julilili42/papers huggingface dataset:
Privileges, Wokeness, and Identity Politics
2023-09-01

The discussion of privileges is nothing new within educational science. The term ‘educational privilege’ was already used in the 1960s and 70s to point out how societal elites instrumentalised educational institutions. What is a relatively new phenomenon are the conversations in German-speaking countries about other privileges – such as masculinity, Whiteness and heterosexuality. The term of privilege is being reinterpreted in the context of emancipatory identity politics, and turned into a slogan in political debates. This opens up new possibilities for the pedagogical discourse. The essay does not only try to outline those but to point out the dangers of a conversation about privileges which is dominated by moralisation, and where the much needed social criticism is being pushed into the background.
Advancements in computational modelling of biological systems: seventh annual SysMod meeting
2023-09-01

Abstract Summary The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by awarding the three best posters. This report summarizes the key highlights and outcomes of the meeting. Availability and implementation All resources and further information are freely accessible at https://sysmod.info.
Sleep consolidates stimulus–response learning
2023-09-01

Performing a motor response to a sensory stimulus creates a memory trace whose behavioral correlates are classically investigated in terms of repetition priming effects. Such stimulus–response learning entails two types of associations that are partly independent: (1) an association between the stimulus and the motor response and (2) an association between the stimulus and the classification task in which it is encountered. Here, we tested whether sleep supports long-lasting stimulus–response learning on a task requiring participants (1) for establishing stimulus–classification associations to classify presented objects along two different dimensions (“size” and “mechanical”) and (2) as motor response (action) to respond with either the left or right index finger. Moreover, we examined whether strengthening of stimulus–classification associations is preferentially linked to nonrapid eye movement (non-REM) sleep and strengthening of stimulus–action associations to REM sleep. We tested 48 healthy volunteers in a between-subjects design comparing postlearning retention periods of nighttime sleep versus daytime wakefulness. At postretention testing, we found that sleep supports consolidation of both stimulus–action and stimulus–classification associations, as indicated by increased reaction times in “switch conditions”; that is, when, at test, the acutely instructed classification task and/or correct motor response for a given stimulus differed from that during original learning. Polysomnographic recordings revealed that both kinds of associations were correlated with non-REM spindle activity. Our results do not support the view of differential roles for non-REM and REM sleep in the consolidation of stimulus–classification and stimulus–action associations, respectively.
#142 An international randomized phase III trial comparing radical hysterectomy and pelvic node dissection (RH) vs simple hysterectomy and pelvic node dissection (SH) in patients with low-risk early-stage cervical cancer (LRESCC)
2023-09-01

<h3>Introduction/Background</h3> The objective of this non-inferiority phase III prospective randomized trial was to compare RH to SH in women with LRESCC. <h3>Methodology</h3> Women with LRESCC defined as stage IA2 or IB1 disease with lesions ≤2cm were randomized to RH or SH. The primary endpoint was pelvic recurrence rate at 3 years (PRR3). Primary intention to treat (ITT) analysis included all patients randomized. Secondary endpoints included extra-pelvic relapse-free survival (EPRFS), overall survival (OS) and patient reported outcome. <h3>Results</h3> 700 women were enrolled from December 2012 to November 2019. Median age was 44 (24-80); 91.7% were stage 1B1 and 61.7% were squamous histology. On final pathology, lymph node metastasis occurred in 3.7% (3.3% SH and 4.4% RH), positive margins in 2.5% (2.1% SH and 2.9% RH), and lesions &gt;2cm in 4.25% (4.4% SH and 4.1% RH). A total of 8.8% of women received post-surgical adjuvant therapy (9.2% SH and 8.4% RH). With a median follow-up of 4.5 years, 21 pelvic recurrences occurred (11 SH and 10 RH). The PRR3 was 2.52% with SH and 2.17% with RH (difference 0.35% with 95% upper confidence limit 2.32%) in ITT analysis. The 3-year EPRFS and OS were respectively 98.1% and 99.1% with SH; 99.7% and 99.4% with RH. SH had less bladder (9 vs 3) and ureteral injuries (5 vs 3) and significantly less urinary incontinence (4.7% vs. 11.0%; p=0.003) and urinary retention (0.6% vs. 9.9%; p&lt;0.0001) compared to RH. QoL scales with significant difference between the two groups over time were all in favor of SH. <h3>Conclusion</h3> The pelvic recurrence rate at 3 years in women with LRESCC who underwent SH was not inferior to RH and was associated with fewer surgical complications and better QoL.. SH should be considered the new standard of care. <h3>Disclosures</h3> None
Diversity-Aware Recommendations for Social Justice? Exploring User Diversity and Fairness in Recommender Systems
2023-09-01

&lt;p&gt;Diversity and fairness are increasingly linked in the field of personalized recommendations. For instance, the diversification of items (&rdquo;item diversity&rdquo;) is considered key to fairness. Less attention has been paid to &rdquo;user diversity&rdquo; and its implications for fairness. In this paper, I problematize the conceptualization and application of user diversity in recommender systems. I argue that the widespread understanding of user diversity as natural, value-neutral, and individual-level categories may accidentally compound historical injustice. To mitigate emerging biases, diversity dimensions need to be contextualized by mapping structural inequalities between users. The paper thus stresses the importance of paying attention to the structural context of diversity, whereas the context refers to political and social circumstances surrounding the user&rsquo;s life. The paper makes three contributions: 1) It connects fairness to diversity literature in the field of recommender system, 2) it specifies the tension between item-side and user-side fairness by revealing a bias in the treatment of user diversity, 3) it proposes solutions to mitigate the bias by drawing on Black feminist and critical race theory.&lt;/p&gt; &lt;p&gt;This is a draft of the accepted paper &quot;Diversity-Aware Recommendations for Social Justice? Exploring User Diversity and Fairness in Recommender Systems&quot; presented at UMAP &#39;21: Adjunct Proceedings of the 29th ACM Conference on User Modeling, Adaptation and Personalization, June 2021, Pages 404&ndash;410, https://doi.org/10.1145/3450614.3463293.&lt;/p&gt; &lt;p&gt;&nbsp;&lt;/p&gt;
Cyclotron resonant scattering feature simulations
2023-09-01

Context. Cyclotron resonant scattering features (CRSFs) are formed by scattering of X-ray photons off quantized plasma electrons in the strong magnetic field (of the order 1012 G) close to the surface of an accreting X-ray pulsar. Due to the complex scattering cross-sections, the line profiles of CRSFs cannot be described by an analytic expression. Numerical methods, such as Monte Carlo (MC) simulations of the scattering processes, are required in order to predict precise line shapes for a given physical setup, which can be compared to observations to gain information about the underlying physics in these systems. Aims. A versatile simulation code is needed for the generation of synthetic cyclotron lines. Sophisticated geometries should be investigatable by making their simulation possible for the first time. Methods. The simulation utilizes the mean free path tables described in the first paper of this series for the fast interpolation of propagation lengths. The code is parallelized to make the very time-consuming simulations possible on convenient time scales. Furthermore, it can generate responses to monoenergetic photon injections, producing Green’s functions, which can be used later to generate spectra for arbitrary continua. Results. We develop a new simulation code to generate synthetic cyclotron lines for complex scenarios, allowing for unprecedented physical interpretation of the observed data. An associated XSPEC model implementation is used to fit synthetic line profiles to NuSTAR data of Cep X-4. The code has been developed with the main goal of overcoming previous geometrical constraints in MC simulations of CRSFs. By applying this code also to more simple, classic geometries used in previous works, we furthermore address issues of code verification and cross-comparison of various models. The XSPEC model and the Green’s function tables are available online (see link in footnote, page 1).
Evidence for different accretion regimes in GRO J1008−57
2023-09-01

We present a comprehensive spectral analysis of the BeXRB GRO J1008−57 over a luminosity range of three orders of magnitude using NuSTAR, Suzaku, and RXTE data. We find significant evolution of the spectral parameters with luminosity. In particular, the photon index hardens with increasing luminosity at intermediate luminosities in the range 1036–1037 erg s−1. This evolution is stable and repeatedly observed over different outbursts. However, at the extreme ends of the observed luminosity range, we find that the correlation breaks down, with a significance level of at least 3.7σ. We conclude that these changes indicate transitions to different accretion regimes, which are characterized by different deceleration processes, such as Coulomb or radiation breaking. We compare our observed luminosity levels of these transitions to theoretical predications and discuss the variation of those theoretical luminosity values with fundamental neutron star parameters. Finally, we present detailed spectroscopy of the unique “triple peaked” outburst in 2014/15 which does not fit in the general parameter evolution with luminosity. The pulse profile on the other hand is consistent with what is expected at this luminosity level, arguing against a change in accretion geometry. In summary, GRO J1008−57 is an ideal target to study different accretion regimes due to the well-constrained evolution of its broad-band spectral continuum over several orders of magnitude in luminosity.
Cluster Analysis To Explore Clinical Subphenotypes Of Eosinophilic Granulomatosis With Polyangiitis (Churg–Strauss)
2023-09-01

Objective Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA) could be determined by presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. Methods This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal, mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central or peripheral neurological involvement); a second model also included ANCA results. Results The analyses included 489 patients diagnosed in 1984–2015. ANCA were detected in 37.2% of patients, mostly P-ANCA (85.4%) and/or anti-myeloperoxidase (87.0%). Compared with ANCA-negative patients, those with ANCA had more renal (P&lt;0.001) and peripheral neurological involvement (P=0.04), fewer cardiovascular signs (P&lt;0.001) and fewer biopsies with eosinophilic tissue infiltrates (P=0.001). The cluster analyses generated four (model without ANCA) and five clusters (model with ANCA). Both models identified three identical clusters of 34, 39 and 40 patients according to the presence or absence of ENT, CNS and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. Conclusion Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and –negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.
P19.08.B INCREASED CORTICAL EXCITABILITY TO TRANSCRANIAL MAGNETIC STIMULATION CONTRIBUTE TO EPILEPTOGENESIS IN IDH1-MUTANT GLIOMAS
2023-09-01

Abstract BACKGROUND In-vitro studies indicate that gliomas with a mutation of the isocitrate dehydrogenase (IDH) increase neuronal excitability of the peritumoral cortex contributing to epileptogenesis in these patients. However, in-vivo evidence is missing. This study evaluates the electric characteristics of the brain-tumor-interface (BTI) relative to the IDH mutation status. MATERIAL AND METHODS To investigate peritumoral cortical excitability (CE), we applied 5258 pulses of transcranial magnetic stimulation (TMS) at the BTI of IDH-mutant (IDH-mt) and IDH-wildtype (IDH-wt) glial tumors in 39 patients. CE was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (i.e., event-related spectral perturbation, ERSP) after TMS. ERSP values were related to the IDH status, tumor grading, antiepileptic drug intake (AED) and the spatial relationship to the tumor borders. RESULTS There was not significant group difference in RMT. TMS to the BTI triggered an EMG synchronization decreasing linearly with the distance to the functional hotspot. In contrast, IDH-mt gliomas demonstrated an increased cortical output of the peritumoral brain tissue compared to IDH-wt gliomas. This effect was not attributable to AED intake or other histological and molecular characteristics. Notably, cortical hyperexcitability was detectable well beyond the tumor border. CONCLUSION s: This study provides in-vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas which could contribute to the epileptogenesis in these patients.
PL01.4.A LATE BREAKING ABSTRACT: A LONG PEPTIDE VACCINE TARGETING THE CLONAL DRIVER MUTATION H3K27M IN ADULT PATIENTS WITH DIFFUSE MIDLINE GLIOMA
2023-09-01

Abstract BACKGROUND Clonal and mutually exclusive substitution of lysine 27 to methionine in histone H3-3A (H3K27M) defines an aggressive subtype of diffuse glioma. These diffuse midline gliomas (DMG) are aggressive, incurable primary brain tumors that occur predominantly in a midline location in children and young adults. Surgical treatment options remain limited, response to chemoradiation is poor and palliative radiotherapy remains the only intervention with proven benefit, resulting in a median overall survival between 10 and 15 months after initial diagnosis. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses capable of controlling H3K27M+ tumors in a major histocompatibility complex (MHC)-humanized mouse model. MATERIAL AND METHODS Here we describe the first-in-human treatment with H3K27M-vac of eight adult patients with recurrent H3K27M+ DMG. Induction of mutation-specific immune responses was determined in peripheral blood using Interferon-γ ELISpot assays. Class II HLA-restricted peripheral H3K27M-specific T cells were expanded in vitro to characterize and track unique H3K27M-reactive T cell responses in blood and cerebrospinal fluid (CSF). RESULTS Repeat vaccinations with H3K27M-vac were safe and induced mutation-specific immune responses in five of eight patients after a median of two vaccinations. Median progression free survival after start of vaccination was 6.2 months and median overall survival was 12.8 months. In vitro restimulation of peripheral CD4+ and CD8+ T cells with H3 mutant peptide or wild type peptide revealed that H3K27M specific immune responses are CD4-mediated and can be suppressed by blocking antibodies against MHC II, but not MHC I. Furthermore, proximity ligation assay of formalin-fixed paraffin-embedded primary tumor tissue revealed that H3K27M neoepitope co-localizes with HLA class II-DR. One patient showed radiographic pseudoprogression (PsPD) according to iRANO criteria within six weeks after first detection of mutation-specific peripheral immune response. Following PsPD, three out of the top ten vaccine-induced, K27M-expanded CD4+ TCR clonotypes from peripheral blood were detectable in the CSF of this patient who went into sustained complete remission for &amp;gt; 31 months. CONCLUSION H3K27M-vac is safe and induces H3K27M-specific CD4 T cell responses in patients with H3K27M+ DMG. An ongoing multicenter, phase 1 clinical trial for adult patients with newly diagnosed H3K27M+ DMG will assess the safety and immunogenicity of H3K27M-vac in combination with atezolizumab in standard-of-care radiotherapy (NCT04808245).
P08.03.A CAREGIVERS OF ADULT NEURO-ONCOLOGICAL PATIENTS: UNMET NEEDS AND RELEVANT PROBLEMS - A PROSPECTIVE STUDY
2023-09-01

Abstract BACKGROUND The diagnosis of a brain tumor represents high burden for patients’ caregivers. Psychosocial screening tools for caregivers adapted to neuro-oncological tumor entities are urgently required but do not exist. To bridge this gap, we aim to develop a problem list in terms of a holistic need assessment tailored to their unmet needs of caregivers for an application in combination to the NCCN distress thermometer scale. MATERIAL AND METHODS First, items of high relevance for the caregivers were identified on basis of retrospective analyses. Second, we prospectively conducted an assessment in two centers: in the first center, caregivers filled out a questionnaire (center A), in the second center, the questionnaire was applied as qualitative interview with caregivers (center B). We performed a qualitative content analysis applying inductive/deductive categorizations of the reports. RESULTS The qualitative interviews included n=11 main questions and up to 4 subquestions focusing on changes in everyday life, relationship, social live, emotional, physical, financial, spiritual problems and support needs. A total of 47 caregivers were assessed (n=25 in center A via questionnaire, n=22 in center B via interviews) during outpatient visits. Most of the caregivers wished for psychological support (27/47, 57%), first contact with psycho-oncologists after first diagnosis (25/47, 53%) or in case of a clinical deterioration (28/47, 59%). Strategies for problem solving (26/47, 55%) and finding sources of strength (22/47, 47%) were most important regarding needed support. Changes in everyday life’ were reported by 87% of caregivers (41/47), including constraints/organization of (medical) appointments (24/47, 51%) or constant availability required for the partner (20/47, 43%). Also, 70% (33/47) put their own interests last or adapt their leisure activities. In the qualitative interviews (Center B), additional items indicating caregiver burden were identified: “dealing with psychological problems of the patient” (3/22, 16%), “different coping strategies among patient and caregiver” (4/22, 18%). Emotional problems, particularly depressive symptoms were addressed more profoundly in the qualitative interviews (“loss of interest and feelings of sadness”, 4/22, 18%). CONCLUSION The interviews reflected the unmet needs of brain tumor caregivers and allow for the targeted assessment of the specific burdens. Furthermore, we were able to gather more in-depth information per qualitative interviews.
P13.04.A REPRODUCIBLE CRISPR-SEQ PIPELINE FOR NGS FUNCTIONAL GENOMICS SCREENINGS FOR GLIOMA CELL LINES
2023-09-01

Abstract BACKGROUND The CRISPR/Cas9 genome editing technology has revolutionized the field of functional genomics by enabling precise editing of DNA. Over the past few years, CRISPR technology has been widely employed to identify genetic dependencies in a broad spectrum of applications paving the way for the discovery and validation of relevant molecular targets, for example potential drug targetsGlioblastoma are incurable primary tumors of the central nervous system. Functional genomics could enable the discovery of novel therapeutic targets or even combination therapies. MATERIAL AND METHODS Here, we present a bioinformatics pipeline that combines functional screens and target editing analysis to identify potential vulnerabilities and drug targets in glioblastoma or other diseases. The pipeline consists of two workflows, one performing functional screening and one performing base editing analysis. This developed CRISPR-seq pipeline is reproducible and containerized, allowing high-throughput processing. All processes are modularized in Nextflow DSL2 (Domain Specific Language) and versioned which facilitates maintainability and customization, as well as the addition of new tools. A quality control report is also automatically generated, allowing the user an overview of their ran experiments. The pipeline also helps us to keep the data FAIR (Findable, Accessible, Interoperable and Reusable) and optimized, making it easier to share with other researchers and collaborate on future studies. RESULTS This pipeline was applied to functional screens using CRISPR/Cas9 genome-wide knockout or activation libraries to detect genetic vulnerabilities that might enhance drug treatment efficacy, e.g. for ataxia telangiectasia and Rad3 related (ATR) inhibition in experimental glioma.With this pipeline, we were able to identify several genes that are involved in drug resistance in glioblastoma, by starting from raw data (fastq files) to genes presenting vulnerabilities.The results obtained through our pipeline provided important information on the disease's molecular mechanisms, which were subsequently confirmed through wet lab validation. CONCLUSION In conclusion, the crisprseq software described in this abstract is a powerful tool for identifying potential genetic dependencies. The pipeline aims at analyzing this output data in a reproducible and containerized way using Nextflow and respecting nf-core community standards. By combining functional screens and base editing analysis with bioinformatics tools, this pipeline allows for the identification of essential genes and pathways, as well as the characterization of specific mutations that contribute to the development and progression of glioblastoma.