bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traditional Authorities and Strategies in Demands for Self-Determination
Authors: Neupert-Wentz Clara , Kelle Friederike Luise 
Published: October 2024

Abstract
Ethnic groups employ different strategies to pursue demands for self-determination. While some act within conventional channels of political contestation, others choose non-conventional strategies, including violence and rebellion. We conceive of this as a result of bargaining between group and state and argue that both sides’ institutions affect the likelihood of escalation. Specifically, groups with traditional authorities have the capacity and incentives to escalate conflicts. Only when such institutions are matched with internal accountability mechanisms can groups credibly commit so that bargaining failure and violence less likely. Similarly, states with open elections can tie their hands more effectively, and constitutional regulations of traditional authorities formalize state-group interactions, which also mitigates the effect of traditional authorities on conflict. We use new global data on groups that demand self-determination, their traditional political institutions, and their strategy choice from 2005 to 2015. We find support for our argument using various identification and estimation approaches. Groups with traditional authorities are much more likely to use violence, a finding that is not sensitive to the omission of unobserved confounders. Furthermore, this relationship is moderated by group-level audience costs and the strategic environment provided by the state. Our findings advance new perspectives on the interactions of customary and national institutions in determining subnational conflict.
Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 organization to prevent merotelic attachments
Authors: Wang Yue , Yu Wong Charmaine Yan , Yuen Karen Wing Yee 
Published: October 2024

Abstract
During cell division, the accurate capture of sister kinetochores that are built on the centromeres of chromosomes by microtubules emanating from opposite spindle poles governs faithful chromosome segregation. To ensure sister chromatids separate correctly, sister centromeres undergo resolution to achieve bi-polar orientation prior to microtubule attachments. Failure of centromere resolution increases the frequency of merotelic attachments, with microtubules from opposite poles attaching to the same sister kinetochore, causing lagging chromosome, aneuploidy, and even cancer progression. The Aurora B-mediated tension-sensing machinery to correct erroneous kinetochore–microtubule attachments has been well studied. However, preventative mechanisms to avoid merotelic attachments that occur in the earlier mitotic stage are poorly understood. In this study, we found that inactivation of mitotic kinase Aurora B/AIR-2 increases merotelic attachments in Caenorhabditis elegans. On one hand, Aurora B/AIR-2-deficient cells exhibited a delay in the occurrence of centromere resolution and a disruption in targeting condensin II components to chromatin. On the other hand, loss of Aurora B/AIR-2 results in an increased localization of centromeric proteins CENP-A/HCP-3 and M18BP1/KNL-2 as well as the kinetochore protein MIS-12 on chromatin, which may generate ectopic kinetochores causing erroneous attachments. To conclude, this study elucidated that Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 deposition to actively prevent merotely and chromosome instability in cells.
Antimicrobial Resistance in Staphylococcus aureus and Enterococcus spp. Isolates From Bloodstream Infections in Australian Children, 2013–2021
Authors: Williams Anita , Coombs Geoffrey W , Bell Jan M , Daley Denise A , Mowlaboccus Shakeel , Bryant Penelope A , Campbell Anita J , Cooley Louise , Iredell Jon , Irwin Adam D , Kesson Alison , McMullan Brendan , Warner Morgyn S , Williams Phoebe C M , Blyth Christopher C 
Published: October 2024

Abstract

Background
Rising proportions of antimicrobial resistance (AMR) have been observed in both Staphylococcus aureus and Enterococcus spp. isolates.

Methods
The Australian Group on Antimicrobial Resistance surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia. EUCAST 2022 was used for interpretation and the AMR package in R for data analysis.

Results
There were 2091 bloodstream infections (BSIs) with S. aureus and 534 enterococcal BSI episodes in children &lt;18 years old over 9 years. Three quarters of S. aureus BSI episodes were community-onset (78.3%), while more than half of enterococcal BSIs were hospital-onset (56.9%). The median age for S. aureus BSIs was 6 years, while &gt;50% of enterococcal BSIs were in children &lt;12 months old. Fifteen percent of S. aureus isolates were methicillin-resistant. Overall, 85.3% of S. aureus were resistant to penicillin, 12.5% resistant to erythromycin, 10.3% to clindamycin, and 4.7% to ciprofloxacin. Resistance to penicillin decreased over time, while clindamycin resistance increased. Resistance in Enterococcus spp. was almost entirely observed in Enterococcus faecium; only 1 Enterococcus faecalis isolate was ampicillin-resistant, and no E. faecalis isolates were vancomycin or teicoplanin-resistant. Seventy-three percent of E. faecium were resistant to ampicillin, 25.5% to vancomycin (VREfm), and 8.8% to teicoplanin.

Conclusions
Significant shifts in the epidemiology and resistance profiles of S. aureus and Enterococcus spp. BSIs in Australian children were observed, making clear the importance of age-stratified reporting in AMR data.
Use of tricortical iliac crest allograft for augmentation of depressed lateral tibial plateau fracture: a surgical technique
Authors: Schwab Pierre-Emmanuel , Bravin Daniel , Milby Joshua 
Published: October 2024

Abstract
Lateral tibial plateau fractures with significant articular depression and metaphyseal comminution in the setting of osteoporosis are challenging to manage. The subchondral bone defect and capacious cancellous void after surgical elevation of the articular surface is usually filled with nonstructural graft such as autologous cancellous bone graft, allogenic cancellous bone graft, or bone graft substitutes. Reports have shown a high rate of subsidence with these grafts when patients start to bear weight and ultimately failure of the construct. Structural grafts demonstrated stronger mechanical properties and lower subsidence rates. The purpose of this note is to describe a novel surgical technique using structural tricortical iliac crest allograft for the treatment of osteoporotic depressed lateral tibia plateau fracture.
Sex Chromosome Evolution: Hallmarks and Question Marks
Authors: Saunders Paul A , Muyle Aline 
Published: October 2024

Abstract
Sex chromosomes are widespread in species with separate sexes. They have evolved many times independently and display a truly remarkable diversity. New sequencing technologies and methodological developments have allowed the field of molecular evolution to explore this diversity in a large number of model and nonmodel organisms, broadening our vision on the mechanisms involved in their evolution. Diverse studies have allowed us to better capture the common evolutionary routes that shape sex chromosomes; however, we still mostly fail to explain why sex chromosomes are so diverse. We review over half a century of theoretical and empirical work on sex chromosome evolution and highlight pending questions on their origins, turnovers, rearrangements, degeneration, dosage compensation, gene content, and rates of evolution. We also report recent theoretical progress on our understanding of the ultimate reasons for sex chromosomes’ existence.
Mortality and associated factors in patients with systemic sclerosis-associated pulmonary hypertension with and without interstitial lung disease: A long-term follow-up study
Authors: Amikishiyev Shirkhan , Yalçınkaya Yasemin , Mammadova Konul , Aliyeva Numune , Durak Gorkem , Artim-Esen Bahar , Gül Ahmet , Bilge Ahmet Kaya , Okumuş Gulfer , Inanc Murat 
Published: October 2024

ABSTRACT

Objectives
We aimed to investigate mortality and prognostic factors in systemic sclerosis (SSc) patients with pulmonary hypertension (PH) with or without interstitial lung disease (ILD).

Methods
The associations between mortality and demographics, transthoracic echocardiography, right heart catheterization (RHC), pulmonary functional parameters at baseline, and treatment modalities were evaluated.

Results
Survival rates for PH-SSc patients (42 female, mean age 56.6 ± 13.5, median follow-up 45 months) were 91% at the first year, 75% at 2 years, and 43.1% at 5 years. The majority of the deceased patients had PH + ILD (P = .007). The PH + ILD group had more diffuse skin involvement, anti-Scl-70, high C-reactive protein, low FVC, and lower DLCO. The deceased patients had higher estimated pulmonary arterial systolic pressure (PASP), low cardiac output, and FVC values. Median survival time was significantly better in patients on combined therapy. Mortality-related factors in the PH + ILD group were decreased initial FVC, high estimated PASP, low cardiac output, deteriorated functional class, and monotherapy.

Conclusion
This is the first reported SSc-PH cohort from Turkey by a multidisciplinary team. PH is a severe complication of SSc with high mortality especially in patients with accompanying severe ILD.
NICU Music Therapy: Lessons Learned from a Randomized Trial
Authors: Germano Elizabeth , Grossoehme Daniel H , Richner Gwendolyn , Jenkins Rachel , Teal Connie M , Brown Miraides , Delahanty Douglas L , Friebert Sarah 
Published: October 2024

Abstract
Mothers of infants hospitalized in the neonatal intensive care unit (NICU) are at risk for developing acute and posttraumatic stress disorder, but mothers’ positive coping may improve with progress in the infant’s well-being. There is a need to investigate complementary therapies that increase infant well-being and decrease maternal stress. A pacifier-activated lullaby (PAL) device is one evidence-based intervention to assist premature infants by playing a few bars of a lullaby after an effective suck, improving feeding behavior and shortening the length of NICU stay. The PAL may be personalized with lullabies sung and recorded by the neonate’s mother or other family. This study’s purpose was to quantify the effect of a PAL intervention on maternal stress symptoms. The experimental PAL intervention included a singing and recording session with a board-certified music therapist with NICU certification. This was a single-site randomized trial comparing the effect of maternal voice recording versus standard conditions. A total of 245 infant–mother dyads were screened; 18 mothers consented to participate and 12 were randomized to one of three conditions: mother’s recorded lullaby for PAL administration, a generic female voice used for the PAL, and no intervention. Barriers arising during the study included lengthy enrollment processes, maternal visitation patterns, and an overly ambitious study design. Despite attempts to mitigate perceived barriers, we did not achieve the enrollment necessary to perform the intended analysis. We, therefore, present lessons learned and possible solutions for future music therapy research in the interest of transparency, reducing publication bias, and replication of problematic design issues in future trials.
JS03.6.A TUMOR ASSOCIATED MACROPHAGE DERIVED EXOSOMES MODULATE IMMUNOTHERAPEUTIC SENSITIVITY OF SHH MEDULLOBLASTOMA BY TARGETING M6A MODIFIED FOXD1
Authors: Chang Q , Liu Y 
Published: October 2024

Abstract

BACKGROUND
Medulloblastoma (MB) is the most common malignant brain tumor in children. The infiltration of tumor-associated macrophages (TAMs) in tumor microenvironment (TME) is correlated with the poor prognosis in SHH subtype of MB patients. Epigenetic alterations on RNA m6A modification were identified in this tumor. However, it remains unclear whether the TAMs infiltration in TME was correlated with the m6A modification status during tumor progression.

METHODS
The expression of m6A modification-related proteins and TAMs specific marker were assessed by immunohistochemistry in 40 SHH MB primary tumors. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen target genes affected by TAM-derived exosomes in SHH MB cells. Mechanisms of m6A-modification on target gene (FOXD1) were demonstrated by WB, qPCR, RNA half-life time and RNA immunoprecipitation assays. Combination treatment with AAV2/9-shFOXD1 and PD-1 inhibitors were performed in the NeuroD2: SmoA1 mouse model.

RESULTS
We reported for the first time that significant infiltration of TAMs was associated with decreased expression of METTL14 in primary SHH MBs. Exosomal microRNAs (miR-320e, miR-196b-5p, and miR-628-5p) released by TAMs targeted to the 3’-UTR (3’ Untranslated Region) of METTL14 in MB cells, promoting the gene’s degradation and consequently downregulating the overall m6A level in SHH MB. MeRIP-seq and RNA-seq analyses screened out Forkhead box D1 (FOXD1) as the target gene upregulated by TAMs-derived exosomes through m6A modification in MB cells, which was correlated with poor prognosis in SHH MB patients. Further experiments in vitro verified YTHDF2 can recognize m6A-modified FOXD1 and promote its mRNA degradation. Knockdown of FOXD1 in SHH MB cells significantly promoted the release of the CD8+T cell recruiting chemokines CXCL10/11. Treatment with AAV2/9-shFOXD1 significantly enhanced the anti-tumor effect of PD-1 inhibitor in NeuroD2: SmoA1 SHH MB mice.

CONCLUSION
Our study revealed the m6A modification status of SHH MBs influenced by TAMs derived exosomal miRNAs. FOXD1 promoted the malignant progression of SHH MB through m6A modification. Increased immunotherapeutic sensitivity of the combination treatment with FOXD1 knockdown and anti-PD-1 blockade in vivo shed lights on a novel therapeutic strategy of SHH MB.
JS06.5.A MERTK ON TUMOUR CELLS AND MACROPHAGES: A THERAPEUTIC OPTION FOR NF2-RELATED AND SPORADIC MENINGIOMA
Authors: Hanemann C , Dave F , Herrera K , van de Weijer L L , Henderson S , Dunn J , Singh L , Adams C L , Ercolano E , Hilton D A , Kurian K M , Maze E A , Ammoun S , Laraba L , Parkinson D B 
Published: October 2024

Abstract

BACKGROUND
Meningioma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatment.

MATERIAL AND METHODS
We analysed tumour tissue and used cell culture including 3D cultures and also PDX models applying different functional read outs after pharmacological inhibition and knock down. This was complemented by Western blots, co-IP, RNA seq and proteomic analysis.

RESULTS
We demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal formation of MERTK/TYRO3 heterocomplexes in meningioma. We demonstrate interdependency of TAM receptor expression. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitors and the AXL inhibitors. MERTK inhibition was more effective and we show an effect also in 3D tumour models as well as PDX models. Further we found that TAM receptors are expressed by tumour-associated macrophages in meningioma and that MERTK inhibition strongly depleted macrophages in meningioma.

CONCLUSION
Inhibiting MERTK is a new therapeutic option for meningioma
JS08.7.A SURGERY TRANSIENTLY DISRUPTS THE BLOOD BRAIN BARRIER OF THE GLIOBLASTOMA RESECTION MARGIN: OPPORTUNITIES FOR EARLY AND SELECTIVE POSTOPERATIVE TREATMENT
Authors: Fernandes L F , Lozano N , Peeyatu C , Ho Y , Thompson L , Kostarelos K , Kisby T 
Published: October 2024

Abstract

BACKGROUND
Resection surgery is the first line therapy for glioblastoma (GBM) that is performed in &gt;70% of patients typically within days of suspected, MRI-based diagnosis. Current standard protocols for follow-on chemo/radiotherapy have shown only modest efficacy in eliminating residual disease, with inevitable tumour recurrence. There remains a need to develop new approaches to swiftly and effectively treat post-operative residual disease to prevent the rapid progression of recurrent GBM.

MATERIAL AND METHODS
Using two syngeneic preclinical models of glioblastoma resection/recurrence (GL261 and IDH-WT glioma neurospheres), we identified a spatially and temporally restricted window of resection margin-localized blood brain barrier (BBB) disruption during the immediate and early postoperative periods. This was mapped overtime by intravenous administration of fluorescently labelled lipid nanoparticles (LNPs) and using a combination of in vivo and ex vivo imaging modalities.

RESULTS
LNPs showed a selective accumulation at the postoperative resection margin site while largely being excluded from areas of the brain with an intact BBB. From longitudinal assessment of this phenomenon, we identified a biphasic increase in LNP accumulation whereby initial BBB disruption appeared to be mediated by the surgical procedure itself (minutes post-surgery), whereas a second temporary period of disruption (2-3 days after surgery) presumably driven by a post-operative inflammatory tissue response and remodelling. Confocal analysis confirmed the presence of extravasated LNPs in the parenchyma which largely interacted with glial populations that closely associated with residual tumour tissue. Exploiting this, we performed early intravenous administration of doxorubicin chemotherapy loaded LNPs coinciding with the peak of postoperative BBB disruption and demonstrated complete inhibition of tumour recurrence from a single administration. In contrast, late administration of doxorubicin LNPs (in line with the typical clinical post-operative treatment schedule) did not achieve such profound efficacy. Notably, administration of doxorubicin alone (not encapsulated in LNP) also did not show significant efficacy highlighting the importance of this selective nanocarrier in combination with BBB disruption.

CONCLUSION
Overall, this work underscores the importance of this early post-operative timeframe for margin/residual disease selective treatments that may have been overlooked in most trials of experimental GBM medicines. Furthermore, this demonstrates that clinically approved nanomedicines could be readily repurposed for early post-operative therapy in aggressive brain tumours. Further work is warranted to develop novel nanoparticle enabled approaches for the early treatment of residual GBM toward overcoming this longstanding clinical need.
P01.11.B PATIENT-DERIVED GLIOBLASTOMA CELLS ARE CAPABLE OF FORMING TUBE-LIKE STRUCTURES IN VITRO SUGGESTIVE OF VASCULOGENIC MIMICRY
Authors: Maddison K , Bowden N A , Graves M C , Fay M , Tooney P A 
Published: October 2024

Abstract

BACKGROUND
The tube formation assay (TFA), widely used to assess the angiogenic ability of endothelial cells in vitro, involves plating endothelial cells on a basement membrane matrix layer that promotes the differentiation of the cells, observed as the formation of tubule-like structures. The extent and characteristics of the tubule network are influenced by cell seeding density, addition of growth factors, and the composition of the basement membrane matrix. Tube formation by tumour cells in vitro is considered to be an indicator of the ability of these cells to undergo vasculogenic mimicry (VM), the process by which tumour cells form functional vessel-like structures. The TFA has therefore been used to assess VM in various tumours, including glioblastoma. However, aspects of the TFA, including seeding density, basement membrane matrix, media composition, and imaging timepoint, vary greatly between previous studies of VM in glioblastoma, resulting in difficulty comparing results between studies and uncertainty relating to the conditions under which glioblastoma cells may undergo tube formation. We therefore aimed to assess the tube formation ability of multiple glioblastoma cell lines assayed under the same conditions.

MATERIAL AND METHODS
Twelve patient-derived glioblastoma cell lines were plated for TFAs at multiple seeding densities in serum-free media on a 150µL/cm2 layer of growth factor-reduced (GFR) Matrigel. Cells were imaged 2-hourly for 24 hours using an Incucyte SX5 Live-Cell Analysis Instrument in order to determine the tube formation ability and optimal seeding density of each cell line. Human umbilical vein endothelial cells (HUVECs) were used as a positive control. The Angiogenesis Analyzer plugin for ImageJ was used to quantify number of tubules, average tubule length, tubule area, and number of branch points for HUVECs and tube forming glioblastoma cells.

RESULTS
Three of the 12 glioblastoma cell lines tested were considered capable of in vitro tube formation, consistently forming tubule-like networks that morphologically resembled those formed by HUVECs within 24 hours of plating for a TFA. Network characteristics differed between HUVECs and glioblastoma cells, with the glioblastoma cells generally forming a higher number of shorter tubules, and therefore having a higher number of branch points. This did not correspond to a larger total tubule area, which was comparable between the HUVECs and glioblastoma cells.

CONCLUSION
A subset of patient-derived glioblastoma cell lines are able to form tube-like structures in vitro when grown in serum-free media on GFR Matrigel. Further experiments assessing additional TFA conditions and subsequent analyses of gene and protein expression in tube-forming glioblastoma cell lines may provide further insight into the mechanisms by which VM may be occurring.