bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic vacancy in 2D defective semiconductor In2S3 for artificial photonic nociceptor
Authors: Wang Peng , Xue Wuhong , Ci Wenjuan , Yang Ruilong , Xu Xiaohong 
Published: June 2023

Abstract
It is crucial to develop an advanced artificially intelligent optoelectronic information system that accurately simulates photonic nociceptors like the activation process of a human visual nociceptive pathway. Visible light reaches the retina for human visual perception, but its excessive exposure can damage nearby tissues. However, there are relatively few reports on visible light–triggered nociceptors. Here, we introduce a two-dimensional natural defective III–VI semiconductor β-In2S3 and utilize its broad spectral response, including visible light brought by intrinsic defects, for visible light–triggered artificial photonic nociceptors. The response mode of the device, under visible light excitation, is very similar to that of the human eye. It perfectly reproduces the pain perception characteristics of the human visual system, such as ‘threshold,’ ‘relaxation,’ ‘no adaptation’, and ‘sensitization’. Its working principle is attributed to the mechanism of charge trapping associated with the intrinsic vacancies in In2S3 nanosheets. This work provides an attractive material system (intrinsic defective semiconductors) for broadband artificial photonic nociceptors.
Coprophagy rapidly matures juvenile gut microbiota in a precocial bird
Authors: Videvall Elin , Bensch Hanna M , Engelbrecht Anel , Cloete Schalk , Cornwallis Charlie K 
Published: June 2023

AbstractCoprophagy is a behavior where animals consume feces, and has been observed across a wide range of species, including birds and mammals. The phenomenon is particularly prevalent in juveniles, but the reasons for this remain unclear. One hypothesis is that coprophagy enables offspring to acquire beneficial gut microbes that aid development. However, despite the potential importance of this behavior, studies investigating the effects in juveniles are rare. Here we experimentally test this idea by examining how ingestion of adult feces by ostrich chicks affects their gut microbiota development, growth, feeding behavior, pathogen abundance, and mortality. We conducted extensive longitudinal experiments for 8 weeks, repeated over 2 years. It involved 240 chicks, of which 128 were provided daily access to fresh fecal material from adults and 112 were simultaneously given a control treatment. Repeated measures, behavioral observations, and DNA metabarcoding of the microbial gut community, both prior to and over the course of the experiment, allowed us to evaluate multiple aspects of the behavior. The results show that coprophagy causes (a) marked shifts to the juvenile gut microbiota, including a major increase in diversity and rapid maturation of the microbial composition, (b) higher growth rates (fecal-supplemented chicks became 9.4% heavier at 8 weeks old), (c) changes to overall feeding behavior but no differences in feed intake, (d) lower abundance of a common gut pathogen (Clostridium colinum), and (e) lower mortality associated with gut disease. Together, our results suggest that the behavior of coprophagy in juveniles is highly beneficial and may have evolved to accelerate the development of gut microbiota.
Fracture and embolization of a metal stent after a frozen elephant trunk procedure
Authors: Watanuki Hirotaka , Tochii Masato , Sugiyama Kayo , Matsuyama Katsuhiko 
Published: June 2023

Abstract
The Frozenix J graft open stent graft has been available since 2014 in Japan. This stent is widely used for the frozen elephant trunk technique in many institutions, mainly for cases of acute type A aortic dissection and also for cases of a true aneurysm and chronic aortic dissection. We treated a rare case in which the metal wires of the Frozenix J graft were broken and embolized to the periphery half a year after being implanted.
Optimizing building surface retro-reflectivity to reduce energy load and CO2 emissions of an enclosed teaching building
Authors: Qi Liyan , Wang Jing 
Published: June 2023

Abstract
Building surface reflectivity determines the amount of reflected solar radiation, which indirectly affects the cooling and heating load of a building. Therefore, optimizing building surface retro-reflectivity is an effective method to reduce energy load and CO2 emissions of buildings. To analyse the optimization potential of building surface retro-reflectivity, the effect of surface reflectivity on daily, monthly and yearly energy load, as well as CO2 emissions of an educational building were simulated based on the Energyplus software. The numerical results showed that for daily energy load in four typical seasons, there was a positive correlation between the daily energy load and building surface reflectivities in January, April and October and a negative correlation in July. For monthly energy load, the building cooling and heating loads were the highest in January and August, respectively. For annual energy load, the higher the reflectivity, the lower the cooling load and the higher the heating load. When the building surface reflectivity was 0.7, the annual energy load was the least, with a value of 148.23 kWh/m2. In addition, the CO2 emission was also the lowest, with a value of 24.79 kg/m2. According to the relation between building surface reflectivities and retro-reflectivities, the optimal retro-reflectivity was 0.47.
Development of microscopic polyangiitis following idiopathic pleuroparenchymal l fibroelastosis: A case report
Authors: Fujisaki Mayuko , Higuchi Tomoaki , Konda Naoko , Hirahara Shinya , Watanabe Kotaro , Yamada Risa , Motoyama Ryo , Yamaguchi Rei , Katsumata Yasuhiro , Kawaguchi Yasushi , Harigai Masayoshi 
Published: June 2023

ABSTRACT
Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, which is characterised by pleural fibrosis and subjacent parenchymal fibroelastosis of the upper lobes. Herein, we present a case of microscopic polyangiitis (MPA) following PPFE. The patient had abnormal shadows on chest radiographs 15 years before the onset of MPA, and the patient was diagnosed with PPFE. Four years after the PPFE diagnosis, the patient was diagnosed with MPA based on persistent fever, purpura, mononeuritis multiplex, myeloperoxidase–antineutrophil cytoplasmic antibody positivity, and pathological findings of peritubular capillaritis on kidney biopsy. The patient was treated with glucocorticoids, including methylprednisolone pulse therapy and rituximab, followed by maintenance therapy with rituximab. One year after treatment, the PPFE had not worsened. PPFE occasionally occurs secondary to connective tissue disease, including MPA; however, to the best of our knowledge, this is the first report of PPFE preceding MPA. Our case suggests that PPFE, as other interstitial lung diseases, may be associated with MPA and precede the onset of MPA. The accumulation of more cases is needed to clarify the characteristics of MPA-associated PPFE.
ATRT-05. DNA DAMAGE REPAIR INHIBITOR LP-184 INHIBITS CELL GROWTH IN ATRT
Authors: Kwon Hyuk Jean , Shah Nisha , Musa Istabraq , Raabe Eric 
Published: June 2023

Abstract
Atypical teratoid rhabdoid tumor (ATRT) is a rare, aggressive pediatric brain tumor. It is characterized by inactivation of SMARCB1 gene. There is currently no standard of care for treatment. LP-184 is an analog of acylfulvene. LP-184 induces cell-cycle arrest and cell apoptosis through alkylation of DNA and RNA. Previously, LP-184 was shown to have preclinical efficacy in temozolomide-resistant human glioblastoma cell lines. Additionally, it was reported that loss of SMARB1 increases sensitivity to LP-184. Therefore, we hypothesized that LP-184 may be effective against ATRTs. We have evaluated the effect of LP-184 in multiple ATRT cell lines, including CHLA06, CHLA266, and BT37. Treatment with LP-184 showed that LP-184 inhibits cell growth from 10nM to 200nM concentrations in an ATRT cell line (CellTiter Blue assay for BT37 p&lt;0.0001 by t-test). We have identified an IC50 of 23.92nM. LP-184 induced apoptosis 96 hours after treatment in several ATRT cell lines as demonstrated by immunofluorescence for cleaved caspase-3 (CHLA06 p=0.0003 50nM vs DMSO, CHLA266 p=0.002 50nM vs DMSO, BT37 p=0.0014 50nM vs DMSO by t-test) and Western blot for c-PARP. LP-184 decreased proliferation 96 hours after treatment in several ATRT cell lines as demonstrated by immunofluorescence for Bromodeoxyuridine (BrdU) and Western blot for p-RB. Further evaluations of LP-184 treatment in vitro and in vivo are underway. Our in vitro data so far suggests that LP-184 is an effective potential therapeutic option for ATRT.
BIOL-02. MODELING BRAIN TUMORS IN VIVO AND WITH HUMAN ORGANOIDS
Authors: Tiberi Luca 
Published: June 2023

Abstract
Brain tumors are a large and heterogeneous group of neoplasms that affect the central nervous system and include some of the deadliest cancers. Almost all the conventional and new treatments fail to hinder tumoral growth of the most malignant brain tumors. This is due to multiple factors, such as intra-tumor heterogeneity, the microenvironmental properties of the human brain, and the lack of reliable models to test new therapies. Therefore, creating faithful models for each tumor and discovering tailored treatments pose great challenges in the fight against brain cancer. We have recently developed a human IPSCs-derived organoid model of pediatric medulloblastoma and pediatric high-grade glioma. These models overcome the limitations of using animal models and pave the way to gaining unprecedented new knowledge into the development of brain cancer in a human system. Nevertheless, to fill the gap in the brain cancer field it will be crucial to use patient-derived tissues. To this aim, in the next years, we will develop patient-derived organoids (PDO) of pediatric brain tumors. These organoids recapitulate several features of the primary human tumors, such as intra-tumor heterogeneity and genomic alternation. The production of PDOs will allow us to generate important new knowledge, discover of potential drug targets, and small molecules that could be exploited in early-phase clinical trials, hopefully, to develop and validate new treatments. Interestingly, the possibility of using organoids directly generated from pediatric tumors will also pave the bases for personalized therapies.
BIOL-10. MOUSE MODELING OF PEDIATRIC MYCN GLIOMA REVEALS INTRATUMORAL HETEROGENEITY INCLUDING NEURONAL AND OLIGODENDROGLIAL LINEAGE SIGNATURES
Authors: Schoof Melanie , Godbole Shweta , Albert Thomas K , Dottermusch Matthias , Walter Carolin , Ballast Annika , Qin Nan , Olivera Marlene Baca , Göbel Carolin , Neyazi Sina , Holdhof Dörthe , Kresbach Catena , Epplen Gefion Dorothea , Thaden Vanessa , Blattner-Johnson Mirjam , Modemann Franziska , Afflerbach Ann-Kristin , Eckhardt Alicia , Muenter Daniel , Struve Nina , Jones David T W , Remke Marc , Neumann Julia E , Kerl Kornelius , Schüller Ulrich 
Published: June 2023

Abstract
Pediatric glioma of the subclass MYCN are highly aggressive tumors with a median age at diagnosis of 8 years and a median survival of only 14 months. Molecularly, they frequently carry MYCN amplifications, TP53 mutations or both of these alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and both biological as well as clinical details have not been fully addressed. In order to further investigate the biology and treatment options of these tumors, preclinical models are urgently needed. Therefore, we generated a genetically engineered model by breeding hGFAP-cre::Trp53Fl/Fl::lsl-MYCN mice, which carry a loss of Trp53 and show aberrant MYCN expression in neural precursors of the central nervous system. All such mice developed aggressive forebrain tumors early in lifetime that mimic their human counterparts regarding histology, DNA methylation, and gene expression. Single cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. To find new treatment options, we performed in vitro high-throughput drug screening on both, mouse and human tumor cells. Among 640 investigated anticancer compounds, Doxorubicin, Irinotecan, and Etoposide effectively suppressed the growth of tumor cells. As FDA-approved chemotherapeutics, these compounds are used for the treatment of other pediatric brain tumors. Repurposing them for the treatment of MYCN-driven high grade glioma could achieve a rapid transition to glioma treatment. We believe that our model will pave the way to improved treatment strategies for patients with these highly aggressive tumors.
BIOL-19. DIFFUSE MIDLINE GLIOMA CEREBRAL ORGANOID MODEL AND MULTIOMICS CHARACTERIZATION
Authors: Damodharan Sudarshawn , Favreau Peter , Lebakken Connie , Dey Mahua 
Published: June 2023

Abstract
Diffuse midline glioma (DMG) are highly aggressive malignancies of the central nervous system that primarily affect the pediatric population. These tumors are historically universally fatal with no curative treatment options available. There is a need to identify more targeted and optimal treatments for these patients. Current approaches to pre-clinical therapeutic testing have been limited by many obstacles to effectively translate theses to patients. It is known that the interactions between tumors and the other components of the tumor microenvironment (TME) can change the response to therapeutic interventions. This especially holds true for brain tumors and the complex neural network encompassed within their TME. Given this, it is crucial to develop more realistic DMG models that integrate this to conduct therapeutic testing rather than relying upon conventional cell culture models. The goal of our study was to develop a three-dimensional DMG cerebral organoid model derived from human induced pluripotent stem cells (iPSCs) co-cultured with three different DMG patient-derived xenograft (PDX) cell lines to better mimic the TME for therapeutic testing. We were able to successfully integrate our three cell lines into the cerebral organoids, capturing TME interactions along with performing multiomic profiling for better characterization. We next plan to perform therapeutic testing to further validate the model and improve preclinical drug screening for DMG.
BIOL-20. BIOPROCESSING OF SURGICAL PEDIATRIC BRAIN TUMOR SPECIMENS FOR GENOME-GUIDED PERSONALIZED DRUG TESTING
Authors: Nasajpour Emon , Tran Caitlynn , Garcia Cesar , Lyle Geoff , Guinle Maria I Barros , Bagley Bryce A , Lancero Hope , Gibson Eden E , Schouten Troy , Mahaney Kelly , Vogel Hannes , Learned Katrina , Vaske Olena , Grant Gerald A , Prolo Laura M , Petritsch Claudia K 
Published: June 2023

Abstract
Novel treatment approaches are urgently needed for pediatric central nervous system (CNS) tumors as they are the leading cause of cancer-related deaths in children. A lack of research materials impedes progress towards developing such therapies. Although various brain cancer biobanks exist, these rarely store viable patient-derived tissue and cells for live cell analyses, including cell fate assays and testing for drug sensitivities. We propose that a biorepository of viable cell dissociates and tissue broadly representing CNS tumor entities overcomes these limitations.
From a combination of molecular diagnoses and histopathologic assessment of over 90 samples collected, we generated a biorepository of roughly 35 distinct entities of pediatric CNS tumors in our Stanford neuro-bioprocessing cohort. Based on the Central Brain Tumor Registry of the United States, the proportion of subtypes represented in our cohort match that of the general population with exceptions. We established a standardized bioprocessing pipeline that can be used as a template for tissue collection and model development in the broader disease context and for multiple downstream applications. Our emphasis on cryostorage of viable cells and tissue facilitates ad hoc live cell analyses. In addition to gaining a better understanding of tumor pathophysiology, we attempted a rapid bed-to-bench-to-bedside approach using comparative RNA expression profile analyses in an individual patient’s pilocytic astrocytoma. Novel drug targets were identified by analyzing RNA transcripts that are highly expressed (outliers) compared with a compendium of 12,747 brain and non-brain tumor samples. We validated outliers as drug targets using acute cell isolates, and identified a novel target in recurrent low-grade glioma. These studies illustrate that biobanking of viable patient-derived material enables developing personalized therapies with the goal of improving patient outcomes. As demonstrated here, patient-derived acute cell isolates facilitate identifying drug vulnerability, creating an opportunity for more personalized treatment of patients with CNS tumors.
DIPG-01. LIN28B EXPRESSION IN DIFFUSE MIDLINE GLIOMA
Authors: Knowles Truman , An Shejuan , Huang Tina , Qi Jin , Saratsis Amanda 
Published: June 2023

Abstract

INTRODUCTION
Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. LIN28B is an RNA binding protein expressed in a variety of cancers, which suppresses the let-7 family of microRNAs, which in turn suppresses a plethora of oncogenes. However, the role of LIN28B in DMG has not yet been explored. Therefore, we sought to determine the pattern of expression and potential function of LIN28B in DMG using rare DMG cell lines.

METHODS
All studies were performed on DMG cell lines (n=6) and controls (normal human astrocytes n=1, human neural stem cells n=1). RNA-Seq was performed using single-read sequencing at 50bp on the Illumina NextSeq 500 Sequencing System. Cells were then treated with DMSO or the LIN28B inhibitor, LI71, and submitted to functional in vitro studies, as well as RNA-Seq and Western Blot analysis. Functional pathways analysis was subsequently performed on resulting gene expression values with Ingenuity Pathways Analysis (Qiagen).

RESULTS
Differential LIN28B expression was demonstrated across cell lines, with DMG cells expressing greater LIN28B gene and protein levels compared to controls. LIN28B inhibition with small molecule inhibitor LI71 resulted in decreased cell proliferation and migration, in vitro. A total of 946 differentially expressed genes were identified between treatment groups (FC&gt;2 or &lt;-2, p&lt;0.05). Functional pathways analysis of differentially expressed genes implicated Cancer and Neurological Disease as the top disease processes, with Cellular Movement as the top molecular process in cell lines expressing LIN28B. Further, inactivation of Myc signaling was implicated in cells treated with LI71.

CONCLUSIONS
Our data demonstrates increased LIN28B expression in DMG cell lines compared with controls, with oncogenic effects on cell proliferation and migration. Further investigation of the LIN28B-let7 signaling axis is warranted in order to further explore LIN28B as a novel therapeutic target in DMG.
DIPG-08. THE LANDSCAPE OF TUMOR CELL STATES AND SPATIAL ORGANIZATION IN H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA ACROSS AGE AND LOCATION
Authors: Liu Ilon , Jiang Li , Samuelsson Erik , Salas Sergio Marco , Beck Alexander , Hack Olivia , Jeong Daeun , Shaw McKenzie , Englinger Bernhard , LaBelle Jenna , Mire Hafsa , Madlener Sibylle , Mayr Lisa , Quezada Michael , Trissal Maria , Panditharatna Eshini , Ernst Kati , Vogelzang Jayne , Gatesman Taylor , Halbert Matthew , Palova Hana , Vesela Petra , Sterba Jaroslav , Slaby Ondrej , Geyeregger Rene , Diaz Aaron , Findlay Izac , Dun Matt , Resnick Adam , Suva Mario , Jones David , Agnihotri Sameer , Ostlin Jessica , Koschmann Carl , Haberler Christine , Czech Thomas , Slavc Irene , Cotter Jennifer , Ligon Keith , Alexandrescu Sanda , Yung W K Alfred , Arrillaga-Romany Isabel , Gojo Johannes , Monje Michelle , Nilsson Mats , Filbin Mariella 
Published: June 2023

Abstract
Histone 3 lysine27-to-methionine mutations (H3-K27M) frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, thalamus, and spinal cord, presumed to be driven by the specific spatiotemporal context of these midline locations during postnatal development. While most common in the pons and at mid-childhood ages, the same oncohistone mutation is recurrently detected in adult DMGs and throughout different midline regions. The potential heterogeneity of tumors at different ages and in different anatomical locations of the midline are vastly understudied. Through dissecting the transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs - spanning the age range from 2-68 years and locations from spinal cord to thalamus - at single cell resolution, we delineate how age- and location-dependent contexts shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We identify that oligodendrocyte precursor (OPC)-like cells constitute the stem-like compartment in H3-K27M DMGs across all clinico-anatomical groups, however, depending on location, display varying levels of maturity resembling less differentiated pre-OPCs or more mature OPCs further differentiated along the oligodendroglial lineage. We further demonstrate increased mesenchymal cell states in adult tumors, which we link to age-related differences in glioma-associated immune cell compartments, in particular an increase of macrophages in adult compared to pediatric tumors. Furthermore, we resolve the spatial organization of H3-K27M DMG cell types and states in intact patient tissues, identifying a local niche of the oligodendroglial lineage. Our study provides a powerful resource for rational modeling and therapeutic frameworks taking into account determinants of age and location in this lethal glioma group.
DIPG-24. BRD4 INHIBITION AS A RADIOSENSITIZER THROUGH BLOCKING DNA REPAIR FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA
Authors: Watanabe Jun , Clutter Matt , Hoeman Christine , Amreena Sui , Abe Koki , Ishi Yukitomo , Uchida Eita , Becker Oren , Hashizume Rintaro 
Published: June 2023

Abstract
Diffuse intrinsic pontine glioma (DIPG) is one of the devastating childhood cancers. Radiation therapy (RT) remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance RT efficacy by combining it with radiosensitizing agents, though none have been successful in doing so. Given this, there is a critical need to identify effective therapeutics to enhance the RT anti-tumor activity in DIPG. Here, we identified BRD4 inhibitors as candidate radiosensitizers from a high throughput drug screening. DIPG cells show increased H3 K27 acetylation (H3K27ac) levels, which bind to BET bromodomain protein 4 (BRD4) and are strongly associated with active transcription. We tested two BRD4 inhibitors (BRD4i: AZD5153 and JQ-1) as well as genetic BRD4 depletion, and observed enhancement of radiation-induced DNA damage, confirming BRD4i as potential radiosensitizers in the treatment of DIPG. We evaluated the effects of BRD4i on gene expression using RNAseq, and observed significant inhibition of DNA-repair proteins such as BRCA1 and RAD51. CUT-RUN qPCR showed decreased H3K27ac at BRCA1 and RAD51 promoters. Combination of BRD4i and RT inhibited cell viability significantly using clonogenic survival assay, apoptosis assay, and also showed cell cycle arrest. Radiation-induced DNA double-strand break (DSB) repair was prolonged with BRD4i with high levels of gH2AX and 53BP1 likely due to inhibition of DNA-repair. In vivo studies revealed increased survival of animals treated with combination therapy of RT and BRD4i in comparison to either monotherapy. Together, these results highlight BRD4i as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.