julilili42/papers huggingface dataset:
The German research consortium for the study of bipolar disorder (BipoLife): a quality assurance protocol for MR neuroimaging data
2024-09-26

Abstract Background The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium. Methods The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines. Discussion The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.
Stochastic Thermodynamics at the Quantum-Classical Boundary: A Self-Consistent Framework Based on Adiabatic-Response Theory
2024-09-26

Microscopic thermal machines promise to play an important role in future quantum technologies. Making such devices widely applicable will require effective strategies to channel their output into easily accessible storage systems like classical degrees of freedom. Here, we develop a self-consistent theoretical framework that makes it possible to model such quantum-classical hybrid devices in a thermodynamically consistent manner. Our approach is based on the assumption that the quantum part of the device is subject to strong decoherence and dissipation induced by a thermal reservoir. Due to the ensuing separation of time scales between slowly evolving classical and fast relaxing quantum degrees of freedom, the dynamics of the hybrid system can be described by means of adiabatic-response theory. We show that, upon including fluctuations in a minimally consistent way, the resulting equations of motion can be equipped with a first and second law, both on the ensemble level and on the level of individual trajectories of the classical part of the system, where thermodynamic quantities like heat and work become stochastic variables. As an application of our theory, we work out a physically transparent model of a quantum-classical hybrid engine, whose working system consists of a chain of Rydberg atoms, which is confined in an optical cavity and driven by periodic temperature variations. We demonstrate through numerical simulations that the engine can sustain periodic oscillations of a movable mirror, which acts as a classical load, against external friction and extract the full distributions of input heat and output work. By making the statistics of thermodynamic processes in quantum-classical hybrid systems accessible without the need to further specify a measurement protocol, our work contributes to bridging the long-standing gap between classical and quantum stochastic thermodynamics.
Towards the definition of a standard in TMS-EEG data preprocessing
2024-09-27

Combining Non-Invasive Brain Stimulation (NIBS) techniques with the recording of brain electrophysiological activity is an increasingly widespread approach in neuroscience. Particularly successful has been the simultaneous combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Unfortunately, the strong magnetic pulse required to effectively interact with brain activity inevitably induces artifacts in the concurrent EEG acquisition. Therefore, a careful but aggressive pre-processing is required to efficiently remove artifacts. Unfortunately, as already reported in the literature, different preprocessing approaches can introduce variability in the results. Here we aim at characterizing the three main TMS-EEG preprocessing pipelines currently available, namely ARTIST (Wu et al., 2018), TESA (Rogasch et al., 2017) and SOUND/SSP-SIR (Mutanen et al., 2018, 2016), providing an insight to researchers who need to choose between different approaches. Differently from previous works, we tested the pipelines using a synthetic TMS-EEG signal with a known ground-truth (the artifacts-free to-be-reconstructed signal). In this way, it was possible to assess the reliability of each pipeline precisely and quantitatively, providing a more robust reference for future research. In summary, we found that all pipelines performed well, but with differences in terms of the spatio-temporal precision of the ground-truth reconstruction. Crucially, the three pipelines impacted differently on the inter-trial variability, with ARTIST introducing inter-trial variability not already intrinsic to the ground-truth signal.
Phenotype-driven genomics enhance diagnosis in children with unresolved neuromuscular diseases
2024-09-27

Establishing a molecular diagnosis remains challenging in half of individuals with childhood-onset neuromuscular diseases (NMDs) despite exome sequencing. This study evaluates the diagnostic utility of combining genomic approaches in undiagnosed NMD patients. We performed deep phenotyping of 58 individuals with unsolved childhood-onset NMDs that have previously undergone inconclusive exome studies. Genomic approaches included trio genome sequencing and RNASeq. Genetic diagnoses were reached in 23 out of 58 individuals (40%). Twenty-one individuals carried causal single nucleotide variants (SNVs) or small insertions and deletions, while 2 carried pathogenic structural variants (SVs). Genomic sequencing identified pathogenic variants in coding regions or at the splice site in 17 out of 21 resolved cases, while RNA sequencing was additionally required for the diagnosis of 4 cases. Reasons for previous diagnostic failures included low coverage in exonic regions harboring the second pathogenic variant and involvement of genes that were not yet linked to human diseases at the time of the first NGS analysis. In summary, our systematic genetic analysis, integrating deep phenotyping, trio genome sequencing and RNASeq, proved effective in diagnosing unsolved childhood-onset NMDs. This approach holds promise for similar cohorts, offering potential improvements in diagnostic rates and clinical management of individuals with NMDs.
The EU’s Approach to Sanctions on Russia: A Critical Analysis of the Existing Literature
2024-09-27

This article focuses on the EU's sanctions against Russia, which were adopted in several rounds after Russia’s aggressive actions against Ukraine in 2014 and 2022. This article reviews and critically examines the existing academic works on this topic. In particular, it identifies, distinguishes and analyses five types of the existing scholarship, each of which relies on a different explanatory perspective on why the EU has adopted its sanctions against Russia. These are: (1) convergence of normative views within the EU, (2) national preference-based bargaining, (3) emotional resonance and (dis)trust in relation to the Russia-Ukraine conflict, (4) the EU’s ambition to be an active political-security actor and (5) threat perception of the EU’s geographical proximity with Ukraine. Additionally, the article reviews the debates on the (in)effectiveness of the EU’s sanctions on Russia. Although the extant literature offers different perspectives and has been expanding, there are still some gaps in the existing scholarship, which are also discussed in the article.
Novel 3-dimensional effective regurgitation orifice area quantification serves as a reliable tool to identify severe mitral valve regurgitation
2024-09-27

Abstract A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly ( p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly ( r = 0.501, p &lt; 0.001) better with the pre-defined MR severity. We detected crucial differences in the correct identification of severe MR between 2D and 3D techniques, thus 2D PISA significantly ( p &lt; 0.0001) underestimates EROA due to clinical and morphological parameters. The assessment of 3D VCA resulted in improved diagnostic accuracy.
Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon
2024-09-27

The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes. Through pathway analysis of the thousands of phosphopeptides identified, we reveal "membrane trafficking" as a dominant signature with the vesicle trafficking protein SEC22 Homolog B (SEC22B) S137 phosphorylation being a top hit. Hepatocyte-specific loss- and gain-of-function experiments reveal that SEC22B was a key regulator of glycogen, lipid and amino acid metabolism, with SEC22B-S137 phosphorylation playing a major role in glucagon action. Mechanistically, we identify several protein binding partners of SEC22B affected by glucagon, some of which were differentially enriched with SEC22B-S137 phosphorylation. In summary, we demonstrate that phosphorylation of SEC22B is a hepatocellular signaling node mediating the metabolic actions of glucagon and provide a rich resource for future investigations on the biology of glucagon action.
A conserved cell-pole determinant organizes proper polar flagellum formation
2024-09-27

Abstract The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.
Has Ghana's Rotavirus Vaccine Switch Met Programmatic Expectations? An Analysis of National Surveillance Data; 2018–2022
2024-09-27

Abstract Background Ghana introduced a 2-dose schedule rotavirus vaccine, Rotarix, into childhood immunization in 2012 but switched to a 3-dose schedule vaccine, Rotavac, in 2020 on account of programmatic advantages offered by the latter, including lower cost per fully immunized child and lower cold chain volume requirement. The objective of the study was to assess the effect of the vaccine switch on the trends of rotavirus vaccine uptake and health facility outpatient department (OPD) attendance due to diarrhea among children aged 1–11 months. Methods A retrospective analysis was conducted on childhood immunization and diarrhea surveillance data for 2018–2022. The uptake of the different rotavirus vaccine products and the proportion of health facility OPD attendance attributed to diarrhea, respectively, were compared between the pre- and postswitch study periods. Results The uptake of rotavirus vaccine was sustained following the switch. There were no significant differences in vaccination coverages (rota1, Rotarix coverage [94.3%], vs rota1, Rotavac coverage [95.3%]; P = .757; rota2, Rotarix coverage [91.3%], vs rota2, Rotavac coverage [92.7%]; P = .789). The proportions of health facility OPD attendance due to diarrhea were comparable (preswitch [12.4%] vs postswitch [12.1%]; P = .838). Conclusions Ghana's rotavirus vaccine switch yielded expected programmatic benefits without any untoward effects. The trends of vaccine uptake and reduction in diarrhea morbidity were sustained. These experiences and lessons from the rotavirus vaccine switch are vital for potential switches for other vaccines in the current immunization schedule to mitigate the annual vaccine expenditure.
The Plastidial Protein Acetyltransferase GNAT1 Forms a Complex With GNAT2, yet Their Interaction Is Dispensable for State Transitions
2024-09-28

Protein N-acetylation is one of the most abundant co- and post-translational modifications in eukaryotes, extending its occurrence to chloroplasts within vascular plants. Recently, a novel plastidial enzyme family comprising eight acetyltransferases that exhibit dual lysine and N-terminus acetylation activities was unveiled in Arabidopsis. Among these, GNAT1, GNAT2, and GNAT3 reveal notable phylogenetic proximity, forming a subgroup termed NAA90. Our study focused on characterizing GNAT1, closely related to the state transition acetyltransferase GNAT2. In contrast to GNAT2, GNAT1 did not prove essential for state transitions and displayed no discernible phenotypic difference compared to the wild type under high light conditions, while gnat2 mutants were severely affected. However, gnat1 mutants exhibited a tighter packing of the thylakoid membranes akin to gnat2 mutants. In vitro studies with recombinant GNAT1 demonstrated robust N-terminus acetylation activity on synthetic substrate peptides. This activity was confirmed in vivo through N-terminal acetylome profiling in two independent gnat1 knockout lines. This attributed several acetylation sites on plastidial proteins to GNAT1, reflecting a subset of GNAT2’s substrate spectrum. Moreover, co-immunoprecipitation coupled with mass spectrometry revealed a robust interaction between GNAT1 and GNAT2, as well as a significant association of GNAT2 with GNAT3 - the third acetyltransferase within the NAA90 subfamily. This study unveils the existence of at least two acetyltransferase complexes within chloroplasts, whereby complex formation might have a critical effect on the fine-tuning of the overall acetyltransferase activities. These findings introduce a novel layer of regulation in acetylation-dependent adjustments in plastidial metabolism.
Fingerprints of ordered self-assembled structures in the liquid phase of a hard-core, square-shoulder system
2024-09-28

We investigate the phase ordering (pattern formation) of systems of two-dimensional core–shell particles using Monte Carlo (MC) computer simulations and classical density functional theory (DFT). The particles interact via a pair potential having a hard core and a repulsive square shoulder. Our simulations show that on cooling, the liquid state structure becomes increasingly characterized by long wavelength density modulations and on further cooling forms a variety of other phases, including clustered, striped, and other patterned phases. In DFT, the hard core part of the potential is treated using either fundamental measure theory or a simple local density approximation, whereas the soft shoulder is treated using the random phase approximation. The different DFTs are benchmarked using large-scale grand-canonical-MC and Gibbs-ensemble-MC simulations, demonstrating their predictive capabilities and shortcomings. We find that having the liquid state static structure factor S(k) for wavenumber k is sufficient to identify the Fourier modes governing both the liquid and solid phases. This allows us to identify from easier-to-obtain liquid state data the wavenumbers relevant to the periodic phases and to predict roughly where in the phase diagram these patterned phases arise.
Non-extractable residues of perfluorooctanoic acid (PFOA) in soil
2024-09-28

PER: and polyfluoroalkyl substances have gained increased attention due to their persistence, ubiquitous presence in the environment, and toxicity. We hypothesised that the formation of non-extractable residues [NER] occurs in soils and contributes to the overall persistence of these priority pollutants, and that NER formation is controlled by temperature. To test these hypotheses, we used <sup>14</sup>C-labelled perfluorooctanoic acid [PFOA] as target compound, added it to two arable soils (Cambisol, Luvisol), and incubated them at 10 °C and 20 °C in the dark. To support potential co-metabolic decomposition, some samples were additionally fed with glucose to enhance microbial activity. The PFOA residues were then sequentially extracted using 0.01 M CaCl<sub>2</sub>, followed by accelerated solvent extraction (ASE) with methanol or methanol/acetic acid after 0, 1, 3, 9, 30, 62, and 90 days of incubation. In addition, we monitored the release of <sup>14</sup>C into the gas phase as well as [<sup>14</sup>C]-PFOA-NER after dry combustion and liquid scintillation counting. After 90 days, we found that the [<sup>14</sup>C]-PFOA content declined in the extraction order of CaCl<sub>2</sub> ((bio)available fraction) > ASE (residual fraction) > NER > gas fraction), with most rapid changes occurring in the first 9 days of incubation. NER formation was different in the two soils and reached 5-9% of the applied amount in the Cambisol and Luvisol, respectively. Noteworthy the proportion of <sup>14</sup>C-PFOA in the (bio)available fraction remained relatively stable over time at 56-62% of the applied amount, indicating the reversible transfer into this fraction from a bi-exponentially declining residual (ASE) pool. These dissipation patterns were neither influenced by temperature nor by the addition of glucose. We conclude that NER exist for PFOA, but that the majority of PFOA remains in (bio)available form, thus maintaining toxicity and mobility in soil for prolonged periods of time.
TSS-Captur: a user-friendly pipeline for characterizing unclassified RNA transcripts
2024-09-28

Abstract RNA-seq and its 5′-enrichment methods for prokaryotes have enabled the precise identification of transcription start sites (TSSs), improving gene expression analysis. Computational methods are applied to these data to identify TSSs and classify them based on proximal annotated genes. While some TSSs cannot be classified at all (orphan TSSs), other TSSs are found on the reverse strand of known genes (antisense TSSs) but are not associated with the direct transcription of any known gene. Here, we introduce TSS-Captur, a novel pipeline, which uses computational approaches to characterize genomic regions starting from experimentally confirmed but unclassified TSSs. By analyzing TSS data, TSS-Captur characterizes unclassified signals, complementing prokaryotic genome annotation tools. TSS-Captur categorizes extracted transcripts as either messenger RNA for genes with coding potential or non-coding RNA (ncRNA) for non-translated genes. Additionally, it predicts the transcription termination site for each putative transcript. For ncRNA genes, the secondary structure is computed. Moreover, all putative promoter regions are analyzed to identify enriched motifs. An interactive report allows seamless data exploration. We validated TSS-Captur with a Campylobacter jejuni dataset and characterized unlabeled ncRNAs in Streptomyces coelicolor. TSS-Captur is available both as a web-application and as a command-line tool.
Levodopa / opicapone as a complement to STN-DBS in clinical practice. A retrospective single-centre analysis.
2024-09-28

These results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.
Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study
2024-09-29

Abstract The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM‐SDF) was effective and well tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents, and children in a multinational, prospective, randomized, active‐controlled Phase II study conducted between August 2017 and June 2021 (EudraCT 2020‐003284‐25, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here. The trial comprised three parts: a run‐in part in 12 adult/adolescent patients treated with a single dose of ganaplacide 200 mg plus LUM‐SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult/adolescent patients received one of the six ganaplacide‐LUM‐SDF regimens or artemether‐lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether‐lumefantrine, were assessed in children aged 2 to &lt;12 years, with body weight ≥10 kg. A rich blood sampling schedule was used for all 12 patients in the PK run‐in part and a subset of patients (N = 32) in Part A, with sparse sampling for remaining patients in Parts A (N = 275) and B (N = 159). Drug concentrations were determined by a validated protein precipitation and reverse phase liquid chromatography with tandem mass spectrometry detection method. Parameters including AUC inf , AUC last , AUC 0‐t , C max, and t max were reported where possible, using non‐compartmental analysis. In the PK run‐in part, there was no notable increase in ganaplacide or lumefantrine exposure when co‐administered. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was numerically under dose‐proportional. Lumefantrine exposure was higher with ganaplacide‐LUM‐SDF than with artemether‐lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures ( C max and AUC 0‐24 h ) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions.