julilili42/papers huggingface dataset:
Crosstalk between keratinocytes and neutrophils shapes skin immunity against S. aureus infection
2024-02-16

Introduction Staphylococcus aureus ( S. aureus ) infection of the skin leads to a rapid initial innate immune response with keratinocytes in the epidermis as the initial sensors. Polymorphonuclear neutrophils (PMNs) are the first innate immune cells to infiltrate infection sites where they provide an effective first-line of defense. Previous work of our group showed that in inflamed skin a crosstalk between PMNs and keratinocytes results in enhanced S. aureus skin colonization. Methods In this work, we used an in vitro co-culture model to studied the crosstalk between primary human keratinocytes (PHKs) and PMNs in a sterile environment and upon S. aureus infection. We investigated the influence of PHKs on PMN activation by analyzing PMN lifespan, expression of degranulation markers and induction of proinflammatory cytokines. Furthermore, we analyzed the influence of PMNs on the inflammatory response of PHKs. Finally, we investigated the influence of the skin microbiome on PMN-mediated skin inflammation. Results We show that co-culture of PMNs with PHKs induces activation and degranulation of PMNs and significantly enhances their lifespan compared to PMN cultivation alone by an IL-8 mediated mechanism and, furthermore, primes PMNs for enhanced activity after S. aureus infection. The prolonged incubation with PMNs also induces inflammatory responses in PHKs which are further exacerbated in the presence of S. aureus and induces further PMN recruitment thus fueling skin inflammation. Interestingly, infection of PHKs with the skin commensal S. epidermidis reduces the inflammatory effects of PMNs in the skin and exhibits an anti-inflammatory effect. Discussion Our data indicate that skin infiltrating PMNs and PHKs influence each other in such a way to enhance skin inflammation and that commensal bacteria are able to reduce the inflammatory effect.
Associations between COVID-19 Pandemic-Related Overtime, Perceived Chronic Stress and Burnout Symptoms in German General Practitioners and Practice Personnel—A Prospective Study
2024-02-16

Background: The mental burdens of general practitioners (GPs) and practice assistants (PrAs) during the COVID-19 pandemic are well investigated. Work-related conditions like overtime are known to contribute to perceived chronic stress and burnout symptoms. However, there is limited evidence regarding the specific mechanisms, which link pandemic-related overtime, chronic stress and burnout symptoms. This study used data from the IMPROVEjob trial to improve psychological well-being in general practice personnel. Methods: This prospective study with 226 German GPs and PrAs used the baseline (pre-pandemic: October 2019 to March 2020) and follow-up data (pandemic: October 2020 to April 2021) of the IMPROVEjob trial. Overtime was self-reported as hours above the regular work time. Perceived chronic stress was assessed using the Trier Inventory for the Assessment of Chronic Stress Screening Scale (TICS-SSCS), while burnout symptoms were evaluated using a short version of the Maslach Burnout Inventory (MBI). A mediation analysis investigated the differences of the three main variables between pre-pandemic and pandemic periods. Results: Burnout symptoms increased significantly from baseline to follow-up (p = 0.003). Overtime correlated positively with burnout symptoms (Total Effect: 0.13; 95% CI: 0.03, 0.23). Decomposition of the total effect revealed a significant indirect effect over perceived chronic stress (0.11; 95% CI: 0.06, 0.18) and no significant direct effect (0.02; 95% CI: −0.08, 0.12), indicating a full mediation. Conclusion: In this large longitudinal study, pandemic-related overtime led to significantly higher levels of burnout symptoms, linked by a pathway through perceived chronic stress. Future prevention strategies need to aim at reducing the likelihood of overtime to ensure the mental well-being of practice personnel.
Discovery of common molecular signatures and drug repurposing for COVID-19/Asthma comorbidity: ACE2 and multi-partite networks
2024-02-16

Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins - namely, <i>HRAS, IFNG, JUN, CDH1, TLR4, ICAM1</i>, and <i>SCD</i>-were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited <i>ICAM1</i> expression in the HDM-stimulated mice group (<i>p</i> < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.
Longitudinal associations between preschool children’s theory of mind, emotion understanding, and positive peer relationships
2024-02-16

The positive links between children’s theory of mind (ToM), emotion understanding, and positive peer relationships are well established. However, the existing literature lacks comprehensive studies investigating the longitudinal interplay between these components in preschool-aged children. This study aimed to fill this gap by examining the concurrent and longitudinal associations between young children’s social cognition and their positive peer relationships at three different time points over the course of 7 months. A sample of 211 preschool children (age in months: M T1 = 43.2, SD T1 = 6.6) underwent standardized assessments evaluating their ToM and emotion understanding, while playgroup educators reported on children’s positive peer relationships. Using multivariate latent growth modeling, we expected to find that higher levels of ToM and emotion understanding would be associated with a greater rate of change in positive peer relationships and that higher levels of positive peer relationships would be associated with a higher rate of change in ToM and emotion understanding. Contrary to our expectations, the results did not support the anticipated longitudinal associations. Nevertheless, a noteworthy correlation emerged between children’s emotion understanding and positive peer relationships at T1, in line with previous research and social-constructivist theories.
Comment on egusphere-2023-2789
2024-02-16

<strong class="journal-contentHeaderColor">Abstract.</strong> Rainfall redistribution through the vegetation canopy plays a key role in the hydrological cycle. Although there have been studies on the heterogeneous patterns of rainfall redistribution in some ecosystems, the understanding of this process in different stages of forest succession remains insufficient. Therefore, this study investigated the change tendency of rainfall redistribution and rainwater chemistry in a subtropical succession forest area in South China, based on 22 years (2001&ndash;2022) of monitoring 740 valid rainfall events. Results showed that at the event scale throughfall ratio showed in order broadleaf forest (BF) &lt; mixed forest (MF) &lt; pine forest (PF), and stemflow ratio showed in order BF &gt; MF &gt; PF. At the interannual scale, annual gross rainfall considerably shifted over time, which directly induced the variable accumulation of annual throughfall and annual stemflow. In the last 22 years, annual variability of throughfall presented in order MF (<em>CV</em>, 9.7 %) &lt; BF (15.6 %) &lt; PF (16.1 %), and annual variability of stemflow presented in order MF (<em>CV</em>, 38.6 %) &lt; PF (50.9) &lt; BF (56.2 %). The spatial variability of stemflow was always greater than that of throughfall. Besides, the difference of rainwater chemistry fluxes (TN, TP and K<sup>+</sup>) among the three forest types were found and they changed over time. Throughfall was characterized with high chemistry fluxes compared to open rainfall followed by stemflow. On average, TN and TP fluxes of throughfall presented in order BF &lt; MF &lt; PF, while K<sup>+ </sup>flux of throughfall presented in order BF &gt; MF &gt; PF. The above results indicated that the patterns of rainfall redistribution often changed over time. The event-scale accumulation of throughfall and stemflow potentially induced the interannual-scale variability. Both water volume and chemistry of throughfall and stemflow depended on the effect of rainfall and forest factors. This study provided insight into the rainfall redistribution process by linking the long-term changing of rainfall pattern and subtropical forest succession sequence.
The Declaration of Helsinki in bioethics literature since the last revision in 2013
2024-02-17

Abstract The World Medical Association has announced that a new revision process of the Declaration of Helsinki has been started. This article will identify the criticisms that have been made in the bioethics literature, particularly since the last revision. In addition, criticisms are discussed that were made in the literature even before the last revision and have not fallen silent. The plausibility of the recommendation for a change in the Declaration of Helsinki is examined.
Can Fairness be Automated? Guidelines and Opportunities for Fairness-aware AutoML
2024-02-17

The field of automated machine learning (AutoML) introduces techniques that automate parts of the development of machine learning (ML) systems, accelerating the process and reducing barriers for novices. However, decisions derived from ML models can reproduce, amplify, or even introduce unfairness in our societies, causing harm to (groups of) individuals. In response, researchers have started to propose AutoML systems that jointly optimize fairness and predictive performance to mitigate fairness-related harm. However, fairness is a complex and inherently interdisciplinary subject, and solely posing it as an optimization problem can have adverse side effects. With this work, we aim to raise awareness among developers of AutoML systems about such limitations of fairness-aware AutoML, while also calling attention to the potential of AutoML as a tool for fairness research. We present a comprehensive overview of different ways in which fairness-related harm can arise and the ensuing implications for the design of fairness-aware AutoML. We conclude that while fairness cannot be automated, fairness-aware AutoML can play an important role in the toolbox of ML practitioners. We highlight several open technical challenges for future work in this direction. Additionally, we advocate for the creation of more user-centered assistive systems designed to tackle challenges encountered in fairness work. This article appears in the AI &amp; Society track.
High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge as Inhibitors of Plasmodium falciparum
2024-02-17

In this study, we identified three novel compound classes with potent activity against <i>Plasmodium falciparum</i>, the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing, and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against <i>Mycobacterium tuberculosis</i>. The close structural similarities of the active sites of the DXPS enzymes of <i>P. falciparum</i> and <i>M. tuberculosis</i> prompted investigation of their antiparasitic action, all classes display good cell-based activity. Through structure-activity relationship studies, we increased their antimalarial potency and two classes also show good metabolic stability and low toxicity against human liver cells. The most active compound <b>1</b> inhibits the growth of blood-stage <i>P. falciparum</i> with an IC<sub>50</sub> of 600 nM. The results from three different methods for target validation of compound <b>1</b> suggest no engagement of DXPS. All inhibitor classes are active against chloroquine-resistant strains, confirming a new mode of action that has to be further investigated.
Improving Well-Being and Fostering Health-Oriented Leadership among Leaders in Small and Medium-Sized Enterprises (SMEs): A Systematic Review
2024-02-17

Leaders of small and medium-sized enterprises (SMEs) are often confronted with specific burdens, which frequently result in increased levels of stress. Leadership behaviour, in turn, has a significant impact on employees’ health and performance. Using the Population, Intervention, Comparison, Outcome (PICO) method, we conducted a systematic literature search covering publications from 2002 to 2023 using PubMed, PsycInfo and Business Source Premier on stress-reducing and well-being-improving interventions for SME leaders. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess the methodological quality and risk of bias of the included studies regarding selection bias, study design, confounders, blinding, data collection, withdrawal and drop-out. Of the 3150 identified publications, 6 were included after screening. The studies varied in content (cognitive behavioural therapy [CBT]-based, psychoeducation, and mixed interventions) and approach (individual- and organisation-centred). Not all of the examined interventions provided significant outcomes. However, CBT-based and individualised approaches showed a positive trend in reducing SME leaders’ psychosocial stress and improving their well-being. Despite the limited data, it can be concluded that such interventions are beneficial for leaders and their specific needs. Future research should focus on tailored approaches, derived from well-founded theories and integrative interventions addressing SME leaders.
Sampling at Groundwater–Surface Water Interfaces
2024-02-17

Analysis and assessment of the functioning of ecohydrological interfaces requires the ability to extract samples of water or sediment to characterize the interface properties and transport therein. Sample extraction from interfaces between groundwater on the one side and rivers, lakes, or marine environments on the other side can thus be broadly categorized as: ex situ sampling methods/coring methods; active in situ sampling methods; and passive in situ sampling methods. The principles of different sampling methods, their potential applications, advantages and disadvantages are discussed. The development of the sampling methods is primarily driven by the motivation to capture the steep biogeochemical, biological, and physical gradients encountered at groundwater–surface water interfaces. Recent developments, such as the sediment bed passive flux meter that allows the simultaneous assessment of both water and contaminant flux, seek to overcome this issue, but further testing under field conditions is required.
mgPGPT: Metagenomic analysis of plant growth-promoting traits
2024-02-18

In a recent publication, we introduce the PGPT ontology and PGPT-db of bacterial plant growth-promotion traits and associated database of protein sequences, and provide several tools for bacterial genome analysis on the PLaBAse server. Here, we extend the scope of the PGPT ontology to perform PGPT analysis of metagenomic datasets. First, we introduce mgPGPT-db, an extended database of 39, 582, 183 protein sequences obtained computationally by including proteins from AnnoTree. With this, we have integrated the PGPT ontology into our metagenome analysis tool MEGAN and provide mapping files to identify PGPT-related genes using the results of a DIAMOND alignment of reads against either the new mgPGPT-db database, the NCBI-nr protein database, or the AnnoTree protein database. We demonstrate and compare these different approaches in detail on an example data set and evince the improvement compared to the PGPT-db. We also compare the inferred PGPT content of several samples taken from different environments and reveal plant specific PGPT clustering. IMPORTANCE: A deeper understanding of plant growth-promoting traits of bacteria is important to enlight and enhance the native plant-beneficial bacterial functional diversity regarding the environmental stress adaption or the ability to suppress even food-borne pathogens by strain inoculation dedicated to agriculture and other plant production systems. The work presented here extends recent work beyond the analysis of individual to allow the assessment of the PGPT potential of metagenomes obtained from environmental samples.
Neuroradiological findings in GAA-FGF14ataxia (SCA27B): more than cerebellar atrophy
2024-02-18

Abstract Background GAA- FGF14 ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the FGF14 gene. Initial studies revealed cerebellar atrophy in 74-97% of patients. A more detailed brain imaging characterization of GAA- FGF14 ataxia is now needed to provide supportive diagnostic features and earlier disease recognition. Methods We performed a retrospective review of the brain MRIs of 35 patients (median age at MRI 63 years; range 28-88 years) from Quebec (n=27), Nancy (n=3), Perth (n=3) and Bengaluru (n=2) to assess the presence of atrophy in vermis, cerebellar hemispheres, brainstem, cerebral hemispheres, and corpus callosum, as well as white matter involvement. Following the identification of the superior cerebellar peduncles (SCPs) involvement, we verified its presence in 54 GAA- FGF14 ataxia patients from four independent cohorts (Tübingen n=29; Donostia n=12; Innsbruck n=7; Cantabria n=6). To assess lobular atrophy, we performed quantitative cerebellar segmentation in 5 affected subjects with available 3D T1-weighted images and matched controls. Results Cerebellar atrophy was documented in 33 subjects (94.3%). We observed SCP involvement in 22 subjects (62.8%) and confirmed this finding in 30/54 (55.6%) subjects from the validation cohorts. Cerebellar segmentation showed reduced mean volumes of lobules X and IV in the 5 affected individuals. Conclusions Cerebellar atrophy is a key feature of GAA- FGF14 ataxia. The frequent SCP involvement observed in different cohorts may facilitate the diagnosis. The predominant involvement of lobule X correlates with the frequently observed downbeat nystagmus.
Unifying principles of generalization: past, present, and future
2024-02-19

Generalization, defined as applying limited experiences to novel situations, represents a cornerstone of human intelligence. Our review traces the evolution and continuity of psychological theories of generalization, from origins in concept learning (categorizing stimuli) and function learning (learning continuous input-output relationships), to domains such as reinforcement learning and latent structure learning. Historically, there have been fierce debates between rule-based mechanisms, which rely on explicit hypotheses about environmental structure, and similarity-based mechanisms, which leverage comparisons to prior instances. Each approach has unique advantages: rules support rapid knowledge transfer, while similarity is computationally simple and flexible. Today, these debates have culminated in the development of hybrid models grounded in Bayesian principles, effectively marrying the precision of rules with the flexibility of similarity. The ongoing success of hybrid models not only bridges past dichotomies but also underscores the importance of integrating both rules and similarity for a comprehensive understanding of human generalization.
Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance
2024-02-19

Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC); the inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1β and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. The study included two independent cohorts of n = 92 and n = 102 patients who underwent a radical cystectomy for BC. Specimen from BC and benign urothelium (n = 22 and n = 39) were processed to a tissue microarray and immunohistochemically stained for IL-1β, IL-1RA, AKT, and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. An association with outcome was assessed using Wilcoxon Kruskal–Wallis tests, Chi-square tests or linear regression, dependent on the variable’s category. Kaplan–Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Both IL-1β and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p &lt; 0.005). IL-1β was associated with vascular invasion (210 vs. 183, p &lt; 0.02), lymphatic invasion (210 vs. 180, &lt;0.05) and G3 cancer (192 vs. 188, &lt;0.04). The survival analysis revealed favorable RFS, CSS, and OS in the case of high IL-1β expression (p &lt; 0.02, &lt;0.03, and &lt;0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1β expression on RFS, CSS, and OS. The IL-1β and IL-1β/IL-1RA ratios were positively correlated to the AKT expression (p &lt; 0.05 and &lt;0.01, respectively). Additionally, the high expression of Ki-67 (&gt;15%) correlated with higher levels of IL-1β (p = 0.01). The overexpression of IL-1β and IL-1RA is frequently found in BC, with a prognostic significance observed for the IL-1β protein expression. The observed link between the IL-1β/IL-1RA axis and AKT signaling may indicate possible autophagy activation processes besides the known tumor-promoting effects of AKT.