julilili42/papers huggingface dataset:
In-depth analysis of serum antibodies against Epstein-Barr virus lifecycle proteins, and EBNA1, ANO2, GlialCAM and CRYAB peptides in patients with multiple sclerosis
2024-12-17

Background A strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment. Methods In this retrospective cross-sectional study, 258 serum samples were included consisting of EBV-negative (n = 25) and EBV-positive (n = 36) controls, 192 MS samples including untreated relapsing-remitting MS (RRMS) with and without relapses, secondary progressive MS (SPMS) and primary progressive MS (PPMS) patients, and 106 patients on 8 different treatment regimens. IgG and IgM antibody titers against EBV docking/fusion proteins (gp350, gh/gp42, gh/gL/gp42), immediate early antigen (BZLF1), early antigens (EA p85, EA P138, EA P54), capsid antigens (VCA P18, VCA P23, VCA gp125) and late antigens (EBNA1) were measured. Specific EBNA1 and GlialCAM, CRYAB and ANO2 peptides were synthesized and also incorporated in our custom magnetic bead based multiplex assay. Results We observed significantly elevated IgG antibody titers in EBV-positive controls, RRMS with and without relapse, SPMS and PPMS patients for all lifecycle antigens except for several early antigens when compared to EBV-negative controls. Significantly higher IgG antibody titers were observed in RRMS patients for fusion proteins and EBNA1 peptides when compared to EBV-positive controls. An MS specific response was observed for ANO2 but not for GlialCAM or CRYAB. No significant treatment effects or a specific IgM response were detectable. Conclusion The MS-specific, differential antibody response to EBV antigens confirms an altered immunological response to EBV in MS patients. EBV reactivation does not appear to play an important role in MS pathogenesis and no differential antibody signatures were observed between MS disease phases. The MS-specific anti-ANO2 antibody response suggests a potential role for EBNA1 as an antigenic driver, although the exact role of anti-ANO2 antibodies needs to be determined. The precise pathophysiological role of EBV in MS remains uncertain and requires further investigation.
Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer’s disease
2024-12-17

Abstract Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer’s disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies. Using a sample of individuals with amnestic mild cognitive impairment and probable mild Alzheimer’s disease dementia from the German Center for Neurodegenerative Diseases (DZNE)-Longitudinal Cognitive Impairment and Dementia (DELCODE) study cohort (N = 309, aged 67–96 years, 51% female), we assessed cross-sectional relationships between a latent factor representing the functional integrity of an affect-related executive regulation network and agitation point prevalence and severity scores. In a subsample of individuals with locus coeruleus MRI imaging data (N = 37, aged 68–93 years, 49% female), we also investigated preliminary associations between locus coeruleus MRI contrast ratios (a measure of structural integrity, whole or divided into rostral, middle, and caudal thirds) and individual affect-related regulation network factor scores and agitation measures. Regression models controlled for effects of age and clinical disease severity and, for models including resting-state functional MRI connectivity variables, grey matter volume and education years. Agitation point prevalence showed a positive relationship with a latent factor representing the functional integrity (and a negative relationship with a corresponding structural measure) of the affect-related executive regulation network. Locus coeruleus MRI contrast ratios were positively associated with agitation severity (but only for the rostral third, in N = 13) and negatively associated with the functional affect-related executive regulation latent factor scores. Resting-state functional connectivity between a medial prefrontal cortex region and the left amygdala was related to locus coeruleus MRI contrast ratios. These findings implicate the involvement of locus coeruleus integrity and emotion dysregulation in agitation in Alzheimer’s disease and support the presence of potential compensatory processes. At the neural level, there may be a dissociation between mechanisms underlying agitation risk per se and symptom severity. Further studies are needed to replicate and extend these findings, incorporating longitudinal designs, measures of autonomic function and non-linear modelling approaches to explore potential causal and context-dependent relationships across Alzheimer’s disease stages.
Quantum computing topological invariants of two-dimensional quantum matter
2024-12-17

Quantum algorithms provide a potential strategy for solving computational problems that are intractable by classical means. Computing the topological invariants of topological matter is one central problem in research on quantum materials, and a variety of numerical approaches for this purpose have been developed. However, the complexity of quantum many-body Hamiltonians makes calculations of topological invariants challenging for interacting systems. Here, we present two quantum circuits for calculating Chern numbers of two-dimensional quantum matter on quantum computers. Both circuits combine a gate-based adiabatic time evolution over the discretized Brillouin zone with particular phase estimation techniques. The first algorithm uses many qubits, and we analyze it using a tensor-network simulator of quantum circuits. The second circuit uses fewer qubits, and we implement it experimentally on a quantum computer based on superconducting qubits. Our results establish a method for computing topological invariants with quantum circuits, taking a step towards characterizing interacting topological quantum matter using quantum computers. Published by the American Physical Society 2024
Who is We: Capturing Social Identity Content by Integrating Qualitative Methods in Survey-Based Approaches
2024-12-17

The concept of social identity presents a significant challenge when attempting to capture the multifaceted meanings associated with it. A pertinent example of this complexity can be observed in the investigation of the underlying significance of European identity. Past quantitative research on social identity has largely focused on the extent to which individuals identify with Europe, and only in a limited way on the meaning and content of that identity. This is problematic because depending on the content of European identity, it may be associated with varying positions toward issues like immigration or Euroscepticism. In this methodological article, we compare strengths and limitations of two existing yet under-utilized methods that can be used to assess social identity content and that can be implemented in survey research. These represent open-ended questions on what it means to be European and Q methodology, asking participants to sort different aspects of Europe according to whether they strengthen or weaken attachment. Different analytical methods exist to group participants’ answers, leading to different results. We compare these approaches by drawing on four studies (total N = 1,932; adolescents, young adults, and adult samples) from Germany.
Advancements in Laparoscopic Techniques for Perineal Hernias—Technical Success and Complications Data
2024-12-17

Purpose: Multimodal approaches, including radiochemotherapy and surgical resection, are commonly used to treat rectal malignancies. Postoperative perineal hernias, though not uncommon, have shown an increasing incidence in recent years. Managing symptomatic perineal hernias presents a challenge, with a high recurrence rate after repair. This retrospective study investigates the laparoscopic placement of a non-absorbable mesh for treating pelvic floor hernias involving bowel displacement. Methods: This study included all consecutive patients requiring hernia repair due to symptomatic perineal hernias following minimally invasive abdominoperineal resection. All patients had a history of local radiation therapy. Data were collected on surgery duration, intra- and postoperative complications, and hernia recurrence rates. Results: Laparoscopic displacement of the small bowel from the pelvis was performed on eight patients, and closure of the pelvic floor hernia area was achieved using non-absorbable mesh placement. All procedures were successful, and no perioperative complications were recorded. Only one early complication occurred, classified as Clavien-Dindo II. Conclusions: The laparoscopic procedure, serving as a safe method for repositioning the small intestine and closing a perineal hernia using a mesh, has shown promising outcomes. The use of a non-absorbable mesh as an alternative to native tissue appears to be effective, with no observed recurrent hernias. However, further evaluation through long-term results or a larger cohort study is still pending.
Development and validation of a molecular classifier of meningiomas
2024-12-18

Abstract Background Meningiomas exhibit considerable clinical and biological heterogeneity. We previously identified 4 distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, and proliferative) that address much of this heterogeneity. Despite the utility of these groups, the stochasticity of clustering methods and the use of multi-omics data for discovery limits the potential for classifying prospective cases. We sought to address this with a dedicated classifier. Methods Using an international cohort of 1698 meningiomas, we constructed and rigorously validated a machine learning-based molecular classifier using only DNA methylation data as input. Original and newly predicted molecular groups were compared using DNA methylation, RNA sequencing, copy number profiles, whole-exome sequencing, and clinical outcomes. Results We show that group-specific outcomes in the validation cohort are nearly identical to those originally described, with median progression-free survival (PFS) of 7.4 (4.9–Inf) years in hypermetabolic tumors and 2.5 (2.3–5.3) years in proliferative tumors (not reached in the other groups). Tumors classified as NF2-wildtype had no NF2 mutations, and 51.4% had canonical mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group, and cell cycle programs in the proliferative group. Bulk deconvolution similarly revealed the enrichment of macrophages in immunogenic tumors and neoplastic cells in hypermetabolic and proliferative tumors with similar proportions to those originally described. Conclusions Our DNA methylation-based classifier, which is publicly available for immediate clinical use, recapitulates the biology and outcomes of the original molecular groups as assessed using multiple metrics/platforms that were not used in its training.
Macrovascular contributions to resting-state fMRI signals: A comparison between EPI and bSSFP at 9.4 Tesla
2024-12-18

Abstract The draining-vein bias of T2*-weighted sequences, like gradient echo echo-planar imaging (GRE-EPI), can limit the spatial specificity of functional MRI (fMRI). The underlying extravascular signal changes increase with field strength (B0) and the perpendicularity of draining veins to the main axis of B0, and are, therefore, particularly problematic at ultra-high field (UHF). In contrast, simulations showed that T2-weighted sequences are less affected by the draining-vein bias, depending on the amount of rephasing of extravascular signal. As large pial veins on the cortical surface follow the cortical folding tightly, their orientation can be approximated by the cortical orientation to B0→. In our work, we compare the influence of the cortical orientation to B0→ on the resting-state fMRI signal of three sequences aiming to understand their macrovascular contribution. While 2D GRE-EPI and 3D GRE-EPI (both T2*-weighted) showed a high dependence on the cortical orientation to B0→, especially on the cortical surface, this was not the case for 3D balanced steady-state free precession (bSSFP) (T2/T1-weighted). Here, a slight increase of orientation dependence was shown in depths closest to white matter (WM). And while orientation dependence decreased with increased distance to the veins for both EPI sequences, no change in orientation dependence was observed in bSSFP. This indicates the low macrovascular contribution to the bSSFP signal, making it a promising sequence for layer fMRI at UHF.
Integrating Biological Early Warning Systems with High-Resolution Online Chemical Monitoring in Wastewater Treatment Plants
2024-12-18

Detection of micropollutants (MPs) in wastewater effluents using traditional toxicity tests or chemical analysis with discrete samples is challenging due to concentration dynamics. This study evaluates a continuous monitoring approach for detecting MPs in wastewater effluents using a combination of biological early warning systems (BEWS). Three BEWS with <i>Chlorella vulgaris</i>, <i>Daphnia magna</i>, and <i>Gammarus pulex</i> were operated in parallel in a full-scale municipal wastewater treatment plant. Concentrations of MPs were monitored by simultaneous online chemical analysis using high performance liquid chromatography-high resolution mass spectrometry (MS2Field). Over 5 weeks, behavioral changes observed in the BEWS occasionally exceeded acute toxicity thresholds, triggering alarms. These changes were related to MPs identified by the MS2Field, to abiotic factors, or to operational parameters of the BEWS. For one toxic event, behavioral responses were linked to a pesticide, not authorized in Switzerland, at concentrations close to literature EC<sub>50</sub> values. Verification tests confirmed that the pesticide in the effluent was the most likely cause for the organism response. The study demonstrates the potential of BEWS as a stand-alone technique for detecting contamination peaks in wastewater, and identifies key limitations and critical factors that need to be addressed to optimize the use of BEWS in wastewater monitoring.
Resolving Small and Mid-sized Banks: Resolution Versus Liquidation and the Transfer Tools
2024-12-18

Abstract As part of a broader reform agenda, the European Commission’s proposals for a comprehensive reform of the European Crisis Management and Deposit Insurance (CMDI) framework include a recalibration of the conditions for the initiation of resolution actions with a view to expanding the scope of resolution actions to smaller and medium-sized banking institutions. The core element in this regard is a new definition of the so-called public interest assessment (PIA), whereby the initiation of resolution actions is permissible only if resolution is ‘in the public interest’. Under the original BRRD/SRMR regime, this test required that the objectives of resolution could not equally be accomplished through the winding up of the relevant bank under traditional liquidation regimes. With a new wording, both the European Commission and the European Parliament have proposed to lower that threshold, moving towards the application of resolution procedures as the standard approach to dealing with failures also in this market segment. The present article undertakes a critical analysis of these proposals and their potential implications in the light of the rationale of the original PIA criteria and a functional comparison between resolution and liquidation.
Heterotopic ossification following severe radial head fractures: Clinical outcome and associated factors
2024-12-18

Over 50% surgically treated radial head fractures classified as Mason-Johnston types 3 and 4 developed HO, while more severe injuries led to a higher prevalence of HO. No increased rates of HO were determined for delayed surgery, surgical treatment methods, and use of HO prophylaxis. Therefore, regular HO prophylaxis might not be needed. Additionally, no significant differences in functional scores and quality of life were detected between patients with and without HO.
Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology–Guidelines 2024: imaging immediately after neoadjuvant therapy in soft tissue sarcoma, soft tissue tumor surveillance, and the role of interventional radiology
2024-12-18

Abstract Objectives An update of the first European Society of Musculoskeletal Radiology (ESSR) consensus on soft tissue tumor imaging in 2015 became necessary due to technical advancements, further insights into specific entities, and the revised WHO classification (2020) and AJCC staging system (2017). The third part of the revised guidelines covers algorithms and techniques beyond initial imaging: (1) Imaging after neoadjuvant therapy in soft tissue sarcoma, (2) sarcoma surveillance, and (3) special aspects, including surveillance of non-malignant entities and the role of interventional radiology. Materials and methods A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by level of agreement (0 to 10) during two iterative rounds that could result in either ‘group consensus,’ ‘group agreement,’ or ‘lack of agreement.’ Results The three sections contain 47 statements with comments. Group consensus was reached in 91.5%, group agreement in 6.4%, lack of agreement in 2.1%. In sarcoma, imaging immediately after neoadjuvant therapy is pivotal for determining the therapy effects and for resection-planning; surveillance should include imaging at fixed grade- and type-dependent intervals. In general, MRI is the method of choice for loco-regional surveillance of soft tissue sarcomas, and chest CT to assess metastatic disease. Interventional radiology has a role, especially in oligometastatic disease, palliative tumor control and local recurrences. Conclusion Strategies for standardized soft tissue tumor imaging regarding therapy control, surveillance, and useful interventional procedures are provided. Key Points Question An ESSR consensus update on soft tissue tumor imaging regarding surveillance became necessary due to technical advancements, further entity-specific insights, and revised WHO- and AJCC-classifications. Findings Imaging immediately after neoadjuvant therapy in soft tissue sarcoma is pivotal. Post-therapeutic surveillance should include imaging at regular intervals, stratified for tumor grade and type. Clinical relevance The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability, both in individual patients and in future studies on individualized strategies.
DreamOn: a data augmentation strategy to narrow the robustness gap between expert radiologists and deep learning classifiers
2024-12-19

Purpose Successful performance of deep learning models for medical image analysis is highly dependent on the quality of the images being analysed. Factors like differences in imaging equipment and calibration, as well as patient-specific factors such as movements or biological variability (e.g., tissue density), lead to a large variability in the quality of obtained medical images. Consequently, robustness against the presence of noise is a crucial factor for the application of deep learning models in clinical contexts. Materials and methods We evaluate the effect of various data augmentation strategies on the robustness of a ResNet-18 trained to classify breast ultrasound images and benchmark the performance against trained human radiologists. Additionally, we introduce DreamOn , a novel, biologically inspired data augmentation strategy for medical image analysis. DreamOn is based on a conditional generative adversarial network (GAN) to generate REM-dream-inspired interpolations of training images. Results We find that while available data augmentation approaches substantially improve robustness compared to models trained without any data augmentation, radiologists outperform models on noisy images. Using DreamOn data augmentation, we obtain a substantial improvement in robustness in the high noise regime. Conclusions We show that REM-dream-inspired conditional GAN-based data augmentation is a promising approach to improving deep learning model robustness against noise perturbations in medical imaging. Additionally, we highlight a gap in robustness between deep learning models and human experts, emphasizing the imperative for ongoing developments in AI to match human diagnostic expertise.
Towards Novel Antiplasmodial Agents—Design, Synthesis and Antimalarial Activity of Second-Generation β-Carboline/Chloroquine Hybrids
2024-12-19

As the resistance of Plasmodium to the existing antimalarials increases, there is a crucial need to expand the antimalarial drug pipeline. We recently identified potent antimalarial compounds, namely harmiquins, hybrids derived from the β-carboline alkaloid harmine and 4-amino-7-chloroquinoline, a key structural motif of chloroquine (CQ). To further explore the structure−activity relationship, we synthesised 13 novel hybrid compounds at the position N-9 of the β-carboline ring and evaluated their efficacy in vitro against Plasmodium falciparum 3D7 and Dd2 strains (CQ sensitive and multi-drug resistant, respectively). All compounds exhibit persistent antimalarial activity against both strains of P. falciparum. The most interesting derivatives had low nanomolar activity against both strains (IC50 (33) = 4.7 ± 1.3 nM against Pf3D7 and 6.5 ± 2.5 nM against PfDd2; IC50 (37) = 4.6 ± 0.6 nM against 3D7 and 10.5 ± 0.4 nM against Dd2). Resistance indices (RIs) ranged from 0.9 to 5.3 compared to CQ (RI = 14.4), highlighting their superior consistency in activity against both strains. The cytotoxicity screening performed on HepG2 revealed over 3 orders of magnitude higher IC50 for most of the compounds, with SIs from 711.0 to 8081.8. Spectroscopic studies explored the affinities of newly synthesised compounds for DNA, RNA, and HSA. Both tested hybrids, 34 and 39, were intrinsically fluorescent in an aqueous medium, characterised by remarkable Stokes shifts of emission maxima (Δλ = +103 and +93 nm for 34 and 39, respectively). Fluorimetric experiments revealed that compound 34, with its shorter and more flexible linker, exhibited at least an order of magnitude higher affinity toward ds-DNAs versus ds-RNA and two orders of magnitude higher affinity toward GC-DNAs compared to 39. The behaviour of the investigated compounds upon binding to HSA is very similar, showing a strong hypsochromic shift of the emission maximum (almost Δλ = −70 nm) and demonstrating their effectiveness as fluorimetric probes for distinguishing between DNA/RNA and proteins.