bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-23. The identification and validation of plasma membrane proteins as potential therapeutic targets for histone H3 mutant paediatric high-grade gliomas.
Authors: Snary Anya , Pickering James , Rahman Ruman , Grundy Richard , Haque Farhana , Layfield Robert 
Published: June 2022

Abstract
Paediatric high grade gliomas (pHGG) are the leading cause of cancer-related death in children. Histone H3.3 mutations are an important hallmark of pHGG, but their underlying oncogenic mechanisms are incompletely understood. Towards identifying molecular effectors that may be therapeutically effective, we employed proteomic profiling and determined plasma membrane proteins of the surfactome that are differentially expressed on the surface of H3.3 mutant (G34R, G34V) compared to H3.3-wildtype human glioma cells in culture. Profiling of plasma membrane-enriched fractions identified 34 membrane proteins exclusively detected from H3 G34V mutant cells compared to H3 wild-type cells, and 10 membrane proteins exclusively detected from H3 G34R mutant cells, with 39 membrane proteins shared between both H3 G34R/V genotypes. One of these shared membrane proteins, GLUT1 (glucose transporter), has very recently been reported to be over-expressed and linked to tumour phenotypes in mouse glioma cells manipulated to carry the most common DIPG-associated H3.3-K27M mutation [Miya et al. Neuro-Oncology Advances 2021]. Here, we explore the functional significance of GLUT1 differential expression in H3.3 mutant (G34R, G34V) human glioma cells. Collective observations support a model where different H3.3 mutations converge on changes in GLUT1 expression and reinforce GLUT1 as a potential therapeutic target in paediatric high-grade gliomas.
MODL-26. Development of humanized immune system, posterior fossa A ependymoma patient-derived xenograft model
Authors: Griesinger Andrea , Lang Julie , Donson Andrew , Grimaldo Enrique , Pierce Angela , Knox Aaron , Steiner Jenna , Serkova Natalie , Ritzmann Timothy , Grundy Richard , Foreman Nicholas 
Published: June 2022

Abstract
Cellular interactions between tumor and immune cells are critical in ependymoma biology. We have shown distinct immunobiology phenotypes by ependymoma molecular subgroups, with PFA2 developing an anti-tumor immune phenotype and in contrast PFA1 tumor immune cells being pro-tumor. We recently established two fully characterized pediatric PFA1 intracranial xenograft models in NSG mice. These models, while critical for advancing PFA studies, lack the ability to make lymphocytes. To address this we have established a humanized orthotopic model of PFA1 ependymoma that are grafted to produce functional human lymphocytes. To do this, CD34+ human umbilical cord blood was injected into the cranial facial vein of newborn, irradiation immunodepleted, BRGS mice. Human immune chimerism was determined at 10 weeks by flow cytometry of peripheral blood. Next, we injected existing PDX model MAF-928_XF cells into the 4th ventricle at 12 weeks age and tumors were monitored by MRI. Initial scanning found the tumors were delayed in developing, consistent with other humanized solid tumor mouse models. Mice were euthanized between 32-34 weeks age and necropsies were performed to isolate brain, lymph nodes, blood and spleen. Human chimerism was detectable, by flow cytometry, in spleen, lymph nodes and blood, and most cells were T-cells. Human T-cells were detectable in all tumors, in proportions consistent with human disease (0.05-0.5% of CD45+). Tumors also had 35-50% mouse myeloid infiltration. Tumors were MHC I negative and MHC II positive, and PD-L1 low. Histology was consistent with human ependymoma. We are using spatial proteomics to determine cellular location and phenotype of infiltrating immune cells. Initial studies indicate this model will be usable for modeling the critical tumor-immune interactions and pre-clinically testing the next therapies in PFA ependymoma and can be easily adapted to other pediatric brain tumors in which immune factors have a critical role.
MODL-29. Molecular Landscape of a comprehensive panel of pediatric brain cancer Patient-derived orthotopic xenograft (PDOX) models inform unique targets for drug responsiveness
Authors: Braun Frank K , Brabetz Sebastian , Qi Lin , Du Yuchen , Kogiso Mari , Zhang Hui Yuan , Linday Holly , Teo Wanyee , Baxter Patricia , Su Jack M F , Adekunle Adesina , Goeun Bae , Powell Reid T , Parsons Donald W , Chintagumpala Murali , Stephan Clifford C , Pfister Stefan , Lau Ching C , Kool Marcel , Li Xiao-Nan 
Published: June 2022

Abstract
Brain tumor is a leading cause of cancer related death in children. In addition to replicating histopathology, animal models faithfully replicating genetic/epigenetic abnormalities, molecular subtypes and broad inter-tumoral heterogeneities are needed. Through direct implantation of patient surgical or autopsied tumor tissues into matching locations in the brains of SCID mice, we developed a panel of 150 PDOX mouse models. Here, we report the analysis of 74 of the 150 PDOX models, 45 matching patient tissues and 60 non-tumorigenic samples to a well-annotated reference cohort of 2,801 methylation profiles of primary brain tumors. Our data showed that the lack of tumorigenicity was neither correlated with molecular subtypes nor predicted by low cell viabilities of the patient samples. Methylation profiling identified PDOX models representing nearly a full spectrum of molecular subtypes of pediatric brain tumors including GBM, medulloblastoma, ependymoma and ATRT. Direct comparison with the original patient tumors confirmed the replication of molecular subtypes. ONCOplot [FB1] analysis of PDOX models derived from matching pairs of primary and recurrent tumors (n=8) revealed close clustering with the patient tumors. Investigation of metastatic properties was performed in 13 MB models by harvesting and sub-transplanting matching PDOX primary tumors in the cerebella and metastatic tumors in the spinal cords. To confirm the potential and power of PDOX models in preclinical drug testing, we applied fractionated radiation (2 Gy/day x 5 days) and optimized multi-agent combinatory chemotherapies in MB models of the four major subgroups. High-throughput combination drug screening with ~ 8,000 drugs in PDOX-derived GBM cell lines and primary cultures of MB PDOX cells identified a library of ~ 3,500 drugs that were active in pediatric brain tumors. In summary, this study provides detailed information on molecular subclassification of a uniquely large cohort of PDOX models to serve as essential tools for brain tumor research.
RONC-16. Proton therapy for patients with embryonal tumor with multilayered rosettes in early childhood – results of the prospective KiProReg Study
Authors: Peters Sarah , Frisch Sabine , Merta Julien , Bäumer Christian , Blase Christoph , Tippelt Stephan , von Zezschwitz Barbara , Johann Pascal , von Hoff Katja , Geismar Dirk , Timmermann Beate 
Published: June 2022

Abstract
OBJECTIVES: Embryonal tumors with multilayered rosettes (ETMR) are rare malignancies of the central nervous system occurring predominantly in early childhood. Little is known about optimal time point and target volume of radiotherapy for the respective patients. The aim of this analysis was to evaluate treatment outcome in pediatric patients with ETMR treated with Proton Therapy (PT). METHODS: Between May 2016 and August 2021, 15 patients (9 male /6 female) with ETMR received PT in our institution and were enrolled in the prospective registry study KiProReg. Patient characteristics, treatment and outcome according to standardized follow-up data were descriptively analyzed by summarizing frequencies due to small sample size. RESULTS: Median age at PT was 3.0 years (range, 1.6-4.0 years). Three patients presented with metastatic disease (M1 n=1; M2 n=1; M2/3 n=1). Eight patients were treated with salvage PT at tumor progression or recurrence. Residual disease was present in three patients at start of PT. Tumor site was infratentorial (n=3) or supratentorial (n=12). All patients received Chemotherapy (CTX) prior to PT including high dose CTX (n=9) and intrathecal CTX (n=3). Concomitant CTX with temozolomide was administered in one patient. Patients received local PT (n=8) or craniospinal irradiation (CSI) followed by a local boost (n=7). Median dose was 54.0 Gy(RBE) (range, 3.6 -59.4 Gy(RBE)). PT was terminated prematurely in one patient due to cerebral edema and disease progression. Median follow-up after diagnosis was 16.3 months (range, 6.6-65.7 months) and 5.1 months (range, 0-62.4 months) after PT. Four patients treated for salvage experienced disease progression within three months after PT, three of them deceased. CONCLUSION: Preliminary results suggest promising outcomes for childhood ETMR after PT, especially in patients treated at initial diagnosis. Longer follow-up and larger cohorts are desirable to assess long-term survival and necessity of CSI.
Trends in Hospital Admissions for Chronic Obstructive Pulmonary Diseases After Comprehensive Tobacco Control Policies in Beijing, China
Authors: Wu Yiqun , Wang Zijing , Zheng Yunting , Wang Mengying , Wang Siyue , Wang Jiating , Wu Junhui , Wu Tao , Chang Chun , Hu Yonghua 
Published: June 2022

Abstract

Introduction
Only a few studies have examined the effectiveness of tobacco control policies on respiratory conditions, and the results were less consistent. The 2015 Beijing tobacco control policy package incorporating all six components of MPOWER has been implemented since Jun 2015. The present study aimed to evaluate the impact of a comprehensive tobacco control policy package on hospital admissions for chronic obstructive pulmonary disease (COPD) in Beijing, China.

Aims and Methods
An interrupted time-series study was conducted based on the hospital admission information for about 18 million residents, who were covered by the Beijing Medical Claim Data for Employees from January 2013 to June 2017. The average percentage change of COPD hospital admission rates and reductions in hospital admission numbers were estimated by segmented Poisson regression models.

Results
There were 54 040 COPD hospital admissions with a crude rate of 67.2 per 100 000 residents during the observational period. After the implementation of the policy package, the hospital admission rates of COPD were reduced by −14.7% (95%CI: −17.8%, −11.5%) immediately. The secular trend was slowed down by −3.0% (95% CI: −5.6%, −0.4%) annually. A total of 5 581 reductions in COPD hospital admissions were estimated during the 25 months post-law period, accounting for 17.5% (95% CI: 12.5%, 22.5%) of overall COPD hospital admissions. More reductions were shown in males and those aged over 65 years old.

Conclusions
The results indicated significant protections against hospitalization of COPD after the 2015 Beijing comprehensive tobacco control policy package. The results provide support for public health benefits for respiratory conditions from WHO-recommended tobacco control measures.

Implications
Only a few studies have examined the effectiveness of tobacco control policies on respiratory conditions, and the results were less consistent. Based on medical records for about 18 million residents, this study showed an association between comprehensive tobacco control policies and significant reductions of hospital admissions for chronic obstructive pulmonary disease. The results provide support for public health benefits for respiratory conditions from WHO-recommended tobacco control measures.
Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease
Authors: Khan Farhan , Allehebi Ziyad , Shabi Yahya , Davis Ian , LeBlanc Jason , Lindsay Robbin , Hatchette Todd 
Published: June 2022

Abstract
The modified 2-tier testing algorithm (MTTT) for Lyme disease (LD) has been approved by the US Food and Drug Administration. In this study, we show that the MTTT detected 28% more cases of early infection compared with the standard 2-tier algorithm while retaining high specificity in a region with a high incidence of LD.
A Showcase of Igneous Processes in the Urumieh-Dokhtar Magmatic Arc: the Miocene-Quaternary Collisional Magmatism of the Bijar-Qorveh Area, Northwest Iran
Authors: Fedele Lorenzo , Rahimzadeh Bahman , Salari Giulia , Agostini Samuele , Masoudi Fariborz , Lustrino Michele 
Published: June 2022

Abstract
The Cenozoic Arabia–Iran continental collision was associated with emplacement of a large variety of magmatic rock types. This aspect is particularly evident in the Bijar-Qorveh area of NW Iran, where Miocene andesitic to rhyolitic rocks and Quaternary basic alkaline rocks crop out. The Miocene intermediate to acid products show radiogenic Sr and Pb isotopic compositions (87Sr/86Sri 0.70531–0.71109, 206Pb/204Pb 18.71–19.01, 207Pb/204Pb 15.66–15.73, 208Pb/204Pb 38.76–39.14), coupled with unradiogenic Nd isotopic ratios (143Nd/144Ndi 0.51223–0.51265). These characteristics, together with primitive mantle-normalised multielemental patterns resembling ‘subduction-related’ geochemical fingerprints, are considered ultimately derived from the Iranian plate mantle wedge, metasomatised during previous NE-directed Neothetyan Ocean subduction. The alkali-rich andesitic and dacitic rocks evidence both closed- and open-system differentiation, as typically observed for collisional settings in general. Both rock types display a high Sr/Y (37–100) and La/Yb (29–74) ‘adakitic’ signature that it is interpreted here with plagioclase (± amphibole) accumulation or melting of local mafic crustal rocks. Open-system processes involve recycling of crustal cumulates for pyroxene-rich andesite and biotite-rich dacite varieties and low-degree partial melting of the local crust for rhyolites. A radical change occurred during the Quaternary, when SiO2-understaturated to SiO2-saturated poorly evolved rocks (basanites, tephrites, alkaline and subalkaline basalts) were emplaced. The complete change of mantle sources suggests a phase of local extensional tectonics related with WNW-ESE right-transcurrent faults. The major oxide, as well as incompatible trace element and Sr-Nd-Pb isotopic fingerprint of these younger rocks is more akin to that of intraplate magmas, but still bearing some evidences for a variable contribution from a ‘subduction-modified’ mantle source. The NW-trend of increasing involvement of this subduction component is indicative of the strong tectonic control on magmatism. Additional lithotypes indicate the presence of open-system differentiation and remelting processes in the youngest phase of magmatic activity.
Effects of Trauma and Postmigration Stress on Refugee Women’s Health: A Life Course Perspective
Authors: Sangalang Cindy C , Vang Cindy , Kim Bum Jung , Harachi Tracy W 
Published: June 2022

Abstract
Trauma exposure and postmigration stress are associated with adverse health outcomes among refugees, yet the relative effect of these factors for subgroups of refugees and those resettled long-term remains unclear. Drawing on life course theory, this study evaluated the associations between war trauma, postmigration stress, and health among Southeast Asian refugee women in the United States, and whether these patterns differ across the life span. A community sample of Vietnamese and Cambodian refugee women aged 30–72 years (N = 293) reported mental and physical health outcomes, conflict-based trauma exposure, and postmigration measures of discrimination and community violence. Both trauma exposure and discrimination were associated with mental and physical health problems, with the relative effect of each stressor varying across specific health outcomes; community violence was associated with poorer mental health. Age moderated the effect of trauma exposure across health outcomes, with stronger associations between trauma and health for older women in particular. Findings provide support for the influence of trauma exposure and the importance of postmigration stressors on health across the life span for refugees. Attending to age group differences in the effects of these stressors, and to subgroups such as women, has implications for interventions addressing the long-term health of refugee populations.
RGDX1X2 motif regulates integrin αvβ5 binding for pluripotent stem cell adhesion
Authors: Yamada Yuji , Onda Toru , Hagiuda Ayami , Kan Ryuji , Matsunuma Masumi , Hamada Keisuke , Kikkawa Yamato , Nomizu Motoyoshi 
Published: June 2022

AbstractThe arginine‐glycine‐aspartic acid (RGD) motif is a cell adhesion sequence that binds to integrins. Some RGD‐containing peptides promote adhesion of both embryonic stem cells and induced pluripotent stem cells (iPSCs); however, not all such RGD‐containing peptides are active. In this study, we elucidated the role of RGD‐neighboring sequences on iPSC adhesion using diverse synthetic peptides and recombinant proteins. Our results indicate that iPSC adhesion requires RGDX1X2 sequences, such as RGDVF and RGDNY, and that the X1X2 residues are essential for the adhesion via integrin αvβ5 but not αvβ3. iPSCs express integrin αvβ5 but not αvβ3; therefore, iPSC adhesion requires the RGDX1X2‐containing sequences. The importance of the X1X2 residues was confirmed with both HeLa and A549 cells, which express integrin αvβ5 but not αvβ3. Analysis of RGD‐neighboring sequences provides important insights into ligand‐binding specificity of integrins. Identification of integrin αvβ5‐binding motifs is potentially useful in drug development, drug delivery, cell culture, and tissue engineering.
Experimental Pain Phenotype Profiles in Community-dwelling Older Adults
Authors: Wilson Abigail T. , Johnson Alisa J. , Laffitte Nodarse Chavier , Hoyos Lorraine , Lysne Paige , Peraza Julio A. , Montesino-Goicolea Soamy , Valdes-Hernandez Pedro A. , Somerville Jessie , Bialosky Joel E. , Cruz-Almeida Yenisel 
Published: June 2022

Objectives:
Pain sensitivity and the brain structure are critical in modulating pain and may contribute to the maintenance of pain in older adults. However, a paucity of evidence exists investigating the link between pain sensitivity and brain morphometry in older adults. The purpose of the study was to identify pain sensitivity profiles in healthy, community-dwelling older adults using a multimodal quantitative sensory testing protocol and to differentiate profiles based on brain morphometry.

Materials and Methods:
This study was a secondary analysis of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study. Participants completed demographic and psychological questionnaires, quantitative sensory testing, and a neuroimaging session. A Principal Component Analysis with Varimax rotation followed by hierarchical cluster analysis identified 4 pain sensitivity clusters (the “pain clusters”).

Results:
Sixty-two older adults ranging from 60 to 94 years old without a specific pain condition (mean [SD] age=71.44 [6.69] y, 66.1% female) were analyzed. Four pain clusters were identified characterized by (1) thermal pain insensitivity; (2) high pinprick pain ratings and pressure pain insensitivity; (3) high thermal pain ratings and high temporal summation; and (4) thermal pain sensitivity, low thermal pain ratings, and low mechanical temporal summation. Sex differences were observed between pain clusters. Pain clusters 2 and 4 were distinguished by differences in the brain cortical volume in the parieto-occipital region.

Discussion:
While sufficient evidence exists demonstrating pain sensitivity profiles in younger individuals and in those with chronic pain conditions, the finding that subgroups of experimental pain sensitivity also exist in healthy older adults is novel. Identifying these factors in older adults may help differentiate the underlying mechanisms contributing to pain and aging.
Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice
Authors: Xie Jiawei , Li Hongmei , Li Shuai , Li Jianling , Li Yalan 
Published: June 2022

Abstract:
Sevoflurane, a widely used inhalation anesthetic, has been shown to be cardioprotective in individuals with sepsis and myocardial dysfunction. However, the exact mechanism has not been completely explained. In this study, we performed whole-transcriptome profile analysis in the myocardium of lipopolysaccharide-induced septic mice after sevoflurane pretreatment. RNA transcriptome sequencing showed that 97 protein coding RNAs (mRNAs), 64 long noncoding RNAs (lncRNAs), and 27 microRNAs (miRNAs) were differentially expressed between the lipopolysaccharide and S_L groups. Functional enrichment analysis revealed that target genes for the differentially expressed mRNAs between the 2 groups participated in protein processing in the endoplasmic reticulum, antigen processing and presentation, and the mitogen-activated protein kinase signaling pathway. The bioinformatics study of differentially expressed mRNAs revealed that 13 key genes including Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b are related to the heart or inflammation. Furthermore, the competing endogenous RNA network revealed that 3 of the 13 key genes established the lncRNA–miRNA–mRNA network (ENSMUST00000192774 --- mmu-miR-7a-5p --- Hspa1b, TCONS_00188587 --- mmu-miR-204-3p --- Aff3 and ENSMUST00000138273 --- mmu-miR-1954 --- Ppp1r16b) may be associated with cardioprotection in septic mice. In general, the findings identified 11 potential essential genes (Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b) and mitogen-activated protein kinase signaling pathway involved in sevoflurane-induced cardioprotection in septic mice. In particular, sevoflurane may prevent myocardial injury by regulating the lncRNA–miRNA–mRNA network, including (ENSMUST00000192774—mmu-miR-7a-5p—Hspa1b, TCONS_00188587—mmu-miR-204-3p—Aff3, and ENSMUST00000138273—mmu-miR-1954—Ppp1r16b networks), which may be a novel mechanism of sevoflurane-induced cardioprotection.
Analysis of the Reasons for the Discontinuation of Orthokeratology Lens Use: A 4-Year Retrospective Study
Authors: Ma Lina , Xu Man , Wang Jing , Niu Xiaoguang 
Published: June 2022

Purpose:
Although orthokeratology has a positive effect on myopia control, some patients discontinue orthokeratology lens use. This study analyzed the data of all patients who had been fitted with an orthokeratology lens in the past 4 years and the reasons for discontinued lens use, with the aim of improving the prevention and control of myopia.

Methods:
This retrospective study analyzed the data of patients, aged 8 to 18 years, fitted with orthokeratology lenses from 2017 to 2020. The ametropic spherical lens powers ranged from −6.00 D to −0.75 D, and the cylindrical lens powers were all more than −1.50 D. The reasons for discontinuation of lens wear were analyzed and compared. The period of lens wear (median [range]) was 24 (13.5–34.5) months.

Results:
A total of 2,499 patients' files were retrieved. The duration of lens wear was 24 (13.5–34.5) months. A total of 50 patients discontinued lens use, including 25 patients (50.0%) who could not adhere to lens use for various reasons, nine patients (18.0%) with a short sleep time, eight patients (16.0%) with economic difficulties, and five patients (10.0%) who experienced a poor effect after wearing the lenses. Corneal infiltrates affected lens use in three patients (6.0%). In addition, 30 patients underwent surgical correction when they reached adulthood.

Conclusion:
Although orthokeratology lenses are effective and safe, there are still a small number of patients who discontinued lens use for various reasons. Adherence and precautions should be emphasized during the process.