julilili42/papers huggingface dataset:
Examining how social activities influence pertussis. An application of random forest regression
2023-05-18

Relatively few epidemiological studies have utilized Random Forests (RF), possibly because the time series data often encountered in this discipline are perceived as unsuitable for supervised learning methods. We show RF can be used for such data, and demonstrate an example examining which social activities influence pertussis. Results are compared with regression with ARIMA errors modelling. Pertussis continues to be perceived as a childhood condition, despite recent incidence increases in older ages. COVID-19 provided a unique situation; social restrictions were implemented and the number of pertussis cases declined. This meant the influence of different activities on transmission could be gauged. Data detailing restrictions was used from the Oxford 'COVID-19 Government Response Tracker' (OxCGRT). The number of cases of pertussis and OxGCRT variables were lagged then embedded into a matrix, before being fitted into a RF regression model. Based on VIMP, this identified ‘international travel’ ‘public events’ and ‘workplace’ as the most important variables, suggesting adult based activities may be of most importance. An ARIMA(1,0,1), using OxCGRT categories as external regressors, similarly indicated that adult social activities better accounted for the number of cases of pertussis.
How to communicate with patients in written asynchronous online conversations: an intervention study with undergraduate medical students in a cross-over design
2023-05-18

Introduction The patient-physician encounter is the core element in the treatment of patients and the diagnosis of disease. In these times of digitalization, patient-physician communication is increasingly taking place online: patients embrace new possibilities offered digitally, and physicians are encouraged to adapt accordingly. Since a huge part of online communication is written, this study aims to investigate how medical students communicate with patients online by focusing on their written competencies and whether an intervention might improve their competencies. Methods This study was performed in an explanatory cross-sectional manner with a cross-over design. Second-year medical students participated. An intervention was developed on how to formulate an appropriate written response to a patient’s request and integrated a longitudinal communication class. The intervention consists of education on general set-up (e.g., greetings), syntax, spelling, content and kind of communication (e.g., appreciative attitude). After meeting a patient in a simulated role play medical students received the patient’s request via a digital platform. The control group had the same simulated role play and the same task but they received the intervention on communication afterwards. Intervention and control group were statistically compared based on a checklist. Results Twenty-nine medical students took part in the study. The results showed that the medical students had basic competencies in dealing with written communication independent if they received the intervention (CG: M = 3.86 ± 1.23 vs. IG: M = 4.07 ± 1.03; p = 0.625). Similar results were also for the emotional competency ratings (M CG = 3.36 ± 1.08; M IG = 3.67 ± 0.98; p = 0.425).The intervention was able to lead to a more appreciative response toward patient. Discussion Intervention on basic competencies such as simple language and clear presentation might not be needed as an integral part in medical education. However, medical students should learn how to present empathic and authentic behavior in written online communication.
General Continuity Bounds for Quantum Relative Entropies
2023-05-18

In this article, we generalize a proof technique by Alicki, Fannes and Winter and introduce a method to prove continuity bounds for entropic quantities derived from different quantum relative entropies. For the Umegaki relative entropy, we mostly recover known almost optimal bounds, whereas, for the Belavkin-Staszewski relative entropy, our bounds are new. Finally, we use these continuity bounds to derive a new entropic uncertainty relation.
FunARTS, the Fungal bioActive compound Resistant Target Seeker, an exploration engine for target-directed genome mining in fungi
2023-05-19

Abstract There is an urgent need to diversify the pipeline for discovering novel natural products due to the increase in multi-drug resistant infections. Like bacteria, fungi also produce secondary metabolites that have potent bioactivity and rich chemical diversity. To avoid self-toxicity, fungi encode resistance genes which are often present within the biosynthetic gene clusters (BGCs) of the corresponding bioactive compounds. Recent advances in genome mining tools have enabled the detection and prediction of BGCs responsible for the biosynthesis of secondary metabolites. The main challenge now is to prioritize the most promising BGCs that produce bioactive compounds with novel modes of action. With target-directed genome mining methods, it is possible to predict the mode of action of a compound encoded in an uncharacterized BGC based on the presence of resistant target genes. Here, we introduce the ‘fungal bioactive compound resistant target seeker’ (FunARTS) available at https://funarts.ziemertlab.com. This is a specific and efficient mining tool for the identification of fungal bioactive compounds with interesting and novel targets. FunARTS rapidly links housekeeping and known resistance genes to BGC proximity and duplication events, allowing for automated, target-directed mining of fungal genomes. Additionally, FunARTS generates gene cluster networking by comparing the similarity of BGCs from multi-genomes.
A novel multi-antigenic parapoxvirus-based vaccine demonstrates efficacy in protecting hamsters and non-human primates against SARS-CoV-2 challenge
2023-05-19

<title>Abstract</title> The next generation of COVID-19 vaccines needs to broaden the antigenic repertoire to improve breadth of immune response and efficacy against emerging variants of concern. This study describes a new parapoxvirus-based vector (ORFV) as a platform to design a multi-antigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Two vaccine candidates were engineered, one expressing spike protein alone (ORFV-S) and the other co-expressing the more conserved nucleocapsid protein (ORFV-S/N). Both vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. In a SARS-CoV-2 challenge model in hamsters, the multi-antigenic ORFV-S/N vaccine conferred protection in the upper and lower respiratory tract, while the ORFV-S-vaccinated animals showed protection restricted to the lungs. Similarly, in a non-human primates challenge model, vaccination with the ORFV-S/N vaccine resulted in rapid onset and long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of ORFV as a platform for prophylactic vaccination and support ongoing first-in-man studies with the multi-antigenic ORFV vaccine.
Threat and reactions to violated expectations in groups: Adding control to the equation
2023-05-19

Group members frequently face violations of group-based expectations by in- and outgroup members' behaviour. Responses to such violations include confronting the violators and escaping from the group. The current article presents a novel, integrative model explaining how and why violations of group-based expectations elicit these reactions. We argue that group members experience violations of expectations as threats to their social selves, which motivates them to react at all. Crucially adding to extant theorising, we argue that how group members react depends on their perceived control, a largely overlooked factor thus far. Herein, we synthesise our model's empirical basis, which spans studies on different violations (violations of ingroup norms, norms for cooperation, and expectations based on political ideology) and different group contexts (e.g., attitude-based lab groups, learning groups, Facebook groups). Moreover, we discuss boundary conditions for the model's applicability and its potential for integration with classic research on social identity management.
Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease
2023-05-19

Lysine residues are one of the main sites for posttranslational modifications of proteins, and lysine ubiquitination of the Machado-Joseph disease protein ataxin-3 is implicated in its cellular function and polyglutamine expansion-dependent toxicity. Despite previously undertaken efforts, the individual roles of specific lysine residues of the ataxin-3 sequence are not entirely understood and demand further analysis. By retaining single lysine residues of otherwise lysine-free wild-type and polyglutamine-expanded ataxin-3, we assessed the effects of a site-limited modifiability on ataxin-3 protein levels, aggregation propensity, localization, and stability. We confirmed earlier findings that levels of lysine-free ataxin-3 are reduced due to its decreased stability, which led to a diminished load of SDS-insoluble species of its polyglutamine-expanded form. The isolated presence of several single lysine residues within the N-terminus of polyglutamine-expanded ataxin-3 significantly restored its aggregate levels, with highest fold changes induced by the presence of lysine 8 or lysine 85, respectively. Ataxin-3 lacking all lysine residues presented a slightly increased nuclear localization, which was counteracted by the reintroduction of lysine 85, whereas presence of either lysine 8 or lysine 85 led to a significantly higher ataxin-3 stability. Moreover, lysine-free ataxin-3 showed increased toxicity and binding to K48-linked polyubiquitin chains, whereas the reintroduction of lysine 85, located between the ubiquitin-binding sites 1 and 2 of ataxin-3, normalized its binding affinity. Overall, our data highlight the relevance of lysine residues 8 and 85 of ataxin-3 and encourage further analyses, to evaluate the potential of modulating posttranslational modifications of these sites for influencing pathophysiological characteristics of the Machado-Joseph disease protein.
HIV infection and cardiovascular disease have both shared and distinct monocyte gene expression features: Women’s Interagency HIV study
2023-05-19

Persistent inflammation contributes to the development of cardiovascular disease (CVD) as an HIV-associated comorbidity. Innate immune cells such as monocytes are major drivers of inflammation in men and women with HIV. The study objectives are to examine the contribution of circulating non-classical monocytes (NCM, CD14 dim CD16 + ) and intermediate monocytes (IM, CD14 + CD16 + ) to the host response to long-term HIV infection and HIV-associated CVD. Women with and without chronic HIV infection (H) were studied. Subclinical CVD (C) was detected as plaques imaged by B-mode carotid artery ultrasound. The study included H-C-, H+C-, H-C+, and H+C+ participants (23 of each, matched on race/ethnicity, age and smoking status), selected from among enrollees in the Women’s Interagency HIV Study. We assessed transcriptomic features associated with HIV or CVD alone or comorbid HIV/CVD comparing to healthy (H-C-) participants in IM and NCM isolated from peripheral blood mononuclear cells. IM gene expression was little affected by HIV alone or CVD alone. In IM, coexisting HIV and CVD produced a measurable gene transcription signature, which was abolished by lipid-lowering treatment. In NCM, versus non-HIV controls, women with HIV had altered gene expression, irrespective of whether or not they had comorbid CVD. The largest set of differentially expressed genes was found in NCM among women with both HIV and CVD. Genes upregulated in association with HIV included several potential targets of drug therapies, including LAG3 (CD223). In conclusion, circulating monocytes from patients with well controlled HIV infection demonstrate an extensive gene expression signature which may be consistent with the ability of these cells to serve as potential viral reservoirs. Gene transcriptional changes in HIV patients were further magnified in the presence of subclinical CVD.
Environmental heterogeneity promotes coexistence among plant life-history strategies through stabilizing mechanisms in space and time
2023-05-19

Spatiotemporal environmental heterogeneity can promote species coexistence through stabilizing mechanisms such as the storage effect. These mechanisms require low density advantages and species-specific responses to heterogeneity. Theory based on organisms, which are short-lived and capitalize beneficial patches instantaneously, suggests that in the presence of spatiotemporal heterogeneity, stabilizing mechanisms should arise more commonly in space than in time.We used an individual-based model to investigate if spatiotemporal soil water heterogeneity promotes stable coexistence among annual and perennial plant life-history strategies, and which functional traits explain the requirements. Scenarios explicitly differed in the resource benefits offered by the range of soil water used to simulate heterogeneity.Our results show that spatiotemporal heterogeneity promoted stable coexistence solely among perennial life-history strategies. Perennial life form delayed population responses to heterogeneity, which resulted in population decoupling among life-history strategies in time as well as in space. Recovery from low density could be explained by a combination of one classical trait which stores the effects of favorable environmental conditions (longevity) and, unexpectedly, a fast resource acquisition strategy evidenced by high adult growth rate and short-term dormancy. Life-history strategy-specific responses emerged from functional differences in seedling competitive ability and seed dispersal distance alone or, additionally, from differences in the hydrological niche. Interestingly, life-history strategies which functionally differed only in dispersal distance coexisted irrespective of whether they experienced a difference in resource benefits themselves or coexisted with life-history strategies experiencing this difference.We show that spatiotemporal heterogeneity in a single abiotic factor promoted stable coexistence through stabilizing mechanisms. Our study highlights the need to study stabilizing mechanisms across different life-history strategies to better understand the effectiveness and dimensions of spatiotemporal heterogeneity in promoting coexistence.
Enhanced Airway Epithelial Response to SARS-CoV-2 Infection in Children is Critically Tuned by the Cross-Talk Between Immune and Epithelial Cells
2023-05-19

Abstract To cope with novel virus infections to which no prior adaptive immunity exists, the body strongly relies on the innate immune system. In such cases, including infections with SARS-CoV-2, children tend to fair better than adults. In the context of COVID-19, it became evident that a rapid interferon response at the site of primary infection is key for successful control of the virus and prevention of severe disease. The airway epithelium of children was shown to exhibit a primed state already at homeostasis and to respond particularly well to SARS-CoV-2 infection. However, the underlying mechanism for this priming remained elusive. Here we show that interactions between airway mucosal immune cells and epithelial cells are stronger in children, and via cytokine-mediated signaling lead to IRF-1-dependent upregulation of the viral sensors RIG-I and MDA5. Based on a cellular in vitro model we show that stimulated human peripheral blood mononuclear cells (PBMC) can induce a robust interferon-beta response towards SARS-CoV-2 in a lung epithelial cell line otherwise unresponsive to this virus. This is mediated by type I interferon, interferon-gamma and TNF, and requires induction of both, RIG-I and MDA5. In single cell-analysis of nasal swab samples the same cytokines are found to be elevated in mucosal immune cells of children, correlating with elevated epithelial expression of viral sensors. In vitro analysis of PBMC derived from healthy adolescents and adults confirm that immune cells of younger individuals show increased cytokine production and potential to prime epithelial cells. In co-culture with SARS-CoV-2-infected A549 cells, PBMC from adolescents significantly enhance the antiviral response. Taken together, our study suggests that higher numbers and a more vigorous activity of innate immune cells in the airway mucosa of children tune the set-point of the epithelial antiviral system. This likely is a major contributor to the robust immune response to SARS-CoV-2 in children. Our findings shed light on the molecular underpinnings of the stunning resilience of children towards severe COVID-19, and may propose a novel concept for immunoprophylactic treatments.
Electronic appendix to: Organic matter matters - The imaginary conductivity of sediments rich in solid organic carbon
2023-05-19

This is the electronic appendix to the publication C.Strobel, M. Doerrrich, E.-H. Stieff, J. A. Huisman, O.A. Cirpka, A. Mellage (2023): Organic matter matters - The imaginary conductivity of sediments rich in solid organic carbon (submitted)
Electronic appendix to: Organic matter matters - The imaginary conductivity of sediments rich in solid organic carbon
2023-05-19

This is the electronic appendix to the publication C.Strobel, M. Doerrrich, E.-H. Stieff, J. A. Huisman, O.A. Cirpka, A. Mellage (2023): Organic matter matters - The imaginary conductivity of sediments rich in solid organic carbon, Geophysical Research Letters
Energy Guided Diffusion for Generating Neurally Exciting Images
2023-05-20

Abstract In recent years, most exciting inputs (MEIs) synthesized from encoding models of neuronal activity have become an established method to study tuning properties of biological and artificial visual systems. However, as we move up the visual hierarchy, the complexity of neuronal computations increases. Consequently, it becomes more challenging to model neuronal activity, requiring more complex models. In this study, we introduce a new attention readout for a convolutional data-driven core for neurons in macaque V4 that outperforms the state-of-the-art task-driven ResNet model in predicting neuronal responses. However, as the predictive network becomes deeper and more complex, synthesizing MEIs via straightforward gradient ascent (GA) can struggle to produce qualitatively good results and overfit to idiosyncrasies of a more complex model, potentially decreasing the MEI’s model-to-brain transferability. To solve this problem, we propose a diffusion-based method for generating MEIs via Energy Guidance (EGG). We show that for models of macaque V4, EGG generates single neuron MEIs that generalize better across architectures than the state-of-the-art GA while preserving the within-architectures activation and requiring 4.7x less compute time. Furthermore, EGG diffusion can be used to generate other neurally exciting images, like most exciting natural images that are on par with a selection of highly activating natural images, or image reconstructions that generalize better across architectures. Finally, EGG is simple to implement, requires no retraining of the diffusion model, and can easily be generalized to provide other characterizations of the visual system, such as invariances. Thus EGG provides a general and flexible framework to study coding properties of the visual system in the context of natural images. 1
Practicing ubuntu
2023-05-20

Abstract This paper discusses one particular way we may put the idea of sharing in ubuntu philosophy into practice: moderate selflessness . Moderate selflessness is an important tool that might help us pursue other‐regarding behaviour alongside the agent's genuine well‐being interests to help disrupt the antagonistic gap between humanity and nonhumanity. I suggest that, properly understood, moderate selflessness may provide conceptual resources to avoid antagonistic environmental practices, including the concerns of poverty and biodiversity loss.
Mirror Therapy in Patients with Somatoform Pain Disorders—A Pilot Study
2023-05-20

Patients with chronic pain report reduced quality of life and high symptom burden while often responding insufficiently to treatment options. Mirror therapy has been proven to be effective in treating phantom limb pain and other conditions such as CRPS. This study was designed to investigate the efficacy of mirror therapy in patients with somatoform pain disorders on symptom severity and associated physiological parameters. Fifteen patients with persistent somatoform pain disorder (F45.40) or chronic pain disorder with somatic and psychological factors (F45.41) participated and received four weeks of tablet-based mirror therapy. Symptom severity was measured with established questionnaires, and their thermal detection, pain thresholds, and heart rate variability (HRV) were also assessed. After mirror therapy, pain intensity was reduced (z = −2.878, p = 0.004), and pain thresholds for cold stimuli were also diminished, i.e., the subjects became more sensitive to cold stimuli (z = −2.040, p = 0.041). In addition, a reduction of absolute power in the low-frequency band of HRV (t(13) = 2.536, p = 0.025) was detected. These findings indicate that this intervention may reduce pain intensity and modulate associated physiological parameters. As these results are limited by several factors, e.g., a small sample size and no control group, they should be validated in further studies investigating this novel intervention in these patients.
Neurosteroids Mediate Neuroprotection in an In Vitro Model of Hypoxic/Hypoglycaemic Excitotoxicity via δ-GABAA Receptors without Affecting Synaptic Plasticity
2023-05-21

Neurosteroids and benzodiazepines are modulators of the GABAA receptors, thereby causing anxiolysis. Furthermore, benzodiazepines such as midazolam are known to cause adverse side-effects on cognition upon administration. We previously found that midazolam at nanomolar concentrations (10 nM) blocked long-term potentiation (LTP). Here, we aim to study the effect of neurosteroids and their synthesis using XBD173, which is a synthetic compound that promotes neurosteroidogenesis by binding to the translocator protein 18 kDa (TSPO), since they might provide anxiolytic activity with a favourable side-effect profile. By means of electrophysiological measurements and the use of mice with targeted genetic mutations, we revealed that XBD173, a selective ligand of the translocator protein 18 kDa (TSPO), induced neurosteroidogenesis. In addition, the exogenous application of potentially synthesised neurosteroids (THDOC and allopregnanolone) did not depress hippocampal CA1-LTP, the cellular correlate of learning and memory. This phenomenon was observed at the same concentrations that neurosteroids conferred neuroprotection in a model of ischaemia-induced hippocampal excitotoxicity. In conclusion, our results indicate that TSPO ligands are promising candidates for post-ischaemic recovery exerting neuroprotection, in contrast to midazolam, without detrimental effects on synaptic plasticity.