julilili42/papers huggingface dataset:
Visual Analytics of Multivariate Intensive Care Time Series Data
2022-04-13

Abstract We present an approach for visual analysis of high‐dimensional measurement data with varying sampling rates as routinely recorded in intensive care units. In intensive care, most assessments not only depend on one single measurement but a plethora of mixed measurements over time. Even for trained experts, efficient and accurate analysis of such multivariate data remains a challenging task. We present a linked‐view post hoc visual analytics application that reduces data complexity by combining projection‐based time curves for overview with small multiples for details on demand. Our approach supports not only the analysis of individual patients but also of ensembles by adapting existing techniques using non‐parametric statistics. We evaluated the effectiveness and acceptance of our approach through expert feedback with domain scientists from the surgical department using real‐world data: a post‐surgery study performed on a porcine surrogate model to identify parameters suitable for diagnosing and prognosticating the volume state, and clinical data from a public database. The results show that our approach allows for detailed analysis of changes in patient state while also summarizing the temporal development of the overall condition.
A novel PNGase Rc for improved protein N-deglycosylation in bioanalytics and HDX-MS epitope mapping under challenging conditions
2022-04-13

Abstract N-linked glycosylation is a ubiquitous posttranslational modification of proteins. While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating proteins due to sterically inaccessible N-glycosylation sites. This usually leads to poor sequence coverage in bottom-up analysis using liquid chromatography with tandem mass spectrometry (LC-MS) and makes it impossible to obtain an intact mass signal in top-down MS analysis. In addition, most PNGases operate optimally only in the neutral to slightly acidic pH range and are severely compromised in the presence of reducing and denaturing substances, which limits their use for advanced bioanalysis based on hydrogen-deuterium exchange in combination with mass spectrometry (HDX-MS). Here, we present a novel peptide N-glycanase from Rudaea cellulosilytica (PNGase Rc) for which we demonstrate broad substrate specificity for N-glycan hydrolysis from multiply occupied and natively folded proteins. Our results show that PNGase Rc is functional even under challenging, HDX quench conditions (pH 2.5, 0 °C) and in the presence of 0.4 M Tris(2-carboxyethyl)phosphine (TCEP), 4 M urea and 1 M guanidinium chloride (GdmCl). Most importantly, we successfully applied the PNGase Rc in an HDX-MS workflow to determine the epitope of a nanobody targeting the extracellular domain of human signal-regulating protein alpha (SIRPα).
Effects of plastic fragment size and concentration on plant performance are mediated by soil properties and water availability
2022-04-13

Abstract Purpose: Increasing attention has been devoted to the effects of plastic contamination on soil water content and plant performance. However, little is known about how plastic in soil may interact with climate change factors, such as drought. We hypothesized that 1) Plastic affects soil water content negatively, and such effect is mediated by plastic size and concentrations, water availability and soil texture; 2) plants attain higher growth in soil where the negative effects of drought and plastic are small. Methods: We tested the joint effects of water availability, soil texture, and plastic fragments (varying in concentration and size), on soil water content and growth of the model plant Arabidopsis thaliana . Results: While increasing concentrations and size of plastic negatively affected soil water content, likely by favoring the formation of fractures within soil aggregates, they positively affected plant growth, likely by increasing soil porosity and facilitating root growth. In low water availability such responses were generally stronger, while soil texture mediated linear vs. unimodal responses in soil water content. Conclusion: Plastic contamination in soil is bound to increase overtime, and it may interact with drought in affecting soil and plants in non-linear ways. This implies that plastic contamination may either amplify or mitigate the effects of climate change on plants, soil and their interactions.
Dataset of ipsilateral motor-evoked potentials induced by transcranial magnetic stimulation
2022-04-13

The dataset includes 2546 trials of EMG recordings after ipsilateral TMS under muscle contraction. This data was used for the evaluation of the DiMEP toolbox https://pypi.org/project/dimep/ All subjects provided written, informed consent before participation and following approval by the local ethics committee. Subjects had no contraindications to TMS. TMS was delivered with a MagVenture MagPro-R30 with MagOption and a MCF-B70 figure 8-coil at an orientation of 45° to the midsagittal plane (see figure 1A). First, the motor hotspot of the contralateral, i.e., right, extensor digitorum communis (EDC) was determined by applying 40 stimuli to the left hemisphere. 40% MSO was used as the starting intensity and increased in steps of 5% MSO in case no MEPs could be elicited. Next, at the locations of the three stimuli that resulted in the greatest MEP, i.e., the largest MEP peak-to-peak amplitude, additional three stimuli were applied. The stimulation location that consistently elicited the largest MEPs in the contralateral EDC was then selected as the hotspot. A neuro-navigation system (TMS Navigator, Localite GmbH, Germany) supported coil positioning throughout the measurements. In order to measure ipsilateral MEPs, TMS pulses were applied to the motor hotspot with 5s ± 1.25 s between pulses (at an intensity of 90% MSO). To increase the likelihood of exhibiting ipsilateral MEPs, subjects were requested to isometrically contract their left biceps brachii (BB) to 30% of its maximum voluntary contraction while receiving visual feedback of the BB activity relative to the required target level of contraction on a computer display. The electromyographical response (EMG) to TMS was recorded with a BrainProducts ExG bipolar amplifier from the ipsilateral EDC. All trials were divided into 1s segments, i.e., 500 ms before and after each TMS pulse, and sampled at 1000 Hz. We removed artifacts due to coil placement with a Heaviside fit removal, a Hampel filter of 20 ms width, and a polynomial detrending of 5<sup>th</sup> order. Trials with remaining artifacts were rejected, resulting in an average of 47 trials per subject.
Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer
2022-04-14

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896 ), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P &lt; .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.
Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma
2022-04-14

Abstract Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. Patients and Methods: A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints. Results: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. Conclusions: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I– and class II–restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.
The Leaf Microbiome of Arabidopsis Displays Reproducible Dynamics and Patterns throughout the Growing Season
2022-04-14

Utilizing plant microbiota to promote plant growth and plant health is key to more environmentally friendly agriculture. A major bottleneck in the engineering of plant-beneficial microbial communities is the low persistence of applied microbes under filed conditions, especially considering plant leaves.
psupertime: supervised pseudotime analysis for time-series single-cell RNA-seq data
2022-04-14

Abstract Motivation Improvements in single-cell RNA-seq technologies mean that studies measuring multiple experimental conditions, such as time series, have become more common. At present, few computational methods exist to infer time series-specific transcriptome changes, and such studies have therefore typically used unsupervised pseudotime methods. While these methods identify cell subpopulations and the transitions between them, they are not appropriate for identifying the genes that vary coherently along the time series. In addition, the orderings they estimate are based only on the major sources of variation in the data, which may not correspond to the processes related to the time labels. Results We introduce psupertime, a supervised pseudotime approach based on a regression model, which explicitly uses time-series labels as input. It identifies genes that vary coherently along a time series, in addition to pseudotime values for individual cells, and a classifier that can be used to estimate labels for new data with unknown or differing labels. We show that psupertime outperforms benchmark classifiers in terms of identifying time-varying genes and provides better individual cell orderings than popular unsupervised pseudotime techniques. psupertime is applicable to any single-cell RNA-seq dataset with sequential labels (e.g. principally time series but also drug dosage and disease progression), derived from either experimental design and provides a fast, interpretable tool for targeted identification of genes varying along with specific biological processes. Availability and implementation R package available at github.com/wmacnair/psupertime and code for results reproduction at github.com/wmacnair/psupplementary. Supplementary information Supplementary data are available at Bioinformatics online.
TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia
2022-04-14

Abstract The hereditary spastic paraplegias (HSP) are among the most genetically diverse of all Mendelian disorders. They comprise a large group of neurodegenerative diseases that may be divided into ‘pure HSP’ in forms of the disease primarily entailing progressive lower-limb weakness and spasticity, and ‘complex HSP’ when these features are accompanied by other neurological (or non-neurological) clinical signs. Here, we identified biallelic variants in the transmembrane protein 63C (TMEM63C) gene, encoding a predicted osmosensitive calcium-permeable cation channel, in individuals with hereditary spastic paraplegias associated with mild intellectual disability in some, but not all cases. Biochemical and microscopy analyses revealed that TMEM63C is an endoplasmic reticulum-localized protein, which is particularly enriched at mitochondria–endoplasmic reticulum contact sites. Functional in cellula studies indicate a role for TMEM63C in regulating both endoplasmic reticulum and mitochondrial morphologies. Together, these findings identify autosomal recessive TMEM63C variants as a cause of pure and complex HSP and add to the growing evidence of a fundamental pathomolecular role of perturbed mitochondrial-endoplasmic reticulum dynamics in motor neurone degenerative diseases.
Inspiration on social media: Applying an entertainment perspective to longitudinally explore mental health and well-being
2022-04-14

The conditions under which social media use impacts well-being and mental health are complex. The current 10-day longitudinal quasi-experiment (student sample, N = 111) applied an entertainment theory lens to explore the effects of active posting and engaging with hedonic or inspiring Facebook content (vs. passive browsing) on young people’s eudaimonic well-being (levels of connectedness to humanity, love, compassion, presence of meaning) and mental health (anxiety and depressive symptoms). The results provide tentative evidence that finding and sharing inspiring content to a Facebook group increased love and compassion toward others over time. It also led to more compassion at the end of the study compared to participants who shared hedonic content. Although we did not find an increase in connectedness and meaningfulness over time for participants sharing content that they found inspiring, the latter also did not take away from those experiences, regardless of how they used it. Similarly, no decrease—but also no increase—in anxiety and depressive symptoms were found over time, regardless of condition. The study stresses the importance of better understanding the content young adults engage with on social media for their mental health and well-being.
Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends
2022-04-14

Background Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects.
Changing knowledge and attitudes about childhood fever: testing a video instruction before its application in a health app
2022-04-14

Background: Although infantile fever is harmless in most cases, many parents feel insecure when having to deal with it because important information is often missing. For educational purposes, an information video on fever in children was developed, which is also intended to serve as an onboarding element of a health app. The aim of the present work was to record the attitude of parents and adults on the topic of fever before and after the presentation of the information video, as well as its evaluation. Methods: Between May and November 2020, a total of 123 adults from three groups with different backgrounds (students, parents and educators) were interviewed using a questionnaire that was completed before and after the one-time presentation of an educational information video clip. Results: Several significant outcomes were recorded in attitude change toward managing fever, with no significant difference between groups. After viewing the informational video clip, 74% of participants would take body temperature rectally more often. In the after-questionnaire, 83% of participants agreed that they would now be more cautious about using fever-reducing medications. Before the video clip, 75% of the participants thought fever was “rather useful”; after, 93%. The level of temperature played a minor role as a reason for fever reduction. The information content and quality of the video were rated positively. Discussion: This study shows that a short information video is capable of bringing about a subjectively perceived intentional change in the attitude to dealing with fever, motivating a change in behavior, and reducing uncertainty in dealing with fever. Since the change in attitude was measured immediately after viewing the video clip, no statement can be made about the medium to long-term effect. Conclusion: The information video clip can be classified as a short-term fever education tool for which at least short-term effective is demonstrated. Long-term and possible synergistic effects when integrated into a health app with further information still needs to be investigated.
Do-It-Yourself digital archaeology: Introduction and practical applications of photography and photogrammetry for the 2D and 3D representation of small objects and artefacts
2022-04-15

Photography and photogrammetry have recently become among the most widespread and preferred visualisation methods for the representation of small objects and artefacts. People want to see the past, not only know about it; and the ability to visualise objects into virtually realistic representations is fundamental for researchers, students and educators. Here, we present two new methods, the ‘Small Object and Artefact Photography’ (‘SOAP’) and the ‘High Resolution “DIY” Photogrammetry’ (‘HRP’) protocols. The ‘SOAP’ protocol involves the photographic application of modern digital techniques for the representation of any small object. The ‘HRP’ protocol involves the photographic capturing, digital reconstruction and three-dimensional representation of small objects. These protocols follow optimised step-by-step explanations for the production of high-resolution two- and three-dimensional object imaging, achievable with minimal practice and access to basic equipment and softwares. These methods were developed to allow anyone to easily and inexpensively produce high-quality images and models for any use, from simple graphic visualisations to complex analytical, statistical and spatial analyses.
Fluorogenic RNA-Based Biosensor to Sense the Glycolytic Flux in Mammalian Cells
2022-04-15

The visualization of metabolic flux in real time requires sensor molecules that transduce variations of metabolite concentrations into an appropriate output signal. In this regard, fluorogenic RNA-based biosensors are promising molecular tools as they fluoresce only upon binding to another molecule. However, to date no such sensor is available that enables the direct observation of key metabolites in mammalian cells. Toward this direction, we selected and characterized an RNA light-up sensor designed to respond to fructose 1,6-bisphosphate and applied it to probe glycolytic flux variation in mammal cells.