK stars. Based on our model, we also compute the intrinsic noise floor for stellar granulation in the radial-velocity observations. We find that for a given mass range, stars with higher metallicities display lower radial-velocity dispersion due to granulation, in agreement with magnetohydrodynamic simulations. We also provide a set of formulae to predict the amplitude of radial-velocity dispersion due to granulation as a function of stellar parameters. Our work is vital in identifying the most amenable stellar targets for Extreme Precision Radial Velocity surveys and radial velocity follow-up programmes for TESS, CHEOPS, and the upcoming PLATO mission.
Centromere Plasticity With Evolutionary Conservation and Divergence Uncovered by Wheat 10+ Genomes
Authors: Ma Huan , Ding Wentao , Chen Yiqian , Zhou Jingwei , Chen Wei , Lan Caixia , Mao Hailiang , Li Qiang , Yan Wenhao , Su Handong 
Published: August 2023

Abstract
Centromeres (CEN) are the chromosomal regions that play a crucial role in maintaining genomic stability. The underlying highly repetitive DNA sequences can evolve quickly in most eukaryotes, and promote karyotype evolution. Despite their variability, it is not fully understood how these widely variable sequences ensure the homeostasis of centromere function. In this study, we investigated the genetics and epigenetics of CEN in a population of wheat lines from global breeding programs. We captured a high degree of sequences, positioning, and epigenetic variations in the large and complex wheat CEN. We found that most CENH3-associated repeats are Cereba element of retrotransposons and exhibit phylogenetic homogenization across different wheat lines, but the less-associated repeat sequences diverge on their own way in each wheat line, implying specific mechanisms for selecting certain repeat types as functional core CEN. Furthermore, we observed that CENH3 nucleosome structures display looser wrapping of DNA termini on complex centromeric repeats, including the repositioned CEN. We also found that strict CENH3 nucleosome positioning and intrinsic DNA features play a role in determining centromere identity among different lines. Specific non-B form DNAs were substantially associated with CENH3 nucleosomes for the repositioned centromeres. These findings suggest that multiple mechanisms were involved in the adaptation of CENH3 nucleosomes that can stabilize CEN. Ultimately, we proposed a remarkable epigenetic plasticity of centromere chromatin within the diverse genomic context, and the high robustness is crucial for maintaining centromere function and genome stability in wheat 10+ lines as a result of past breeding selections.
Angioleiomyoma mimicking a swollen bursa on first metatarsophalangeal joint accompanying with hallux valgus deformity
Authors: Matsuda Kotaro , Hirao Makoto , Noguchi Takaaki , Okamura Gensuke , Hoshida Yoshihiko , Etani Yuki , Ebina Kosuke , Okada Seiji , Hiraoka Koji , Hashimoto Jun 
Published: August 2023

ABSTRACT
We present a case of a patient who underwent a modified scarf osteotomy and tumour excision based on a preoperative diagnosis of hallux valgus deformity and accompanying bursitis. Subsequent histopathological examination revealed that the tumour was an angioleiomyoma. While tumours around the first metatarsophalangeal (MTP) joint are typically associated with gouty nodules, infections, or swollen bursa (bursitis) in patients with hallux valgus deformity, the occurrence of soft tissue tumours in this area is rare. Moreover, angioleiomyoma is an even rarer form of soft tissue tumour and is seldom suspected prior to resection. To our knowledge, there have been no reports of angioleiomyoma arising in the first MTP joint. However, it is important to consider the possibility of an atypical tumour in cases where soft tissue masses are present, even in patients with hallux valgus deformity, and to perform at least imaging tests such as ultrasound and magnetic resonance imaging before surgery. This prospect should always be kept in mind.
BSBM-06 UNRAVELING THE IMMUNE MICROENVIRONMENT OF BRAIN METASTASIS FROM LUNG ADENOCARCINOMA
Authors: Souza Vanessa G P , de Araújo Rachel P , Santesso Mariana R , Seneda Ana Laura , Minutentag Iael W , Hamamoto Filho Pedro T , Marchi Fábio A , Drigo Sandra A , Lam Wan L , Reis Patricia P 
Published: August 2023

Abstract
Brain metastasis (BM) is a common complication of advanced lung adenocarcinoma (LUAD) and is associated with significantly poor prognosis and reduced quality of life. The immune system plays a critical role in the development and progression of BM, as well as in response to therapy. Herein, we used Next-Generation Sequencing (NGS) and array technologies to elucidate the immune landscape of LUAD-BM. NGS data from BM and primary tumors (T): RNA-Seq (n=24; 13 BM and 11 T), microarray (n=140; 63 BM and 77 T) were used for quantifying the immune cell fractions by CIBERSORT. Additionally, single-cell (scRNA-seq) data (n=57,774 cells; 23 BM samples) were used for data validation. Results showed that resting memory T CD4 comprised the largest cellular fraction (17.4%) of the total immune cells in BM. Furthermore, the fraction of resting dendritic cells (DC) was lower in BM vs. T, while the neutrophil fraction was higher (p&lt;0.05). ScRNA-seq confirmed the presence of DC and neutrophils in BM, identifying multiple subsets of DC (cDC1, cDC2/MoDC, and DC3) that are highly conserved across solid human cancers with cDC2/MoDC as the most frequent subpopulation among dendritic cells. Therefore, our results show a different immune profile between BM and primary LUAD. The immune environment of LUAD-BM is highly suppressed, accompanied by enriched T cell subpopulations predicted as immature T cells. The identification of cDC2/MoDC subpopulations in LUAD-BM replicates the findings observed in BM from melanoma patients. It has been shown that cDC2 can interact with CD4+ T cells to promote anti-tumor immune responses. Our findings elucidate the profiles of LUAD-BM immune microenvironment, comprehensively identifying specific immune subpopulations with important roles in the establishment and progression of BM from LUAD.
BSBM-12 STAT3 EXPRESSION IN BRAIN METASTASES FROM BREAST CANCER: CORRELATIONS WITH DIFFERENT MOLECULAR SUBTYPES AND CLINICAL OUTCOME
Authors: Pellerino Alessia , Bruno Francesco , Bertero Luca , Bellini Elisa , Beano Alessandra , Montemurro Filippo , Valiente Manuel , Rudà Roberta , Soffietti Riccardo 
Published: August 2023

Abstract

BACKGROUND
STAT3 expression in peritumoral reactive astrocytes (RA) of brain metastases (BM) from breast cancer (BC) may favor a pro-metastatic environment.

MATERIAL AND METHODS
105 BM specimens from BC were identified from the biobank of Pathology Unit of University of Turin and Spanish national BrM network (RENACER). pSTAT3 expression was scored in RA of peritumoral tissue according to Priego et al. (Nat Med 2018). Clinical, molecular data, and intracranial progression (i-PFS) were retrospectively retrieved.

RESULTS
Median age was of 50 years (range 46–54). 31/105 patients (29.5%) had luminal BM, 35/105 (33.3%) had HER2-positive BM, and 39/105 (37.1%) had triple negative BM. Immunohistochemistry for GFAP and pSTAT3 was feasible in 88/105 (83.8%). 49/88 (55.7%) showed positive staining of pSTAT3, of which 15/88 (17%) scored with 3, 34/88 (38.6%) with 2, 28/88 (31.9%%) with 1, and 11/88 (12.6%) with 0 (negative). High pSTAT3 expression (score 2-3) was observed in 27/34 (79.4%) triple negative BM, and in 18/30 (60.0%) HER2-positive BM, while most of luminal BM (20/24 – 83.3%) had low or absent pSTAT3 expression. Median i-PFS was 16.0 months (range 7-80): low pSTAT3 BM (score 0-1) had a median i-PFS of 11 months versus 8 months for high pSTAT3 BM (score 2-3) (HR 0.4; p=0.0123). A shorter median i-PFS was observed in high pSTAT3 triple negative BM (4 months) as compared with low pSTAT3 BM (20 months). Conversely, i-PFS of high pSTAT3 BM (7 months) was similar to low pSTAT3 BM (7 months) in HER2-positive BC.

CONCLUSION
pSTAT3 expression in RA of triple negative BM and HER-2 positive BM is higher than in luminal BM. Of note, patients with high pSTAT3 triple negative BM progressed earlier in comparison with those with low pSTAT3, suggesting that pSTAT3 expression has an influence on the outcome.
BSBM-13 MELANOMA CELLS PRODUCE A SUSPENSION SUB-POPULATION THAT DRASTICALLY DISRUPTS THE BLOOD-BRAIN BARRIER ENDOTHELIUM
Authors: Anchan Akshata , Spurling Dayna , Hucklesby James , Finlay Graeme , Angel Kate , Graham E Scott 
Published: August 2023

Abstract
Melanoma metastasizes to the brain with high propensity. Brain metastasis requires cancer cells to breach the blood-brain barrier (BBB) endothelium, which forms the first line of defence against blood-borne pathogens. An increasing number of molecules are discussed in BBB disruption, and their importance varies across melanoma and endothelial cell lines. This diversity in literature proposes that cancer cells of the same cancer type employ different modes of metastasis. This study shows an example of the difference in migration capabilities of adherent melanoma cells and a suspension sub-population. We used Electric Cell-substrate Impedance Sensing (ECIS) to assess changes in human brain endothelial barrier function upon adding human melanoma lines. Several melanoma lines induced brain endothelial barrier disruption within the first few hours of addition. Intriguingly, the suspension population of melanoma cells disrupted the endothelial barrier faster and more drastically than the adherent counterpart. Time-lapse imaging revealed that the suspension population used a transcellular route of invasion compared to the paracellular route used by the adherent cells. Confocal microscopy supported this, showing clear differences in the physical interaction of the suspension subtype with the brain endothelium, compared to the adherent cells. Flow cytometry and NanoString technology allowed characterization of the melanoma lines, showing that the suspension subtype protein composition differs from their adherent counterpart. We hypothesize that melanoma cells may produce specific subtypes that are more invasive, which can accelerate migration through the brain endothelium. We stress the importance of investigating the composition of melanoma cells and their bi-products when researching cancer metastasis. Once successfully within the brain parenchyma, these cancer cells are effectively separated from the peripheral adaptive immune system, designed to detect and eliminate them. Therefore, preventing cancer cell migration into the brain is an attractive consideration, as they are considerably more targetable whilst still in the blood.
BSBM-22 CHARACTERIZATION OF CIRCULATORY SHEAR STRESS-INDUCED MOLECULAR CHANGES IN LUNG ADENOCARCINOMA CELLS AND IMPLICATIONS IN BRAIN METASTASIS
Authors: Marenco-Hillembrand Lina , McKevitt Chase , Bamimore Michael , Wickland Daniel , Schiapparelli Paula , Maharjan Sushila , Zhang Yu Shrike , Quinones-Hinojosa Alfredo , Chaichana Kaisorn L 
Published: August 2023

Abstract

INTRODUCTION
Lung cancer is the most common tumor to metastasize to the brain, as 40% of patients develop brain metastasis (BM). Once diagnosed, survival is only 6.5-10 months. A potential target to prevent BM is circulating tumor cells (CTCs). The mechanisms that mediate a CTCs adaptation to the harsh environment of circulation and BM have not been elucidated. We have demonstrated that primary lung cancer cells (LCCs) subjected to circulation have increased migration across brain endothelial cell monolayers, increased side population, and decrease survival in rodents when injected intracardially vs plated controls.

METHODS
We engineered a microfluidic device capable of subjecting tumor cells to prolonged circulatory shear stress (CSS) that allows the isolation/modeling of CTC-like cells. Primary LCCs (A549, H1563) were subjected to circulation, suspension, or plated (2D) for 72h as controls. At this time point, LCCs were collected, and total mRNA was extracted. Samples were submitted for RNA sequencing. Weighted gene co-expression network analysis (WCGNA) and Ingenuity Pathway Analysis were performed. (FC &gt;2 and p-value &lt;0.05).

RESULTS
Transcriptomic analysis indicates that cells subjected to CSS activate specific gene networks involved in cell survival, migration, invasion, adhesion of tumor cells, and cytoskeletal reorganization (z-score: &gt;2, p-value: 0.05). Canonical pathways in CTCs included ILK-signaling and Xenobiotic Metabolism. LCCs exposed to CSS had increased expression of multidrug resistance pumps ABCC2, ABCF2 (P:&lt;0.001), and side population on flow cytometry (P: &lt;0.05). The top differentially expressed genes in CTC-like cells (MMP1, ANGPTL4, and CEMIP) were involved in the invasion, angiogenesis, and pre-metastatic niche (PMN) formation of BM.

CONCLUSION
LCCs that survive CSS have increased expression of genes associated with migration, invasion, and chemoresistance compared to 2D controls. Targeting genes in CTCs that mediate survival and preparation of the PMN may be useful in preventing BM.
LMAP-03 OUTCOME OF BRAIN METASTASES TREATED WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY (GKSR): COHORT RETROSPECTIVE STUDY ON 205 CASES
Authors: Bankole Nourou Dine Adeniran , Melhaoui Adyl , Arkha Yasser , Semmar Afaf , Bouyakhlef Khalid , Boutarbouch Mahjouba , Jiddane Mohamed , El Khamlichi Abdeslam 
Published: August 2023

Abstract

BACKGROUND
Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new brain metastases have more than one brain metastasis at the time of diagnosis.

OBJECTIVE
We report our experience of brain metastases treated with GKSR and evaluate the outcome.

METHODS
Patients treated by Gamma Knife stereotactic radiosurgery (GKSR) in our institution between 2008 and 2021 for BM were recorded retrospectively.

RESULTS
A total of 205 patients (56.6% females) were included, with a median age of 59 (25-83) years old. Breast (n=85, 42.5%) and lung (n=76, 38%) were the common original locations for the primary tumors (Table 1). There were 103 patients (50.3%) with single BM and 102 patients (49.7%) with multiple BM⩾2. The median number of multiple BM treated was 4 (2-43). The overall mean survival time was 6.00(95% CI, 5.07-6.93) months for all BM. The median percentage of tumor control after radiosurgery treatment was 65% (20-99) over the median follow-up time of 6.00(3-84) months. In the overall population, the 1-year OS rate was 37.55%, the 2-year OS rate was 25.12%, and the 5-year OS was 18.51%. The mean survival time among patients with BM was higher in those with multiple BM than those with single BM ([10 (95%CI 6.67-13.33) months vs 5(4.21-5.70) months, P (0.03)]). Retreatment, tumor stability (control), and progression influence the overall survival of BM, whether single or multiple (P&lt;0.001).

CONCLUSION
Stereotaxic Radiosurgery provides good results in terms of Overall survival and better Quality of Life for BM, whether single or multiple. Stability and retreatment influenced the overall survival of BM.
LMAP-04 CHOOSING WISELY BETWEEN RADIOTHERAPY DOSE-FRACTIONATION SCHEDULES: THE MOLECULAR GRADED PROGNOSTIC ASSESSMENT (MOLGPA) FOR ELDERLY GLIOBLASTOMA (EGBM-MOLGPA)
Authors: Lee Hye In , Kim Jina , Kim In Ah , Lee Joo Ho , Cho Jaeho , Yoon Hong In , Wee Chan Woo 
Published: August 2023

Abstract
This study aimed develop a prognostic model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT). Patients aged ≥65 years who underwent radiotherapy for IDH-wildtype eGBM between 2006 and 2021 were included. Patients planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT (334 patients; median, 60 Gy in 30 fractions) or HFRT (239 patients; median, 45 Gy in 15 fractions), respectively. We developed the molecular graded prognostic assessment score for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each prognostic factor for overall survival (OS). Temozolomide-based chemoradiation was applied for 86% of patients. With a median follow-up of 17.4 months, the median OS was 18.7 months for CFRT plus temozolomide group, 15.1 months for HFRT plus temozolomide group, and 10.4 months for RT alone group. The eGBM-molGPAwas established based on prognostic factors from multivariate analysis (performance, extent of resection, temozolomide, methylation of the MGMT promoter, subventricular zone involvement, temporalis muscle thickness, and the mutation status of TERT promoter and TP53 gene) and patients were allocated to three risk groups (high risk, total score 3.0–4.5; intermediate risk, 1.5–2.5; low risk, 0.0–1.0). Patients treated with CFRT plus temozolomide had significantly improved OS compared to those treated with HFRT plus temozolomide or radiotherapy alone in the low and intermediate risk groups (p&lt;0.001). However, in the high-risk group, there was no significant difference in OS between treatment options. CFRT plus temozolomide can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among radiotherapy options.
LMAP-09 RECAPITULATING LASER INTERSTITIAL THERMAL THERAPY IN PRECLINICAL BRAIN TUMOR MODELS
Authors: Haskell-Mendoza Aden , Wachsmuth Lucas , Fecci Peter 
Published: August 2023

Abstract
Laser interstitial thermal therapy (LITT) is a minimally-invasive option for cytoreduction of recurrent or otherwise difficult-to-access intracranial tumors. Relative to resection, ablated tumor tissue remains in situ, facilitating recognition of tumor antigens and a targetable immune response. To investigate the immune consequences of LITT, we developed a model of stereotactic laser ablation for use with existing syngeneic glioma and intracranial metastasis cell lines. A 1064 nm diode-based Nd:YAG laser (Monteris Medical) was used to thermally ablate normal brain tissue or CT-2A tumors in C57BL6/J mice. Ablations were performed at 10 days post-implantation at + 2 ML, + 1 AP, -3 DV using a stereotactic frame. Simultaneous temperature measurements were taken using a thermocouple probe implanted to the same depth 2 mm posterior. We first used serial T2-weighted MRI imaging to accurately track the tumor growth characteristics and identify a safe lesion size for ablation, selecting 10 days post-implantation for subsequent experiments and 2 mm posterior as the ideal position to monitor temperature at the lesion edge. To assess the thermal characteristics of our laser, we ablated mouse brains at 1 W and 2 W for 30, 60, or 90 seconds each, finding that 1 W for 90 seconds produced an ablation that did not char or coagulate tissue outside the ablation zone and recapitulated human ablation findings on H&E staining 24h post-LITT. We next implanted CT-2A tumors for ablation with the selected dose, following mice for survival between the LITT and sham-ablated groups. A subset of mice were imaged using T2-MRI at 1, 3, 7, and 14 days post-surgery. Our model recapitulates the essential clinicopathological findings of LITT and is well suited apply to a variety of intracranial tumor models and LITT-adjunctive therapies.
LMAP-11 CYSTIC BRAIN METASTASES OUTCOMES FOLLOWING GAMMA KNIFE RADIOTHERAPY
Authors: Amidon Ryan , Livingston Katie , Kleefisch Christopher , Straza Michael , Puckett Lindsay , Schultz Christopher , Mueller Wade , Connelly Jennifer , Noid George , Morris Kirk , Bovi Joseph 
Published: August 2023

Abstract

BACKGROUND
The response of cystic brain metastases (BMets) to radiotherapy is poorly understood, with conflicting results regarding local control (LC), overall survival (OS), and treatment-related toxicity. This study aims to examine the role of Gamma Knife (GK) in managing cystic BMets.

METHODS
Volumetric analysis was conducted to measure tumor and edema volume at the time of GK and follow-up MRI studies. We evaluated the association of 4 variables with survival using Cox regression analysis and used the Kaplan-Meier method to estimate median survival times (MST).

RESULTS
Between 2016 and 2021, 54 patients with 83 cystic BMets were treated with GK at our institution. Lung cancer was the most common pathology (51.9%), followed by breast (13.0%). The mean target volume was 2.7 cc (range, 0.1-39.0 cc) and the mean edema volume was 13.9 cc (range, 0-165.5 cc). The median prescription dose of single fraction and fractionated GK was 20 Gy (range, 14-27.5 Gy). With a median follow-up of 8.9 months, MST was 11.1 months, OS was 33.3%, and the one-year LC rate was 75.9%. GK was associated with decreased tumor and edema volumes over time, although 68.5% of patients required steroids post-GK. Patients whose tumors grew beyond baseline following GK received significantly more pre-GK whole-brain radiation therapy (WBRT) than those whose tumors declined following GK. Higher age at diagnosis of BMets and pre-GK systemic therapy were associated with worse survival, with an MST of 7.8 months in patients who received it compared to 23.3 months in those who did not.

CONCLUSIONS
Pre-GK WBRT may select for BMets with increased radioresistance. This study highlights the ability of GK to control cystic BMets with the cost of high post-treatment steroid use.