julilili42/papers huggingface dataset:
Multitask Learning with Convolutional Neural Networks and Vision Transformers Can Improve Outcome Prediction for Head and Neck Cancer Patients
2023-10-09

Neural-network-based outcome predictions may enable further treatment personalization of patients with head and neck cancer. The development of neural networks can prove challenging when a limited number of cases is available. Therefore, we investigated whether multitask learning strategies, implemented through the simultaneous optimization of two distinct outcome objectives (multi-outcome) and combined with a tumor segmentation task, can lead to improved performance of convolutional neural networks (CNNs) and vision transformers (ViTs). Model training was conducted on two distinct multicenter datasets for the endpoints loco-regional control (LRC) and progression-free survival (PFS), respectively. The first dataset consisted of pre-treatment computed tomography (CT) imaging for 290 patients and the second dataset contained combined positron emission tomography (PET)/CT data of 224 patients. Discriminative performance was assessed by the concordance index (C-index). Risk stratification was evaluated using log-rank tests. Across both datasets, CNN and ViT model ensembles achieved similar results. Multitask approaches showed favorable performance in most investigations. Multi-outcome CNN models trained with segmentation loss were identified as the optimal strategy across cohorts. On the PET/CT dataset, an ensemble of multi-outcome CNNs trained with segmentation loss achieved the best discrimination (C-index: 0.29, 95% confidence interval (CI): 0.22–0.36) and successfully stratified patients into groups with low and high risk of disease progression (p=0.003). On the CT dataset, ensembles of multi-outcome CNNs and of single-outcome ViTs trained with segmentation loss performed best (C-index: 0.26 and 0.26, CI: 0.18–0.34 and 0.18–0.35, respectively), both with significant risk stratification for LRC in independent validation (p=0.002 and p=0.011). Further validation of the developed multitask-learning models is planned based on a prospective validation study, which has recently completed recruitment.
Digital gait measures capture 1-year progression in early-stage spinocerebellar ataxia type 2
2023-10-09

Abstract BACKGROUND With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. OBJECTIVE To unravel gait measures sensitive to longitudinal change in the - particularly trial-relevant- early stage of spinocerebellar ataxia type 2 (SCA2). METHODS Multi-center longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n=23, including 9 pre-ataxic expansion carriers; median ATXN2 CAG repeat expansion 38±2; median SARA [Scale for the Assessment and Rating of Ataxia] score 4.83±4.31). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focusing on gait measures of spatiotemporal variability shown sensitive to ataxia severity, e.g. lateral step deviation. RESULTS We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation p=0.0001, effect size r prb =0.78), whereas the SARA score showed no change (p=0.67). Sample size estimation indicates a required cohort size of n=43 to detect a 50% reduction in natural progression. Test-retest reliability and Minimal Detectable Change analysis confirm the accuracy of detecting 50% of the identified 1-year change. CONCLUSIONS Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just one year – in contrast to a clinical ataxia outcome. Lateral step deviation thus represents a promising outcome measure for upcoming multi-centre interventional trials, particularly in the early stages of cerebellar ataxia.
Cu(II) and Cd(II) Removal Efficiency of Microbially Redox-Activated Magnetite Nanoparticles
2023-10-09

Heavy metal pollutants in the environment are of global concern due to their risk of contaminating drinking water and food supplies. Removal of these metals can be achieved by adsorption to mixed-valent magnetite nanoparticles (MNPs) due to their high surface area, reactivity, and ability for magnetic recovery. The adsorption capacity and overall efficiency of MNPs are influenced by redox state as well as surface charge, the latter of which is directly related to solution pH. However, the influence of microbial redox cycling of iron (Fe) in magnetite alongside the change of pH on the metal adsorption process by MNPs remains an open question. Here we investigated adsorption of Cd<sup>2+</sup> and Cu<sup>2+</sup> by MNPs at different pH values that were modified by microbial Fe(II) oxidation or Fe(III) reduction. We found that the maximum adsorption capacity increased with pH for Cd<sup>2+</sup> from 256 μmol/g Fe at pH 5.0 to 478 μmol/g Fe at pH 7.3 and for Cu<sup>2+</sup> from 229 μmol/g Fe at pH 5.0 to 274 μmol/g Fe at pH 5.5. Microbially reduced MNPs exhibited the greatest adsorption for both Cu<sup>2+</sup> and Cd<sup>2+</sup> (632 μmol/g Fe at pH 7.3 for Cd<sup>2+</sup> and 530 μmol/g Fe at pH 5.5 for Cu<sup>2+</sup>). Magnetite oxidation also enhanced adsorption of Cu<sup>2+</sup> but inhibited Cd<sup>2+</sup>. Our results show that microbial modification of MNPs has an important impact on the (im-)mobilization of aqueous contaminations like Cu<sup>2+</sup> and Cd<sup>2+</sup> and that a change in stoichiometry of the MNPs can have a greater influence than a change of pH.
A New Biomarker Profiling Strategy for Gut Microbiome Research: Valid Association of Metabolites to Metabolism of Microbiota Detected by Non-Targeted Metabolomics in Human Urine
2023-10-09

The gut microbiome is of tremendous relevance to human health and disease, so it is a hot topic of omics-driven biomedical research. However, a valid identification of gut microbiota-associated molecules in human blood or urine is difficult to achieve. We hypothesize that bowel evacuation is an easy-to-use approach to reveal such metabolites. A non-targeted and modifying group-assisted metabolomics approach (covering 40 types of modifications) was applied to investigate urine samples collected in two independent experiments at various time points before and after laxative use. Fasting over the same time period served as the control condition. As a result, depletion of the fecal microbiome significantly affected the levels of 331 metabolite ions in urine, including 100 modified metabolites. Dominating modifications were glucuronidations, carboxylations, sulfations, adenine conjugations, butyrylations, malonylations, and acetylations. A total of 32 compounds, including common, but also unexpected fecal microbiota-associated metabolites, were annotated. The applied strategy has potential to generate a microbiome-associated metabolite map (M3) of urine from healthy humans, and presumably also other body fluids. Comparative analyses of M3 vs. disease-related metabolite profiles, or therapy-dependent changes may open promising perspectives for human gut microbiome research and diagnostics beyond analyzing feces.
Leveraging gaze for potential error prediction in AI-support systems: An exploratory analysis of interaction with a simulated robot
2023-10-09

With the increasing prevalence of AI–driven systems that assist humans in daily tasks, ensuring safety and fostering trust is pivotal. Moreover, addressing system errors is important, as conventional methods may be inaccessible and time consuming for people with motor impairments. This study explores implicit communication using eye-tracking features. We conducted a Virtual Reality (VR) experiment where participants used a robotic arm, encountering errors to be prevented through explicit communication. Findings reveal significant differences in eye-tracking features based on error recognition and demonstrate automated error detection feasibility. Using machine learning, we were able to classify when a user intends to stop the system before a potential collision using the eye features (86 – 90% accuracy). This research contributes to understanding eye movement behavior for error detection and offers insights for implementing implicit communication in AI –- driven assistive systems.
Transposon-triggered epigenetic chromatin dynamics modulate EFR-related pathogen response
2023-10-09

Summary Infectious diseases drive the evolution of wild plants and impact yield in crop plants. Like animals, plants can sense biotic threats via conserved pathogen-associated patterns (PAMPs). Since an overly robust immune response can harm plants, understanding the mechanisms for tuning defense responses to the appropriate level is vital as we endeavor to develop pathogen-resistant crops. In this paper, we studied the Arabidopsis pattern recognition receptor (PRR) EFR, which senses bacterial EF-Tu. An inverted-repeat transposon ( Ea-IR ) between EFR and the neighboring XI-k locus controls local chromatin organization, promoting the formation of a repressive chromatin loop. Upon pathogen infection, the chromatin landscape around EFR and Xl-k dynamically changes to allow for increased EFR transcription. Chromatin opening facilitates the passage of RNA polymerase II across the neighboring XI-k gene termination site, leading to a longer XI-k transcript that includes Ea-IR sequences. Dicer-like (DCL) enzymes process the longer Xl-k transcript into small RNAs (sRNAs), which reset chromatin topology to a repressive state, attenuating, in turn, the immune response, reminiscent of attenuation of receptor signaling in other systems. From an evolutionary point of view, we found that natural Arabidopsis accessions missing Ea-IR have a constitutive " EFR -open" chromatin configuration that correlates with higher basal EFR levels and higher background resistance to pathogens. Collectively, our study offers evidence for a scenario in which a transposon, chromatin organization, and gene expression interact to fine-tune immune responses, both during the course of infection and in the course of evolution. Similar gene-associated IRs in crops could provide valuable non-coding targets for genome editing or assisted plant breeding programs.
Unique distant classical Cepheid OGLE GD-CEP-1353 with anomalously high abundances of s- and r-process elements
2023-10-09

Aims . While looking for recently discovered distant Cepheids with an interesting chemical composition, we noticed one star (OGLE GD-CEP-1353) with extremely large equivalent widths of spectral lines of heavy elements. The aim of this work is to perform an abundance analysis, and to find a possible explanation for the found chemical anomaly. Methods . Quantitative analysis of the equivalent widths and synthetic spectrum synthesis were used to derive abundances in this star. Both local and nonlocal thermodynamic equilibrium (LTE and NLTE) approximations were used in our analysis. Results . Abundances of 28 chemical elements from carbon to thorium were derived. While light and iron peak elements show abundances typical for distant Cepheids (located in the outer disk), the s -process elements are overabundant about one dex. r -process elements are slightly less overabundant. This makes the star a unique Cepheid of our Galaxy.
Effects of Sound Immersion on In Vitro Blood Cells
2023-10-09

The effects of sound and mechanical vibrations on blood flow and in vitro and in vivo blood cells were previously reported in various studies. Frequency-based stimulation and sound vibrations were shown to have a positive effect on peripheral blood flow, blood aggregation, Red Blood Cells longevity and enhanced release of Nitric Oxide which supports improved blood oxygenation. Different frequencies were also reported to have discrete effects on cells and physiological mechanisms. In this preliminary study, we investigated the effect of 20 minutes exposure to audible sound stimuli comprising recordings of spatial sound projections of a singing bowl at 40 Hz and 73 Hz compared to 20 minutes silence in a Faraday cage (control) on in vitro Red Blood Cells and White Blood Cells. We find that the sound stimuli have a highly significant effect on the longevity of both Red and White Blood Cells with a differentiation in effect across frequencies and projections compared to control. Results could indicate a cost-effective treatment to support improved soundness of blood transfusions as well as non-invasive interventions to increase circulating blood cells.
Chapter 2 The Culture of Law
2023-10-09

The Question about the Marriages of those who by Blood or Affinity are related, is a nice and difficult Point, and which has frequently been managed pro and con, with no little Heat and Commotion.For whoever attempts to assign certain and natural Reasons why such Marriages are unwarrantable
Triptan non-response in specialized headache care: cross-sectional data from the DMKG Headache Registry
2023-10-10

Abstract Background Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans (‘triptan resistance’) could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of ‘triptan resistance’. Methods We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure. Results A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% ( n = 970) had failed ≥ 1 triptan, 13.1% ( n = 300) had failed ≥ 2 triptans (meeting the EHF definition of ‘triptan resistance’), and 3.9% ( n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency ( p &lt; 0.001), intensity ( p &lt; 0.05), and disability ( p &lt; 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan. Conclusion In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class. Trial registration The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).
Extensible benchmarking of methods that identify and quantify polyadenylation sites from RNA-seq data
2023-10-10

The tremendous rate with which data is generated and analysis methods emerge makes it increasingly difficult to keep track of their domain of applicability, assumptions, limitations, and consequently, of the efficacy and precision with which they solve specific tasks. Therefore, there is an increasing need for benchmarks, and for the provision of infrastructure for continuous method evaluation. APAeval is an international community effort, organized by the RNA Society in 2021, to benchmark tools for the identification and quantification of the usage of alternative polyadenylation (APA) sites from short-read, bulk RNA-sequencing (RNA-seq) data. Here, we reviewed 17 tools and benchmarked eight on their ability to perform APA identification and quantification, using a comprehensive set of RNA-seq experiments comprising real, synthetic, and matched 3′-end sequencing data. To support continuous benchmarking, we have incorporated the results into the OpenEBench online platform, which allows for continuous extension of the set of methods, metrics, and challenges. We envisage that our analyses will assist researchers in selecting the appropriate tools for their studies, while the containers and reproducible workflows could easily be deployed and extended to evaluate new methods or data sets.
Abstract perceptual choice signals during action-linked decisions in the human brain
2023-10-10

Humans can make abstract choices independent of motor actions. However, in laboratory tasks, choices are typically reported with an associated action. Consequentially, knowledge about the neural representation of abstract choices is sparse, and choices are often thought to evolve as motor intentions. Here, we show that in the human brain, perceptual choices are represented in an abstract, motor-independent manner, even when they are directly linked to an action. We measured MEG signals while participants made choices with known or unknown motor response mapping. Using multivariate decoding, we quantified stimulus, perceptual choice, and motor response information with distinct cortical distributions. Choice representations were invariant to whether the response mapping was known during stimulus presentation, and they occupied a distinct representational space from motor signals. As expected from an internal decision variable, they were informed by the stimuli, and their strength predicted decision confidence and accuracy. Our results demonstrate abstract neural choice signals that generalize to action-linked decisions, suggesting a general role of an abstract choice stage in human decision-making.
Intranasal Delivery of Oncolytic Adenovirus XVir-N-31 via Optimized Shuttle Cells Significantly Extends Survival of Glioblastoma-Bearing Mice
2023-10-10

A glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OVT) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the oncolytic virus (OV) is applied intratumorally. Using two xenograft GBM mouse models and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood–brain barrier (BBB). Our findings demonstrate that the INA of XVir-N-31-loaded shuttle cells successfully delivered OAVs to the core tumor and invasive GBM cells, significantly prolonged the survival of the GBM-bearing mice, induced immunogenic cell death and finally reduced the tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of the INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of the INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.
Ubuntu Thinking on Biodiversity Loss: The Inadequacies of Egalitarian and Communitarian Solutions
2023-10-10

ABSTRACT This article evaluates the moral implications of two leading theories on biodiversity preservation/conservation (Paul Taylor's biocentric egalitarianism and J. Baird Callicott's holistic communitarianism). Taylor argues for the moral equality of all members of the Earth's community of life, calling for an ethic of respect for nature to conserve biodiversity. Callicott argues for the moral consideration of ecosystems to maintain their integrity, stability, and beauty. The article makes two major claims. First, we need a plausible account of moral egalitarianism to disrupt ethical anthropocentrism. Second, the ethics of respect for nature requires a critical bottom‐up character‐based ethical theory to be morally forceful. These missing elements are central to the ubuntu philosophy about personhood and are significant for enriching egalitarian‐communitarian solutions to biodiversity loss.
Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis
2023-10-10

Abstract Aim Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis. Materials and Methods Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index &gt;36); elevated transaminases [alanine transaminase (ALT) &gt;33 (males) and &gt;25 IU/L (females)]; and fibrosis‐4 (FIB‐4) index scores &gt;3.25, &gt;2.67 and &gt;1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma‐glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke or hospitalization for heart failure. Results ALT, aspartate aminotransferase and gamma‐glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB‐4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB‐4 subgroups by 52% (&gt;3.25), 39% (&gt;2.67) and 24% (&gt;1.30) ( p values for interaction = .01, .13 and .03, respectively). Conclusions Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB‐4 scores who were at high risk of developing cardiovascular complications.
Are You Worried About Getting Covid-19 or About Losing Your Job?
2023-10-10

Although research showed that media consumption during Covid-19 is related to preventive behaviours, we know less about why people turn to quality or alternative media in the first place. We focus on the role of different fears. More specifically, we assumed that fears focusing on health threats were positively associated with the consumption of quality media and negatively with the consumption of tabloids and alternative media. We expected the opposite pattern for fears focusing on economic and societal threats, and that media consumption mediated the relationship between fears and vaccination acceptance. A survey among a representative sample of Germans (N = 1080) showed that the fears correlated as expected positively with the consumption of the respective media type. However, the predicted negative relationships with the other media type often turned out as non-significant. The fears were differentially related to vaccination acceptance via media consumption, indicating the theoretical and practical value of differentiating between different types of fears.