bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-45. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
Authors: Xing Lulu , Lancero Hope , Hambardzumyan Dolores , Merson Tobias , Petritsch Claudia 
Published: November 2023

Abstract
In the central nervous system (CNS), gliomas represent almost 50% of all pediatric tumors and due to their complex histological and biological heterogeneity, aggressive standard treatment consisting of surgery and chemoradiotherapy remains ineffective. As a result, more biologically based therapies are urgently needed and this requires a deeper knowledge of the etiology and biology of gliomas, which can arise from oligodendrocyte progenitor cells (OPCs). OPCs are the most proliferative cell type in the CNS, and upon oncogenic mutations in OPCs, they exhibit defective asymmetric divisions with a concomitant increase in symmetrical renewal, leading to aberrant growth of OPCs prior to malignancy. Although OPC-like cells frequently found in human glioma significantly contribute to tumor heterogeneity and malignancy, how resident tumor-infiltrating OPCs functionally integrate into the tumor cell networks within the tumor microenvironment remains unknown. However, in order to address this critical gap in knowledge of the field, a novel mouse model of conditional OPC ablation must be used to overcome methodological challenges of most current approaches that often result in partial and transient OPC ablation, which limits our understanding of long-term function of OPCs. Here, we have successfully developed a novel pharmacogenetic model of conditional OPC ablation, eliminating 98.6% of all OPCs throughout the mouse brain for up to 12 days post ablation. This novel mouse model of complete OPC ablation can be combined with intracranial injection of tumor cells in order to reveal the longitudinal and spatial functional roles and the necessity for resident OPCs in the tumor context. Understanding the OPC-tumor cell crosstalk by using our state-of-the-art approach at both cellular and molecular levels will have significant clinical implications for improving treatment for patients with pediatric gliomas.
MODL-49. NEW MURINE GLIOBLASTOMA STEM-LIKE CELL MODELS
Authors: Kardani Kimia , Ghouse Shanawaz Mohammed , Hara Toshiro , Soda Yasushi , Stemmer-Rachamimov Anat , Wakimoto Hiroaki , Rabkin Samuel 
Published: November 2023

Abstract

BACKGROUND
There is a dearth of mouse glioblastoma (GBM) preclinical models in immunocompetent mice for the development of immunotherapeutic agents. In this study, we characterized five murine GBM stem-like cell (GSC) models derived from lentivirus induced tumors in transgenic mice that are driven by the activation of the Nf1-Ras MAP kinase signalling pathway due to HRasV12 or NF1 shRNA, and inactivation of Tp53.

METHODS
Murine GSC lines, 005, NF53, RIG, C1, and C3, were cultured as spheres in serum-free stem cell media. Whole exome sequencing (WES) was conducted to quantify single nucleotide polymorphisms (SNPs) using the C57BL/6J genome as reference. Stem cell properties were characterized by in vitro assays and tumorigenicity was examined by intracerebral implantation into C57BL/6 mice. Brain tissues were processed for histological analysis, such as immunohistochemistry, or for FACS to examine markers of stemness and tumor-infiltrating immune cells.

RESULTS
WES identified a large variation in coding sequence SNPs, likely due to the mixed backgrounds of the parental mice, with 005 having the highest number of SNPs, and C1 and C3 the lowest. All GSC lines were capable of clonogenic sphere formation, indicative of self-renewal, and showed varying levels of cell surface CD133. In vivo, all the GSCs efficiently established tumors that were histologically consistent with malignant glioma with strong CD44 expression. Median survival varied, ranging from 27 days (005) to 82 days (C1), upon 20,000-cell implantation. CD68+ macrophages were consistently dominant in the tumor microenvironment, while C1 and C3 exhibited fewer CD4+ and CD8+ T cells.

CONCLUSIONS
Despite the similar molecular strategy used to generate these GBMs, we observed a range of tumor phenotypes and immune microenvironmental profiles. These models can serve as valuable tools for studying GBM biology and exploring immunotherapeutic strategies. Keywords: Glioblastoma, glioblastoma stem-like cell (GSC), genetically engineered mouse models, Tumor microenvironment.
Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: Relation to grade, histopathology, and overall survival in the GLASS-NL cohort
Authors: van Garderen Karin A , Vallentgoed Wies R , Lavrova Anna , Niers Johanna M , de Leng Wendy W J , Hoogstrate Youri , de Heer Iris , Ylstra Bauke , van Dijk Erik , Klein Stefan , Draaisma Kaspar , Robe Pierre A J T , Verhaak Roel G W , Westerman Bart A , French Pim J , van den Bent Martin J , Kouwenhoven Mathilde C M , Kros Johan M , Wesseling Pieter , Smits Marion 
Published: November 2023

Abstract

Background
The T2-FLAIR mismatch sign is defined by signal loss of the T2-weighted hyperintense area with Fluid-Attenuated Inversion Recovery (FLAIR) on magnetic resonance imaging, causing a hypointense region on FLAIR. It is a highly specific diagnostic marker for IDH-mutant astrocytoma and is postulated to be caused by intercellular microcystic change in the tumor tissue. However, not all IDH-mutant astrocytomas show this mismatch sign and some show the phenomenon in only part of the lesion. The aim of the study is to determine whether the T2-FLAIR mismatch phenomenon has any prognostic value beyond initial noninvasive molecular diagnosis.

Methods
Patients initially diagnosed with histologically lower-grade (2 or 3) IDH-mutant astrocytoma and with at least 2 surgical resections were included in the GLASS-NL cohort. T2-FLAIR mismatch was determined, and the growth pattern of the recurrent tumor immediately before the second resection was annotated as invasive or expansive. The relation between the T2-FLAIR mismatch sign and tumor grade, microcystic change, overall survival (OS), and other clinical parameters was investigated both at first and second resection.

Results
The T2-FLAIR mismatch sign was significantly related to Grade 2 (80% vs 51%), longer post-resection median OS (8.3 vs 5.2 years), expansive growth, and lower age at second resection. At first resection, no relation was found between the mismatch sign and OS. Microcystic change was associated with areas of T2-FLAIR mismatch.

Conclusions
T2-FLAIR mismatch in IDH-mutant astrocytomas is correlated with microcystic change in the tumor tissue, favorable prognosis, and Grade 2 tumors at the time of second resection.
Comparison of Publications on Heated Tobacco Products With Conventional Cigarettes and Implied Desirability of the Products According to Tobacco Industry Affiliation: A Systematic Review
Authors: Suzuki Harumitsu , Aono Naoki , Zhang Yan , Yuri Kuniko , Bassole Epse Brou Maggy Audrey Murielle , Takemura Shigeki , Higashiyama Aya , Tabuchi Takahiro , Fujiyoshi Akira 
Published: November 2023

Abstract

Introduction
Heated tobacco products (HTPs) have been advertised as “reduced-harm” tobacco products compared to conventional cigarettes (CC); however, no direct evidence supporting HTPs being desirable for human health exists. A previous systematic review reported that evidence on HTPs published in 2017 or earlier was primarily drawn from industry-related papers. We aimed to investigate whether tobacco industry-affiliated studies are more likely to conclude that HTPs are more desirable than CC.

Methods
PubMed and Ichushi-Web were searched up to March 15, 2022, for studies on HTPs published in 2017 or after. We selected studies that assessed any measures of HTPs and CC, including secondary analyses using gray literature in English or Japanese. We excluded review articles except for a meta-analysis that met the aforementioned criteria. Data on the authors’ affiliations, grant, conflict of interest, category of research subjects, and interpretation were extracted. Research members in two groups independently assessed the papers; discrepancies were solved by discussion between the groups.

Results
Overall, 134 studies met the criteria. Eighty-seven (64.9%) of them were affiliated with the tobacco industry. Of the 134 studies, 56.3% (49/87) of the industry-affiliated studies versus 19.1% (9/47) of nonindustry-affiliated studies concluded that HTPs were more desirable than CC (p &lt; .01). No study investigated clinically relevant outcomes, such as disease occurrence.

Conclusions
Publications on HTPs in the biomedical literature from January 2017 to March 2022 were dominated by tobacco industry-affiliated studies. More than half of them concluded that HTPs were more desirable than CC compared to independent studies.

Implications
Tobacco industry advertises HTPs as “reduced-harm” tobacco products compared to CC. HTP users tend to consider HTPs as alternative tobacco products less harmful than CC (ie, products for “harm reduction”). Our results demonstrated that papers written by tobacco industry-affiliated authors concluded that HTPs were more desirable than CC compared to papers by independent authors. However, all their judgments were based on surrogate outcomes. Surrogate outcomes are not necessarily linked to clinically relevant outcomes such as disease occurrence. Further studies on HTPs using clinically relevant outcomes are warranted by independent authors from tobacco industry.
Predictors of Detectable Viremia, Outcomes, and Implications for Management of People Living With HIV Who Are Receiving Antiretroviral Therapy in Southern Nigeria
Authors: Akpan Uduak U , Nwanja Esther N , Badru Titilope , Toyo Otoyo E , Idemudia Augustine M , Sanwo Olusola , Okeke Pius Nwaokoro , Gana Bala , Idem Saade , Idiong Helen M , Khamofu Hadiza G , Bateganya Moses H 
Published: November 2023

Abstract

Background
This study examined the prevalence and factors associated with detectable viremia, as well as clinical outcomes among people with HIV (PWH) receiving antiretroviral therapy (ART) who initially achieved viral suppression in 2 southern states in Nigeria.

Methods
The retrospective cohort study used data from the electronic medical records of 96 comprehensive ART centers. PWH were followed up who achieved viral suppression (viral load [VL] ≤50 copies/mL) upon starting ART based on the first VL test. We examined the presence of detectable viremia in follow-up VL results, graded by the absolute VL count from the second and third consecutive VL tests as follows: transient viremia (second follow-up VL, 51–999 copies/mL; third, ≤50 copies/mL), persistent viremia (second follow-up VL, 51–999 copies/mL or ≥1000 copies/mL; third, &gt;50 copies/mL), and virologic failure (second and third follow-up VL, &gt;1000 copies/mL). We analyzed demographic and clinical factors associated with detectable viremia using logistic regression analysis on Stata 14.

Results
Overall, 15 050 PWH had achieved viral suppression following ART initiation (median age, 34 years; 71.3% female). On follow-up, 3101 (20.6%) had a viremic event: 11.6%, transient viremia; 8.8%, persistent viremia; 0.2%, virologic failure. Shorter duration of ART (P &lt; .001), being 0 to 14 years of age (P &lt; .001), and not being enrolled in a differentiated service delivery model (P &lt; .001) were significantly associated with detectable viremia.

Conclusions
Our study shows that people who initially attain vial suppression upon starting ART remain at risk of detectable viremia.
A New England?
Authors: Searle G R 
Published: November 2023

Abstract
G. R. Searle's absorbing narrative history breaks conventional chronological barriers to carry the reader from England in 1886, the apogee of the Victorian era with the nation poised to celebrate the empress queen's golden jubilee, to 1918, as the 'war to end all wars' drew to a close leaving England to come to terms with its price - above all in terms of human life, but also in the general sense that things would never be the same again. This was an age of extremes: a period of imperial pomp and circumstance, with a political elite preoccupied with display and ceremony, alongside the growing cult of the simple life; the apogee of imperialism with its idealization of war on the one hand, the start of the Labour Party, a socialist renaissance, and welfare politics on the other; and a radical challenging of traditional gender stereotypes in the face of the prevailing cult of masculinity. Under Professor Searle's historical microscope, all the details of daily life spring into sharp relief. Half-forgotten figures such as Edward Carpenter, Vesta Tilley, and Edward Carson take their place on stage beside Oscar Wilde, the Pankhursts and Lloyd George. Motoring and aviation, to become such an intrinsic part of life within the next decades, had their beginnings in this period as pastimes for the rich. From the wretched slums of England's great cities to their bustling docks and factories, from the grand portals of Westminster to the violent political challenges of the Ulster Unionists and the militant suffrage movement, from Blackpool's tower and beach packed with holidaymakers to the trenches of the Western Front, the energy, creativity, and often destructive turmoil of the years 1886-1918 are brought into focus in this magisterial history. THE NEW OXFORD HISTORY OF ENGLAND The aim of the New Oxford History of England is to give an account of the development of the country over time. It is hard to treat that development as just the history which unfolds within the precise boundaries of England, and a mistake to suggest that this implies a neglect of the histories of the Scots, Irish, and Welsh. Yet the institutional core of the story which runs from Anglo-Saxon times to our own is the story of a state-structure built round the English monarchy and its effective successor, the Crown in Parliament. While the emphasis of individual volumes in the series will vary, the ultimate outcome is intended to be a set of standard and authoritative histories, embodying the scholarship of a generation.
Intuition, Iteration, Induction
Authors: van Atten Mark 
Published: November 2023

Abstract
Brouwer’s view on induction has relatively recently been characterised as one on which it is not only intuitive (as expected) but functional, by van Dalen. He claims that Brouwer’s ‘Ur-intuition’ also yields the recursor. Appealing to Husserl’s phenomenology, I offer an analysis of Brouwer’s view that supports this characterisation and claim, even if assigning the primary role to the iterator instead. Contrasts are drawn to accounts of induction by Poincaré, Heyting, and Kreisel. On the phenomenological side, the analysis provides an alternative to that in Tieszen’s Mathematical Intuition, and confirms a view of Gödel on his Dialectica Interpretation.
Arabidopsis TETRASPANIN8 mediates exosome secretion and glycosyl inositol phosphoceramide sorting and trafficking
Authors: Liu Ningjing , Hou Lipan , Chen Xin , Bao Jingjing , Chen Fangyan , Cai Wenjuan , Zhu Huixian , Wang Lingjian , Chen Xiaoya 
Published: November 2023

Abstract
Sphingolipids are components of plant membranes, and their heterogeneous distribution gives different membrane systems distinct properties. For example, glycosyl inositol phosphoceramides (GIPCs), 1 major type of sphingolipids, aggregate in the outer layer of the plasma membrane (PM), as well as in extracellular vesicles (EVs), including the small (30 to 100 nm) EVs termed exosomes. How these sphingolipids are sorted and trafficked is not clear. In this work, we report that Arabidopsis thaliana TETRASPANIN8 (TET8) acts as a sphingolipid carrier and thus regulates the export of GIPCs from the Golgi apparatus. TET8 recognized the coat protein complex I (COPI) subunit γ2-COPI and moved to its proper location in the PM; this recognition required the TET8 C-terminal tail. Deleting the C-terminal tail of TET8 largely restricted its roles in GIPC transport and endosomal trafficking. Further, we show that TET8 affects EV secretion in association with GIPCs. Thus, our findings shed light on GIPC transport and the molecular machinery involved in EV biogenesis.
Long small RNA76113 targets CYCLIC NUCLEOTIDE-GATED ION CHANNEL 5 to repress disease resistance in rice
Authors: Zheng Liyu , Yu Yiyang , Zheng Ying , Wang Yaxin , Wu Na , Jiang Chunhao , Zhao Hongwei , Niu Dongdong 
Published: November 2023

Abstract
Small RNAs are widely involved in plant immune responses. However, the role of long small RNAs (25 to 40 nt) in monocot plant disease resistance is largely unknown. Here, we identified a long small RNA (lsiR76113) from rice (Oryza sativa) that is downregulated by Magnaporthe oryzae infection and targets a gene encoding CYCLIC NUCLEOTIDE-GATED CHANNEL 5 (CNGC5). The cngc5 mutant lines were more susceptible to M. oryzae than the wild type, while knocking down lsiR76113 in transgenic rice plants promoted pathogen resistance. A protoplast transient expression assay showed that OsCNGC5 promotes Ca2+ influx. These results demonstrate that OsCNGC5 enhances rice resistance to rice blast by increasing the cytosolic Ca2+ concentration. Importantly, exogenous Ca2+ application enhanced rice M. oryzae resistance by affecting reactive oxygen species (ROS) production. Moreover, cngc5 mutants attenuated the PAMP-triggered immunity response, including chitin-induced and flg22-induced ROS bursts and protein phosphorylation in the mitogen-activated protein kinase cascade, indicating that OsCNGC5 is essential for PAMP-induced calcium signaling in rice. Taken together, these results suggest that lsiR76113-mediated regulation of Ca2+ influx is important for PTI responses and disease resistance in rice.
Goblet cell interactions reorient bundled mucus strands for efficient airway clearance
Authors: Bos Meike F , Ermund Anna , Hansson Gunnar C , de Graaf Joost 
Published: November 2023

Abstract
The respiratory tract of larger animals is cleared by sweeping bundled strands along the airway surface. These bundled strands can be millimetric in length and consist of MUC5B mucin. They are produced by submucosal glands, and upon emerging from these glands, the long axis of the bundled strands is oriented along the cilia-mediated flow toward the oral cavity. However, after release, the bundled strands are found to have turned orthogonal to the flow, which maximizes their clearance potential. How this unexpected reorientation is accomplished is presently not well understood. Recent experiments suggest that the reorientation process involves bundled strands sticking to MUC5AC mucus threads, which are tethered to the goblet cells. Such goblet cells are present in small numbers throughout the airway epithelium. Here, we develop a minimal model for reorientation of bundled mucus strands through adhesive interactions with surface goblet cells. Our simulations reveal that goblet cell interactions can reorient the bundled strands within 10 mm of release—making reorientation on the length scale of the tracheal tube feasible—and can stabilize the orthogonal orientation. Our model also reproduces other experimental observations such as strong velocity fluctuations and significant slow-down of the bundled strand with respect to the cilia-mediated flow. We further provide insight into the strand turning mechanism by examining the effect of strand shape on the impulse exerted by a single goblet cell. We conclude that goblet cell–mediated reorientation is a viable route for bundled strand reorientation, which should be further validated in future experiment.
The Haunted Island: Medieval History and the Old English Elegies in Brenda Chamberlain’s Tide-race (1962)
Authors: Brooks Francesca 
Published: November 2023

Abstract
This article explores the relationship between Tide-race, a 1962 memoir by the Welsh poet and artist Brenda Chamberlain, and medieval culture and literature on Ynys Enlli. Written in the decades after the Second World War when Chamberlain had left mainland Wales, Tide-race is a memoir of the artist’s time on Enlli living with its small community of fishermen and farmers. In contrast to other works of twentieth-century island literature, I argue, Chamberlain rejected dominant, medieval patriarchal histories of Enlli, refusing to read the island as a male monastic site, or as a Welsh nationalist or cultural space. Tide-race is a medieval modern text that is deeply ambivalent about what medieval culture means for modern conceptions of identity, specifically Welshness and womanhood. Chamberlain’s late modernist work has been neglected because of her status as a Welsh woman writer working outside of the centres of modernism, and she has never been considered in the context of Medievalism Studies. By bringing archival material from the Brenda Chamberlain papers at the National Library of Wales together with the published memoir, this article brings to light an unremarked upon interest in Old English literature and traces the development of Chamberlain’s medievalism in the post-war period. Although her use of the Old English elegies—The Wanderer, The Seafarer and The Wife’s Lament—has remained unnoticed by Chamberlain’s critics, these early medieval poems are translated and adapted in her prose in ways that allow her to exorcize old grudges and challenge masculine ideals.
Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis
Authors: Na Hyun-jin , Jeon Nakyung , Staatz Christine E , Han Nayoung , Baek In-hwan 
Published: November 2023

Abstract

Study Objectives
Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant, lemborexant, and daridorexant), focusing on narcolepsy-like symptoms associated with these drugs.

Methods
Five prominent databases were searched to identify randomized controlled trials (RCTs) on this topic. Primary safety outcomes included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Excessive daytime sleepiness (EDS), sleep paralysis, and hallucinations were categorized as adverse events (AEs)-related narcolepsy-like symptoms.

Results
Eleven RCTs with 7703 patients were included. DORAs were associated with a higher risk of TEAEs (risk ratio [RR], 1.09; 95% confidence interval [CI], 1.03 to 1.15) and treatment-related TEAEs (RR, 1.69; 95% CI: 1.49 to 1.92) when compared to placebo. The DORA group exhibited a significantly higher risk of EDS (RR, 2.15; 95% CI: 1.02 to 4.52) and sleep paralysis (RR, 3.40; 95% CI: 1.18 to 9.80) compared to the placebo group.

Conclusion
This meta-analysis achieved a comparative evaluation of the clinical safety and tolerability of FDA-approved DORAs for primary insomnia, specifically focusing on AEs-related narcolepsy-like symptoms. This study contributes to understanding the safety profile of FDA-approved DORAs for treating insomnia.