bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbial-driven nitrogen cycle and its relevance for plant nutrition
Authors: Koch Hanna , Sessitsch Angela 
Published: June 2024

Abstract
Nitrogen (N) is a vital nutrient and an essential component of biological macromolecules such as nucleic acids and proteins. Microorganisms are major drivers of N-cycling processes in all ecosystems, including the soil and plant environment. The availability of N is a major growth-limiting factor for plants and it is significantly affected by the plant microbiome. Plants and microorganisms form complex interaction networks resulting in molecular signaling, nutrient exchange, and other distinct metabolic responses. In these networks, microbial partners influence growth and N use efficiency of plants either positively or negatively. Harnessing the beneficial effects of specific players within crop microbiomes is a promising strategy to counteract the emerging threats to human and planetary health due to the overuse of industrial N fertilizers. However, in addition to N-providing activities (e.g. the well-known symbiosis of legumes and Rhizobium spp.), other plant–microorganism interactions must be considered to obtain a complete picture of how microbial-driven N transformations might affect plant nutrition. For this, we review recent insights into the tight interplay between plants and N-cycling microorganisms, focusing on microbial N-transformation processes representing N sources and sinks that ultimately shape plant N acquisition.
Impact-induced deformation away from the impact point on small asteroids
Authors: Liu P -Y , Campo Bagatin A , Benavidez P G , Richardson D C 
Published: June 2024

ABSTRACT
We investigated the propagation of energy and momentum inside a small gravitational aggregate asteroid following a hypervelocity impact, comparable to NASA’s Double Asteroid Redirection Test (DART) on asteroid Dimorphos. We show that the impact energy damps rapidly inside different kinds of granular structures, unable to reach the antipodal hemisphere of the impact. However, global reshaping of the asteroid after the formation of a sizeable (${\gt}1/3$ of target size) crater causes meter-range displacement of boulders on the antipodal hemisphere due to mass rearrangement to achieve a new equilibrium shape. As a result, a surface depression opposite to the crater is formed, which may produce some surface refreshment. The boulder mass ejection following the synthetic DART-like impact is estimated to be at least $0.1\, {{\ \rm per\ cent}}$ of the mass of the Dimorphos-like target, in agreement with recent detections of boulders ejected from the actual DART impact.
A Relational View of Homosexuality
Authors: Cordeiro-Rodrigues Luís 
Published: June 2024

Abstract
Homosexuality is criminalised and socially condemned in many places in Africa. This fact seems to suggest that African moral philosophy would likely render homosexuality immoral. Indeed, some of the African philosophical literature tries to suggest that homosexuality is morally wrong. Contrasting with this view, in this article, I will show that Afro-communitarian ethics implies that homosexuality is morally permissible and, indeed, can be an excellent way to promote social harmony. I defend this theory by drawing out the implications of social harmony, and also respond to potential objections from African intellectuals and new natural law theorists.
Changing the Frame: New Epistemic Frameworks and Social Transformation in African Feminist Theory
Authors: Graness Anke , Kopf Martina 
Published: June 2024

Abstract
This article discusses African feminist approaches to decolonization and social transformation. In recent years, there has been a significant shift in African feminist scholarship towards African concerns and Africa-centered solutions. Today’s turn to Indigenous knowledge, social structures, and gender relations is no longer just about shedding light on the precolonial past, but about fundamentally changing the epistemic framework in the sense of developing alternative epistemologies beyond the dominant ‘Western’ framework. But what is meant by ‘alternative epistemologies’? How do African feminist thinkers conceptualize social change today? And how do they relate epistemic and social change in their thinking? These questions are explored in this article, focusing on work by Sylvia Tamale (Uganda), Wangari Maathai (Kenya), and Anthonia Kalu (Nigeria) and drawing on the discourse of ecofeminism and Ubuntu as two models of alternative epistemologies.
A new anti-CRISPR gene promotes the spread of drug-resistance plasmids in Klebsiella pneumoniae
Authors: Jiang Chunyu , Yu Chengzhi , Sun Shuyi , Lin Jiajia , Cai Mufeng , Wei Zhenquan , Feng Lingling , Li Jianhui , Zhang Yan , Dong Ke , Guo Xiaokui , Qin Jinhong , Zhang Yu 
Published: June 2024

Abstract
The Klebsiella pneumoniae (K. pneumoniae, Kp) populations carrying both resistance-encoding and virulence-encoding mobile genetic elements (MGEs) significantly threaten global health. In this study, we identified a new anti-CRISPR gene (acrIE10) on a conjugative plasmid with self-target sequence in K. pneumoniae with type I-E* CRISPR-Cas system. AcrIE10 interacts with the Cas7* subunit of K. pneumoniae I-E* CRISPR-Cas system. The crystal structure of the AcrIE10-KpCas7* complex suggests that AcrIE10 suppresses the I-E* CRISPR-Cas by binding directly to Cas7 to prevent its hexamerization, thereby preventing the surveillance complex assembly and crRNA loading. Bioinformatic and functional analyses revealed that AcrIE10 is functionally widespread across diverse species. Our study reports a novel anti-CRISPR and highlights its potential role in spreading resistance and virulence among pathogens.
Modelling developments in consciousness within a multidimensional framework
Authors: Hansen Mads Jørgensen 
Published: June 2024

Abstract
A recent advancement in consciousness science has been the introduction of a multidimensional framework of consciousness. This framework has been applied to global states of consciousness, including psychedelic states and disorders of consciousness, and the consciousness of non-human animals. The multidimensional framework enables a finer parsing of both various states of consciousness and forms of animal consciousness, paving the way for new scientific investigations into consciousness. In this paper, the multidimensional model is expanded by constructing temporal profiles. This expansion allows for the modelling of changes in consciousness across the life cycles of organisms and the progression over time of disorders of consciousness. The result of this expansion is 2-fold: (i) it enables new modes of comparison, both across stages of development and across species; (ii) it proposes that more attention be given to the various types of fluctuations that occur in patients who are suffering from disorders of consciousness.
A novel approach to induce early remission in high-risk primary membranous nephropathy
Authors: Kochoyan Zinaida , Dobronravov Vladimir A 
Published: June 2024

ABSTRACT

Background
This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN).

Methods
We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by Month 12 and the time to remission.

Results
In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ .009) and the CSA group (50% and 24%, P ≤ .003). The median time to OR [2.8 (1.6–3.9) months] was shorter compared with RTX [7.1 (3.4–17.5) months, P = .008] and CSA [7.3 (6.0–13.6) months, P &lt; .001]. In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI 2.8–9.6) and 4.8 (95% CI 2.2–10.3), respectively. Propensity score–matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years.

Conclusions
RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.
BIOM-10. EXAMINATION OF GROWTH DIFFERENTIATION FACTOR 15 (GDF15) EXPRESSION AS A POTENTIAL PROGNOSTIC BIOMARKER IN PEDIATRIC BRAIN TUMORS
Authors: Marlowe Elizabeth , Ferguson Michael J , Marshall Mark S , Runco Daniel V 
Published: June 2024

Abstract

BACKGROUND
Childhood brain tumors remain a leading cause of death with significant treatment-related morbidity and mortality, including disproportionate rates of altered metabolism, neuropathy, and poor quality-of-life. Growth Differentiation Factor 15 (GDF15), a circulating cytokine released by tissue injury, mediates nausea, vomiting, and anorexia, and promotes tumor growth, angiogenesis, and metastasis in adult cancers, predicting worse progression-free survival in adults with low-grade gliomas. Despite adult cancer data, GDF15 remains unexplored in children. Published pilot data demonstrate higher circulating GDF15 in children with cancer compared to healthy controls, but GDF15 expression has not been studied in pediatric brain tumors. We present GDF15 tumor tissue expression with tumor type, grade, metastasis, and progression to inform future study of GDF15’s role in pediatric brain tumors.

METHODS
Single-center retrospective review of 64 pediatric brain tumor specimens collected through our Precision Genomics Program. GDF15 RNA expression (normalized to ß-actin tissue expression) was log-transformed. Mean GDF15 expression based on diagnosis was compared (using ANOVA) and two-sample t-tests were used to compare metastatic, progressive, and high-grade disease.

RESULTS
Highest mean GDF15 expression was seen in medulloblastoma (1.96+0.66, N=3) and lowest in low-grade glioma (0.79+0.26, N=27), but groups were not statistically different (p=0.29). GDF15 expression was higher in progressive (1.46+0.22) versus non-progressive disease (0.76+0.24, p=0.04). Although not statistically different, GDF15 expression was higher in high-grade (1.43+0.27) compared to low-grade (1.03+0.21, p=0.24) and metastatic (1.80+0.44) versus non-metastatic disease (1.06+0.17, p=0.08).

CONCLUSIONS
This ongoing work suggests variable GDF15 expression in different pediatric brain tumors and may suggest GDF15 mediates disease progression. GDF15 may play a role in metastatic or high-grade disease, but further study is needed with larger disease-specific cohorts. We demonstrate feasibility of utilizing existing genomic data and are pursuing further characterizing these potential differences through international public databases (i.e., Children’s Brain Tumor Network).
CNSC-04. EXPLORATION OF INTERCELLULAR NETWORKS IN EPENDYMOMA REVEALS POTENTIAL THERAPEUTIC VULNERABILITIES
Authors: Sundheimer Julia K , Rettenmeier Johanna , Volz Stefanie , Bamberg Leonhard V , Federico Aniello , Azorín Daniel D , Ertel Paula , Heuer Sophie , Scheuermann Sophia , Seitz Christian , Winkler Frank , Kool Marcel , Pfister Stefan M , Maaß Kendra K , Pajtler Kristian W 
Published: June 2024

Abstract

BACKGROUND
Aggressive ependymoma (EPN) exhibit primary and secondary radio- and chemotherapy resistance with the poorest prognosis in the pediatric groups PF-EPN-A and ST-EPN-ZFTA. Recently, tumor cell networks formed by membrane protrusions, such as tunneling nanotubes (TNT) or tumor microtubes (TM), have been identified in other glial brain tumors. These structures facilitate intercellular hierarchical Ca2+-communication and contribute to therapy resistance. Previous data from our group suggested enhancer-regulated Ca2+-communication to be essential in EPN. This study aims to further characterize intratumoral interactions and to understand potential correlations between tumor cell connections and treatment resistance in EPN.

METHODS
Intercellular connections in EPN patients and model systems were characterized by scanning electron microscopy, immunofluorescence and ultra-high content imaging. Transcriptomic and proteomic data were analyzed to identify potential targetable vulnerabilities within network dynamics. Candidates were functionally validated in cell culture models applying Ca2+ live cell imaging.

RESULTS
Connectivity-related terms such as microtube-based movement or microtube bundle formation showed increased expression in EPN transcriptome data compared to healthy controls. EPN networks were found to be build of TM- and TNT-like structures with a higher abundance of TNT-like structures in PF-EPN-A compared to ST-EPN-ZFTA. All networks showed strong Nestin-positivity in cells, mouse models and human tumor tissue of ST-EPN-ZFTA and PF-EPN-A. Thrombospondin-1, a matricellular protein enhancing TMs in glioma cells, was strongly enriched in ST-EPN-ZFTA patients. The gap junction channel connexin 43, connecting glioma cells, was highly upregulated in PF-EPN-A. Active electrochemical communication was observed between ST-EPN-ZFTA cells performing Ca2+ imaging. Moreover, inhibition of T-type Ca2+ channels impaired intercellular signaling, leading to network perturbation in vitro.

CONCLUSIONS
Our study revealed the importance of gap junction-coupled networks for communication of aggressive EPN cells. Targeted disconnection of the EPN-specific network as demonstrated for Ca2+ channel inhibition suggests a new avenue for therapeutic strategies in EPN to overcome resistance.
CP-08. THE CLINICAL CHARACTERISTICS OF CHILDREN WITH CRANIOPHARYNGIOMA AND THEIR MANAGEMENT IN UGANDA: A RETROSPECTIVE REVIEW
Authors: Katasi Victoria Mwebe , Munube Deogratius , Chintagumpala Murali , Naitala Ronald , Kasirye Phillip , Muwonge Peter Wasswa , Lubega Joseph , Zungu Jennifer , Nabbagala Cathy , Akullo Anne , Nakirulu Annet , Namazzi Ruth , Ssekabunga Julie , Ssenyonga Peter , Onen Justin , Wegoye Emmanuel 
Published: June 2024

Abstract

BACKGROUND
Craniopharyngiomas are benign brain tumors that mostly arise in the sellar/suprasellar region. Histologically though benign, these tumors can locally infiltrate with involvement of surrounding structures. They have a 5-year survival rate of above 80% in High Income Countries (HIC). Craniopharyngioma management includes surgery, radiotherapy and intracystic treatments and requires a multi-disciplinary team. The morbidity associated with treatment must be weighed against tumor recurrence and quality of life after treatment. Endocrine deficiencies, especially growth hormone deficiency and visual deficits are common presenting features.

OBJECTIVE
To describe the clinical characteristics and management of children with craniopharyngioma managed at Mulago National Referral Hospital from March 2019 to December 2023.

METHODOLOGY
A retrospective descriptive study was conducted among patients&lt; 18 years of age, admitted to the Mulago National Referral Hospital (MNRH) from March 2019 to December 2023 with a radiological diagnosis of a craniopharyngioma.

RESULTS
A total of 151 children with a diagnosis of a brain tumor during this period were identified and of these 40 (26%) were diagnosed with craniopharyngioma. The median age was 8.4 years and 22 (55%) were males. Only 2 children had maximal safe resection (sub-total resection), one of whom later received adjuvant external beam radiotherapy. Thirty-eight patients had insertion of ommaya reservoirs as their tumors were predominantly cystic. Two patients received intracystic bleomycin and 11 received radical external beam radiotherapy. Twenty-seven patients had no additional therapy after ommaya reservoir placement. Fifteen (39%) of the patients had endocrine deficits with hypothyroidism, hypocortisolism and growth hormone deficiency being the most common. The median follow-up time was 1.45 years. The overall survival was 67.5%, 95%CI(42.5-83.5).

CONCLUSION
Management of patients with craniopharyngioma in Uganda is mostly conservative with the aim of intervention to preserve quality of life. Limited access to radiation therapy contributed to the poorer survival compared to HIC.
DIPG-08. PROBING THE BLOOD-BRAIN-TUMOR-BARRIER WITH A MICROVASCULAR MODEL OF DIFFUSE MIDLINE GLIOMA
Authors: Bennett Kimberly R , Teboh Tessy , Hajal Cynthia , Kamm Roger D , Hammond Paula T , Straehla Joelle P 
Published: June 2024

Abstract

BACKGROUND
Pediatric diffuse midline glioma (DMG) is a uniformly fatal brain tumor in children, with most patients surviving less than 12 months. Current treatment for DMG is limited, and outcomes for this tumor have not improved. The blood-brain-barrier (BBB) remains a key challenge for DMG therapeutics, preventing most drugs from entering brain tissue. Functional characterization of the blood-brain-tumor-barrier (BBTB) – the interaction between tumors and BBB vasculature – remains largely unexplored for DMG. There is a need for a preclinical model of DMG that can probe the functional, physiological, and biological properties of the BBTB in vitro as a platform to evaluate therapeutic efficacy that is representative of human physiology.

METHODS
To generate an in vitro model of DMG with human microvasculature (DMG-BBTB model), we co-cultured DMG neurospheres, human brain microvascular endothelial cells, human brain vascular pericytes, and human astrocytes. Cells are simultaneously seeded into microfluidic devices at varied concentrations within a fibrin matrix. Self-assembled microvascular networks are formed within 7-8 days and used for downstream functional and phenotypic assays.

RESULTS
Vascular morphology and solute permeability in microvascular networks are influenced by cell identity, growth pattern, and relative concentration. We show that DMG neurospheres exhibit different patterns of growth when co-cultured as uniform spheroids versus single cells in suspension. Devices representing each growth pattern are further characterized for paracellular diffusion and permeability compared to devices without DMG cells through perfusion of high molecular weight dextran. Permeability values are correlated to biologic features such as the abundance and localization of junctional proteins and transporters.

CONCLUSIONS
We developed a platform to evaluate the microvasculature of the DMG BBTB as a tool to develop new therapies informed by vascular biology. We probed the functional, physiological, and biological properties of the human DMG BBTB in vitro, and in ongoing work are assessing approved and experimental therapeutics.
DIPG-23. SAFETY AND TECHNICAL YIELD OF BRAINSTEM BIOPSIES IN CHILDREN – AN UPDATED META-ANALYSIS OF 1000 CASES
Authors: Sheikh Shehryar R , Patel Neha J , Recinos Violette 
Published: June 2024

Abstract

BACKGROUND
Brainstem tumors represent ~10% of pediatric brain tumors, ~80% of these are diffuse intrapontine gliomas (DIPG, primarily WHO Grade 4 midline glioma, H3 K27M-mutant). Given invariably poor prognosis in these cases, there continues to be immense variation (across the US and internationally) in performing biopsy of these lesions as opposed to making a presumptive diagnosis based on MRI. Several multi-center studies in recent years have aimed to show the safety profile of biopsy but an updated meta-analysis is lacking.

METHODS
We found 29 studies of pediatric brainstem biopsy in the last 20 years (2003-2023), representing data from 1002 children. We applied meta-analysis of proportions using a random-effects model to generate point estimates, confidence intervals, and measures of heterogeneity.

RESULTS
87% of procedures were stereotactic needle biopsies (of these, 62% with a frame, 14% without frame, and 24% robotic.) Biopsy yield (i.e. the rate at which biopsy resulted in a tissue diagnosis) was 94% (95% CI 92-97). Temporary complications were seen in 6% (95 CI 4-8), most commonly including 1) radiographic evidence of bleeding or air without an associated fixed neurological deficit, 2) cranial nerve dysfunction, and 3) delayed awakening. Permanent complications (excluding death) were seen in 1% (95% CI 0.5-2), most commonly including cranial nerve dysfunction and limb weakness. 5 deaths were reported in the entire pooled cohort of 1002 children (0.5%). Gliomas represented 92% of tumors (95% CI 89-95). Of the gliomas for which WHO grading was provided, 68% were high grade (III/IV).

CONCLUSION
When counseling families on the merits of brainstem biopsy in children, it is reasonable to state that permanent morbidity is rare (&lt; 2%). If biopsy is performed specifically to facilitate enrollment in clinical trials requiring a molecular diagnosis, the risks of biopsy outlined here should be weighed against potential benefits of trial enrollment.
DIPG-31. IS RE-IRRADIATION A POTENTIAL SURVIVAL BENEFIT FOR PATIENTS WITH DIFFUSE INTRINSIC PONTINE GLIOMA?
Authors: Dassi Natália , Torquato Ana C S , Chen Michael , Figueiredo Maria L , Rodrigues Jessica B , Cavalheiro Sergio , Dastoli Patricia A , Alves Maria T S , Silva Frederico A , Moraes Carlota V B , Silva Nasjla S , Cappellano Andrea M 
Published: June 2024

Abstract

BACKGROUND
Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma with dismal prognosis. Radiation therapy (RT) offers a transient benefit and re-irradiation (reRT) may be an option at disease progression.

OBJECTIVE
To evaluate the outcome of patients with DIPG at progression in a single institution.

METHODS
Between 2010-2023, 55 patients were evaluated, retrospectively, in respect of their treatment-one RT course versus re-RT) and concomitant medications. Overall survival (OS) was measured from diagnosis to date of death and from reRT to death using Kaplan–Meier and log-rank test.

RESULTS
Median age was 7.1 years (range 2.9-16.2y). Twenty-two patients underwent biopsy with 11 performing immunohistochemistry for H3K27M (9 mutated). In nine cases molecular analyses was evaluated: 6 H3.3K27M-mutant (2 simultaneously TP53 + 1PTPRZ1-MET fusion), 1 H3.1K27M-mutant, 1 H3C2-mutant + ACVR1 mutation and 1 PDGFRA + KIT amplifications. Thirty-five patients completed the initial course of RT (54Gy- 13-33 daily fraction), 30/35 also received valproic acid (VA), 5/35 bevacizumab, 3/35 nimotuzumab and 1/35 nivolumab+ipilimumab. Twenty patients underwent re-RT at first progression, four with 54 Gy (30x 180Gy), nine with 50Gy (25x 200Gy) and seven with median dose of 30Gy (26-39Gy), depending on their clinical status. These group also received valproic acid(8/20), bevacizumab(8/20), nivolumab(1/20) and ONC 201(1/20). Patients who received reRT showed prolonged OS compared to no reRT (median 524 vs 351 days; p=0.013). ReRT was well tolerated with 15(75%) patients experiencing stable to improved neurologic function. Patients with better clinical status and 50-54Gy reRT doses, showed prolonged OS (median 238 vs 135 days; p=0.1). Median OS from re-RT to death was 174 days (range, 14-218 days) with eight patients alive to date.

CONCLUSIONS
Re-irradiation with 50-54Gy seems safe and feasible for DIPG patients after disease progression from the first treatment, with mostly patients experiencing neurological improvement and prolonged life period.