bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyramiding of transgenic immune receptors from primary and tertiary wheat gene pools improves powdery mildew resistance in the field
Authors: Koller Teresa , Camenzind Marcela , Jung , Esther , Brunner Susanne , Herren Gerhard , Armbruster Cygni , Keller Beat 
Published: December 2023

Abstract
Introgression of resistance genes from wild or related species is a common strategy to improve disease resistance of wheat cultivars. Pm17 is a gene that confers powdery mildew resistance in wheat. It encodes an NLR type of immune receptor and was introgressed from rye to wheat as part of the 1RS chromosome arm translocation several decades ago. So far it has not been possible to separate Pm17 from its co-introgressed rye genes due to suppressed recombination. Here we tested in the field transgenic Bobwhite wheat overexpressing Pm17 without any other rye genes. Four transgenic events showed high levels of PM17 protein accumulation, strong powdery mildew resistance, and no pleiotropic effects during three field seasons. We used a combined approach of transgene insertion and cross-breeding to generate lines co-expressing Pm17 and Pm3, or Pm17 and Pm8. Blumeria graminis f. sp. tritici infection tests confirmed additive, race-specific resistance of the two pyramided transgenes in lines Pm17+Pm3b and Pm17+Pm8. Furthermore, pyramided lines showed strong powdery mildew resistance during three field seasons. We conclude that the combination of overexpressed NLR genes from the extended gene pool broadens and diversifies wheat disease resistance.
Deep Learning Approach for High-accuracy Electron Counting of Monolithic Active Pixel Sensor-type Direct Electron Detectors at Increased Electron Dose
Authors: Wei Jingrui , Moore Kalani , Bammes Benjamin , Levin Barnaby D A , Hagopian Nicholas , Jacobs Ryan , Morgan Dane , Voyles Paul M 
Published: December 2023

Abstract
Electron counting can be performed algorithmically for monolithic active pixel sensor direct electron detectors to eliminate readout noise and Landau noise arising from the variability in the amount of deposited energy for each electron. Errors in existing counting algorithms include mistakenly counting a multielectron strike as a single electron event, and inaccurately locating the incident position of the electron due to lateral spread of deposited energy and dark noise. Here, we report a supervised deep learning (DL) approach based on Faster region-based convolutional neural network (R-CNN) to recognize single electron events at varying electron doses and voltages. The DL approach shows high accuracy according to the near-ideal modulation transfer function (MTF) and detector quantum efficiency for sparse images. It predicts, on average, 0.47 pixel deviation from the incident positions for 200 kV electrons versus 0.59 pixel using the conventional counting method. The DL approach also shows better robustness against coincidence loss as the electron dose increases, maintaining the MTF at half Nyquist frequency above 0.83 as the electron density increases to 0.06 e−/pixel. Thus, the DL model extends the advantages of counting analysis to higher dose rates than conventional methods.
The Magellanic Puzzle: origin of the periphery
Authors: Massana Pol , Nidever David L , Olsen Knut 
Published: December 2023

ABSTRACT
In this paper, we analyse the metallicity structure of the Magellanic Clouds using parameters derived from the Gaia Data Release 3 (DR3) low-resolution XP (for Blue/Red Photometer) spectra, astrometry, and photometry. We find that the qualitative behaviour of the radial metallicity gradients in the Large Magellanic Cloud (LMC) and Small Magellanic Cloud (SMC) is quite similar, with both of them having a metallicity plateau at intermediate radii and a second at larger radii. The LMC has a first metallicity plateau at [M/H] ≈ −0.8 for 3–7°, while the SMC has one at [M/H] ≈ −1.1 for 3–5°. The outer LMC periphery has a fairly constant metallicity of [M/H] ≈ −1.0 (10–18°), while the outer SMC periphery has a value of [M/H] ≈ −1.3 (6–10°). The sharp drop in metallicity in the LMC at ∼8° and the marked difference in age distributions in these two regions suggest that there were two important evolutionary phases in the LMC. In addition, we find that the Magellanic periphery substructures, likely Magellanic debris, are mostly dominated by LMC material stripped off in old interactions with the SMC. This presents a new picture in contrast with the popular belief that the debris around the clouds had been mostly stripped off from the SMC due to having a lower mass. We perform a detailed analysis for each known substructure and identify its potential origin based on metallicities and motions with respect to each galaxy.
Photometric determination of main-sequence binaries with Gaia
Authors: Wallace A L 
Published: December 2023

ABSTRACT
Since its launch in 2013, the Gaia space telescope has provided precise measurements of the positions and magnitudes of over 1 billion stars. This has enabled extensive searches for stellar and substellar companions through astrometric and radial velocity measurements. However, these surveys require a prior knowledge of any unresolved companion affecting the results which can be identified using photometry. In this work, Gaia’s magnitude measurements are combined with near-infrared observations from the Two Micron All Sky Survey (2MASS) and Wide-field Infrared Survey Explorer (WISE) catalogues and simulation-based inference is applied to constrain astrophysical parameters and search for hidden companions. This method is first tested on simulated sets of binary stars before expanding to Gaia’s non-single star catalogue. Using this test, a region is identified on the H–R diagram in which the method is the most accurate and all Gaia sources within that region are analysed. This analysis reproduces a known anticorrelation between metallicity and binary fraction. Finally, the method is applied to the nearby star cluster M67 and, using previous studies of the metallicity distribution, it is possible to improve constraints on binary fraction. From this the binary fraction in the cluster is calculated to vary from 30 per cent in the outer cluster to 45 per cent near the core. This is found to be significantly higher the 23 per cent binary fraction calculated for the wider stellar neighbourhood.
Population synthesis and parameter estimation of neutron stars with continuous gravitational waves and third-generation detectors
Authors: Hua Yuhan , Wette Karl , Scott Susan M , Pitkin Matthew D 
Published: December 2023

ABSTRACT
Precise measurement of stellar properties through the observation of continuous gravitational waves from spinning non-axisymmetric neutron stars can shed light onto new physics beyond terrestrial laboratories. Although hitherto undetected, prospects for detecting continuous gravitational waves improve with longer observation periods and more sensitive gravitational wave detectors. We study the capability of the Advanced Laser Interferometer Gravitational-Wave Observatory, and the Einstein Telescope to measure the physical properties of neutron stars through continuous gravitational wave observations. We simulate a population of Galactic neutron stars, assume continuous gravitational waves from the stars have been detected, and perform parameter estimation of the detected signals. Using the estimated parameters, we infer the stars’ moments of inertia, ellipticities, and the components of the magnetic dipole moment perpendicular to the rotation axis. The estimation of the braking index proved challenging and is responsible for the majority of the uncertainties in the inferred parameters. Using the Einstein Telescope with an observation period of $5\, {\rm {yr}}$, point estimates using median can be made on the moments of inertia with error of $\sim 10\!-\!100~{{\ \rm per\ cent}}$ and on the ellipticities with error of $\sim 5\!-\!50~{{\ \rm per\ cent}}$, subject to the inference of the braking index. The perpendicular magnetic dipole moment could not be accurately inferred for neutron stars that emit mainly gravitational waves.
New constraints on the molecular gas content of a z ∼ 8 galaxy from JVLA CO(J = 2–1) observations
Authors: Jones Gareth C , Witstok Joris , Concas Alice , Laporte Nicolas 
Published: December 2023

ABSTRACT
As the primary fuel for star formation, molecular gas plays a key role in galaxy evolution. A number of techniques have been used for deriving the mass of molecular reservoirs in the early Universe (e.g. [C ii]158 µm, [C i], dust continuum), but the standard approach of CO-based estimates has been limited to a small number of galaxies due to the intrinsic faintness of the line. We present Jansky Very Large Array observations of the $z\sim \, 8.31$ galaxy MACS0416_Y1, targeting CO(2-1) and rest-frame radio continuum emission, which result in upper limits on both quantities. Adding our continuum limit to the published far-infrared (FIR) spectral energy distribution, we find a small non-thermal contribution to the FIR emission, a low-dust mass (${\rm {\log }}_{10}({\rm {\mathit{ M}}}_{\rm {D}}/{\rm M}_{\odot })\sim 5$), and an abnormally high-dust temperature (${\rm \mathit{ T}}_{\rm D}\gtrsim \, 90\, \mathrm{ K}$) that may indicate a recent starburst. Assuming a low metallicity (Z/Z⊙ ∼ 0.25), we find evidence for $M_{{\rm {H}}_2}, \mathrm{ CO}\lesssim \, 10^{10}$ M⊙, in agreement with previous [C ii] investigations ($M_{{\rm {H}}_2},[\mathrm{ C}\,\small{\rm II}]\, \sim \, 10^{9.6}$ M⊙). Upcoming JWST observations of this source will result in a precise determination of Z, enabling better constraints and an unprecedented view of the gaseous reservoir in this primordial starburst galaxy.
Are patients with primary glomerular disease at increased risk of malignancy?
Authors: Han Jialin , Zhao Yinshan , Canney Mark , Atiquzzaman Mohammad , Keown Paul , Levin Adeera , Barbour Sean 
Published: December 2023

ABSTRACT
Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases and the development of malignancies, with an estimated risk ranging from 5 to 11%. These malignancies include solid organ tumours as well as haematologic malignancies such as lymphoma and leukaemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of glomerular disease cases that were potentially secondary to an underlying malignancy, misclassification of glomerular disease type and ascertainment bias arising from an increased likelihood of physician encounters compared with the general population. Consequently, population-based studies that accurately evaluate the cancer risk in glomerular disease populations are lacking. While it is speculated that long-term use of immunosuppressive medications and glomerular disease activity measured by proteinuria and estimated glomerular filtration rate may be associated with cancer risk in patients with glomerular disease, the independent role of these risk factors remains largely unknown. The presence of these knowledge gaps could lead to a lack of awareness of cancer as a potential chronic complication of glomerular disease, underutilization of routine screening practices in clinical care that allow early diagnosis and treatment of malignancies and underrecognition of modifiable risk factors to decrease the risk of de novo malignancies over time. This review summarizes the current evidence on the risk of cancer in patients with glomerular diseases, explores the limitations of prior studies and discusses methodological challenges and potential solutions for obtaining accurate estimates of cancer risk and identifying modifiable risk factors unique to GN populations.
ED-1 PITUITARY TUMORS IN 5TH WHO CLASSIFICATION 2022: WHAT DO YOU MEAN BY PITNET?
Authors: Osamura Robert Y 
Published: December 2023

Abstract
It has been well known that the terminology has been changed from pituitary adenoma(4th WHO) which means benign epithelial tumors to pituitary neuroendocrine tumor(5th WHO 2022). It is apparent that the anterior pituitary cells and derived tumors contain intracytoplasmic neurosecretory granules and belong to neuroendocrine cells, and naturally neuroendocrine tumors. The pancreatic and gastrointestinal neuroendocrine neoplasms(NEN) are composed of well differentiated neuroendocrine tumors(NET) and poorly differentiated neuroendocrine carcinoma(NEC). NETs are potentially malignant(metastatic) tumors and are further graded to G1,G2,G3 by proliferative activities(mitoses or Ki-67 indices) showing correlation with prognosis . PitNET which means pituitary NET is now classified by transcription factors(PIT1,TPIT,SF1) and some tumors show clinical symptoms,(hormone production) invasive growth and rarely metastasize indicating potential malignant behavior. From this broad biological spectrum of PitNET, ICD-O coding /3(primary malignancy) has been proposed(5th WHO CNS, Pediatrics and Endocrine volumes). It has been known that some histological patterns (Sparsely granulated somatotroph PitNET, Crooke cell PitNET and others) are related more aggressive growth of PitNETs, but metastatic behavior is very hard to predict histologically. So in WHO 4th edition, the term pituitary carcinoma was used only after confirming metastasis or remote spread. The metastatic tumors are now called metastatic PitNETs. Five tiered grading by proliferation and invasion has been also proposed(Trouillas). Now we need more updated genomic studies such as single cell RNA sequencing to clarify biologic behavior of the individual PitNET cells to further clarify the their nature. . In my talk, several points of interests regarding PitNETs will be discussed by demonstrating histology and biology of representative cases.
10001-ACT-1 A MULTICENTER EXPLORATORY PHASE II STUDY OF NEOADJUVANT BEVACIZUMAB FOR NEWLY DIAGNOSED MALIGNANT GLIOMA - THE SECOND REPORT
Authors: Tanaka Toshihide , Tamura Ryota , Takei Jun , Morimoto Yukina , Teshigawara Akihiko , Tohmoto Kyoichi , Kuranari Yuki , Imai Ryotaro , Yamamoto Yohei , Hasegawa Yuzuru , Akasaki Yasuharu , Murayama Yuichi , Miyake Keisuke , Sasaki Hikaru 
Published: December 2023

Abstract

BACKGROUND
Preoperative bevacizumab (Bev) is a standard treatment strategy for colorectal cancers, but not malignant gliomas. This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bev for newly diagnosed glioblastoma (GB).

METHODS
Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The initial safety evaluation was performed for the initial 7 cases and efficacy was evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy.

RESULTS
The study protocol was judged as acceptable. Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case, according to the WHO 2016 criteria. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Tumor volume decrease rate on T1CE and PFS tended to correlate. Median PFS and overall survival were 9.5 months and 16.5 months, respectively.

CONCLUSIONS
Preoperative Bev and TMZ is confirmed to be safe. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively.
10007-ACT-2 FIRST IN HUMAN STUDY OF DSP-0390, AN ORAL EMOPAMIL BINDING PROTEIN (EBP) INHIBITOR, IN RECURRENT HIGH-GRADE GLIOMA (HGG): PRELIMINARY RESULTS
Authors: Arakawa Yoshiki , Goldlust Samuel A , Colman Howard , Reardon David A , Welch Mary R , Yamaguchi Shigeru , Butowski Nicholas A , Li Jian , Iino Shuichi , Song Gregory , Jackman Aimee , Xie Yuran , Wagle Marie-Claire , Lebedinsky Claudia , Narita Yoshitaka 
Published: December 2023

Abstract

BACKGROUND
Cholesterol in the brain is derived wholly from de novo biosynthesis as the blood-brain barrier prevents uptake from the circulation. The overexpression of cholesterol synthesis genes is associated with decreased survival in glioblastoma (GBM), suggesting that gliomas may be sensitive to the inhibition of cholesterol biosynthesis. DSP-0390 is an investigational small molecule that inhibits EBP, a key enzyme in cholesterol biosynthesis. Preclinical studies demonstrated antitumor activity of DSP-0390 in orthotopic xenograft GBM models.

METHODS
This phase I dose escalation study aims to assess the safety, PK, PD, and preliminary antitumor activity of oral DSP-0390 monotherapy for recurrent HGG (NCT05023551). Key eligibility criteria include histologically confirmed grade III or IV glioma (WHO 2016); treatment with ≥1 prior therapy; no treatment options beyond standard of care; KPS ≥70.

RESULTS
As of 9 May 2023, 24 patients (37.5% women) were enrolled across 6 dose levels (20 mg QD to 240 mg QD) with a median age of 51 years (range 24-76) including 17 (70.8 %) with GBM, 3 (12.5%) with anaplastic astrocytoma and 2 (8.3%) with anaplastic oligodendroglioma. Ten patients (41.7%) had IDH mutant tumors. Four patients (16.7%) were on stable dose of corticosteroids at baseline, of which 2 were able to discontinue or dose reduce the corticosteroid while on DSP-0390. There were no reported DLTs. The most common treatment-related TEAEs included grade 1 or 2 nausea (7 patients [29.2%]) and alanine aminotransferase increased (6 patients [25.0%]). Only one grade 3 related AE (dry skin) was noted. Two patients with IDH mutant grade 3 glioma had tumor reduction and remain on DSP-0390 for ≥9 months. Dose dependent changes in PK and PD were observed.

CONCLUSIONS
DSP-0390 has been well tolerated to date with dose escalation ongoing. A dose response relationship was observed between PK and PD biomarkers.
10021-IMT-1 A ROLE OF DENDRITIC CELL IMMUNOTHERAPY AS A MODALITY IN MULTIDISCIPLINARY THERAPY FOR GLIOBLASTOMA
Authors: Akasaki Yasuharu , Takei Jun , Yamamoto Yohei , Tanaka Toshihide , Teshigawara Akihiko , Kamata Yuko , Ohara Keiichiro , Nawate Shohei , Suzuki Tomoya , Yanagisawa Takaaki , Murayama Yuichi 
Published: December 2023

Abstract
We are conducting a clinical study of immunotherapy using tumor-fused dendritic cells (TFDC) as a modality of multidisciplinary treatment for patients with glioblastoma (GBM). In this study, we analyzed the additional effect of TFDC-immunotherapy for standard therapy. Newly diagnose GBM patients who treated at four of Jikei University Hospitals were analyzed in this study. Adjuvant therapy after tumor removal surgery was maintained according to the Supp's regimen. Bevacizumab (10 mg/kg, every 2 weeks) was added when a recurred tumor was confirmed. TFDC vaccine was generated from cultured tumor cells derived from autologous surgical specimen and dendritic cells from peripheral blood, and were subcutaneously administered in the cervical region for 3-14 times. All patients who had not participated in any other immunotherapy-related clinical studies were compared as a control group in a Propensity score matching analysis. The number of analyzed patients was 55 in the immunotherapy group and 35 in the control group. The 2-year survival rate and 5-year survival rate were 20.9% and 0% in the control group, respectively, while the immunotherapy group was 45.7% and 22.7%, respectively. A statistically significant difference in overall survival was observed between them (p=0.0045). There was no difference in the observed adverse events in the two groups. Specific adverse events for TFDC-immunotherapy was not observed. In the biomarker analysis, low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were suggested as biomarkers of better prognosis. We are currently analyzing IDH profile in those patients for further analysis. TFDC-immunotherapy should be adopted as one of the modality of multidisciplinary treatments for GBM because it is expected to have some additional effects for standard therapeutic reagents without adversely affecting them. Since there are a certain number of poor responders for this immunotherapy, predictive biomarkers of therapeutic efficacy are awaited.
10111-MPC-11 CLINICAL AND MOLECULAR NEUROPATHOLOGICAL FEATURES OF EPITHELIOID GLIOBLASTOMA
Authors: Adachi Junichi , Shirahata Mitsuaki , Suzuki Tomonari , Mishima Kazuhiko , Sasaki Atshushi , Nishikawa Ryo 
Published: December 2023

Abstract

BACKGROUND
Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM.

METHODS
Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. Moreover, we assayed methylation EPIC BeadChip arrays for each sample.

RESULTS
E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. Methylation-based classification did not reach E-GBM in all samples.

CONCLUSION
The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.