julilili42/papers huggingface dataset:
To whom do people reply in comment sections? Effects of attitude (un)congeniality, age, confidence, and knowledge
2024-04-22

Phenomena like echo chambers and societal polarization have often been linked to an individual preference for like-minded information (selective exposure). This view has been challenged recently: behavior on comment sections in online forums suggests the opposite dynamic, with users more likely to reply to attitudinally uncongenial content. Three experimental studies (total N = 1524) explore boundary conditions of this uncongeniality bias by measuring participants’ tendency to reply to comments on climate science. Studies 1 (student sample) and 2 (non-student sample) replicate the uncongeniality bias. However, Study 3 (representative for age and gender in Germany) yielded a surprising congeniality bias (a preference for replying to congenial comments) which was driven by participants with higher age. Further results across studies suggest that high confidence increases engagement (general likelihood to reply) but reduces antagonism (likelihood to reply to uncongenial content). Conversely, high knowledge reduces engagement but increases the uncongeniality bias.
Suppression PCR-Based Selective Enrichment Sequencing for Pathogen and Antimicrobial Resistance Detection on Cell-Free DNA in Sepsis - A Targeted, Blood Culture Independent Approach for Rapid Pathogen and Resistance Diagnostics in Septic Patients
2024-04-22

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.
Reply on RC1
2024-04-22

<strong class="journal-contentHeaderColor">Abstract.</strong> Radio-echo sounding is a standard technique for imaging the englacial stratigraphy of glaciers and ice sheets. In most cases, internal reflection horizons (IRHs) represent former glacier surfaces and comprise information about past accumulation, ice deformation and allow to link ice core chronologies. IRHs in the lower third of the ice column are often difficult to detect or coherently trace. In the polar ice sheets, progress in IRH detection has been made by using multistatic, phase-coherent radars, enabling synthetic-aperture radar (SAR) processing. However, these radar systems are often not suitable for deployment on mountain glaciers. We present a proof-of-concept study for a lightweight, phase-coherent, and ground-based radar system, based on the phase-sensitive radio echo-sounder (pRES). To improve the detectability of IRHs we additionally adapted a layer-optimized SAR (LO-SAR) processing scheme to this setup. We showcase the system capability at Colle Gnifetti, Switzerland/Italy, and detect significantly deeper and older IRHs compared to previously deployed pulsed radar systems. Continuous IRHs are now apparent down to the base of the glacier. Corresponding reflection mechanisms for this glacier are linked to a stratified acidic impurity which was deposited at a higher rate due to increased industrial activity in the area. Possible improvements of the system are discussed. If successfully implemented, these may provide a new way to map the deep internal structure of Colle Gnifetti and other mountain glaciers more extensively in future deployments.
Reply on RC2
2024-04-22

<strong class="journal-contentHeaderColor">Abstract.</strong> Radio-echo sounding is a standard technique for imaging the englacial stratigraphy of glaciers and ice sheets. In most cases, internal reflection horizons (IRHs) represent former glacier surfaces and comprise information about past accumulation, ice deformation and allow to link ice core chronologies. IRHs in the lower third of the ice column are often difficult to detect or coherently trace. In the polar ice sheets, progress in IRH detection has been made by using multistatic, phase-coherent radars, enabling synthetic-aperture radar (SAR) processing. However, these radar systems are often not suitable for deployment on mountain glaciers. We present a proof-of-concept study for a lightweight, phase-coherent, and ground-based radar system, based on the phase-sensitive radio echo-sounder (pRES). To improve the detectability of IRHs we additionally adapted a layer-optimized SAR (LO-SAR) processing scheme to this setup. We showcase the system capability at Colle Gnifetti, Switzerland/Italy, and detect significantly deeper and older IRHs compared to previously deployed pulsed radar systems. Continuous IRHs are now apparent down to the base of the glacier. Corresponding reflection mechanisms for this glacier are linked to a stratified acidic impurity which was deposited at a higher rate due to increased industrial activity in the area. Possible improvements of the system are discussed. If successfully implemented, these may provide a new way to map the deep internal structure of Colle Gnifetti and other mountain glaciers more extensively in future deployments.
Pregnancy and acromegaly: clinical outcomes of retrospectively analysed data from the German acromegaly registry
2024-04-22

Abstract Context Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child. Objective To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly. Design &amp; methods Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry. Results 87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications. Conclusion Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.
Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease
2024-04-23

Abstract Background Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease‐modifying therapies. Objective The aim was to evaluate a blood‐based α‐synuclein seed amplification assay (α‐syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. Methods In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α‐syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α‐syn‐SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. Results All individuals with PD showed positive immunoblots and a positive α‐syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α‐syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α‐syn SAA. All healthy controls had a negative SAA. Conclusions We here demonstrate the possibility to detect and amplify pathological α‐syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood‐based α‐syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Understanding and Perception of Automated Text Generation among the Public: Two Surveys with Representative Samples in Germany
2024-04-23

Automated text generation (ATG) technology has evolved rapidly in the last several years, enabling the spread of content produced by artificial intelligence (AI). In addition, with the release of ChatGPT, virtually everyone can now create naturally sounding text on any topic. To optimize future use and understand how humans interact with these technologies, it is essential to capture people’s attitudes and beliefs. However, research on ATG perception is lacking. Based on two representative surveys (March 2022: n1 = 1028; July 2023: n2 = 1013), we aimed to examine the German population’s concepts of and attitudes toward AI authorship. The results revealed a preference for human authorship across a wide range of topics and a lack of knowledge concerning the function, data sources, and responsibilities of ATG. Using multiple regression analysis with k-fold cross-validation, we identified people’s attitude toward using ATG, performance expectancy, general attitudes toward AI, and lay attitude toward ChatGPT and ATG as significant predictors of the intention to read AI-written texts in the future. Despite the release of ChatGPT, we observed stability across most variables and minor differences between the two survey points regarding concepts about ATG. We discuss the findings against the backdrop of the ever-increasing availability of automated content and the need for an intensive societal debate about its chances and limitations.
Transferability of Machine Learning Models for Crop Classification in Remote Sensing Imagery Using a New Test Methodology: A Study on Phenological, Temporal, and Spatial Influences
2024-04-23

Machine learning models are used to identify crops in satellite data, which achieve high classification accuracy but do not necessarily have a high degree of transferability to new regions. This paper investigates the use of machine learning models for crop classification using Sentinel-2 imagery. It proposes a new testing methodology that systematically analyzes the quality of the spatial transfer of trained models. In this study, the classification results of Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Stochastic Gradient Descent (SGD), Multilayer Perceptron (MLP), Support Vector Machines (SVM), and a Majority Voting of all models and their spatial transferability are assessed. The proposed testing methodology comprises 18 test scenarios to investigate phenological, temporal, spatial, and quantitative (quantitative regarding available training data) influences. Results show that the model accuracies tend to decrease with increasing time due to the differences in phenological phases in different regions, with a combined F1-score of 82% (XGBoost) when trained on a single day, 72% (XGBoost) when trained on the half-season, and 61% when trained over the entire growing season (Majority Voting).
Effects of Chemicals in Reporter Gene Bioassays with Different Metabolic Activities Compared to Baseline Toxicity
2024-04-23

High-throughput cell-based bioassays are used for chemical screening and risk assessment. Chemical transformation processes caused by abiotic degradation or metabolization can reduce the chemical concentration or, in some cases, lead to the formation of more toxic transformation products. Unaccounted loss processes may falsify the bioassay results. Capturing the formation and effects of transformation products is important for relating the <i>in vitro</i> effects to <i>in vivo.</i> Reporter gene cell lines are believed to have low metabolic activity, but inducibility of cytochrome P450 (CYP) enzymes has been reported. Baseline toxicity is the minimal toxicity a chemical can have and is caused by the incorporation of the chemical into cell membranes. In the present study, we improved an existing baseline toxicity model based on a newly defined critical membrane burden derived from freely dissolved effect concentrations, which are directly related to the membrane concentration. Experimental effect concentrations of 94 chemicals in three bioassays (AREc32, ARE-<i>bla</i> and GR-<i>bla</i>) were compared with baseline toxicity by calculating the toxic ratio (TR). CYP activities of all cell lines were determined by using fluorescence-based assays. Only ARE-<i>bla</i> showed a low basal CYP activity and inducibility and AREc32 showed a low inducibility. Overall cytotoxicity was similar in all three assays despite the different metabolic activities indicating that chemical metabolism is not relevant for the cytotoxicity of the tested chemicals in these assays. Up to 28 chemicals showed specific cytotoxicity with TR > 10 in the bioassays, but baseline toxicity could explain the effects of the majority of the remaining chemicals. Seven chemicals showed TR < 0.1 indicating inaccurate physicochemical properties or experimental artifacts like chemical precipitation, volatilization, degradation, or other loss processes during the <i>in vitro</i> bioassay. The new baseline model can be used not only to identify specific cytotoxicity mechanisms but also to identify potential problems in the experimental performance or evaluation of the bioassay and thus improve the quality of the bioassay data.
Revealing Subtle Active Tectonic Deformation: Integrating Lidar, Photogrammetry, Field Mapping, and Geophysical Surveys to Assess the Late Quaternary Activity of the Sava Fault (Southern Alps, Slovenia)
2024-04-23

We applied an interdisciplinary approach to analyze the late Quaternary activity of the Sava Fault in the Slovenian Southern Alps. The Sava Fault is an active strike-slip fault, and part of the Periadriatic Fault System that accommodated the convergence of Adria and Europe. It is one of the longest faults in the Southern Alps. Using high-resolution digital elevation models from lidar and photogrammetric surveys, we were able to overcome the challenges of assessing fault activity in a region with intense surface processes, dense vegetation, and relatively low fault slip rates. By integrating remote sensing analysis, geomorphological mapping, structural geological investigations, and near-surface geophysics (electrical resistivity tomography and ground penetrating radar), we were able to find subtle geomorphological indicators, detect near-surface deformation, and show distributed surface deformation and a complex fault pattern. Using optically stimulated luminescence dating, we tentatively estimated a slip rate of 1.8 ± 0.4 mm/a for the last 27 ka, which exceeds previous estimates and suggests temporal variability in fault behavior. Our study highlights the importance of modern high-resolution remote sensing techniques and interdisciplinary approaches in detecting tectonic deformation in relatively low-strain rate environments with intense surface processes. We show that slip rates can vary significantly depending on the studied time window. This is a critical piece of information since slip rates are a key input parameter for seismic hazard studies.
Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma
2024-04-23

Abstract Anal squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). Response to standard chemoradiotherapy (CRT) varies considerably. A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. Patients with localized ASCC, treated with CRT at three different sites of the German Cancer Consortium (DKTK) were included. Patient cohorts for molecular analysis included baseline formalin fixed paraffin embedded biopsies for immunohistochemistry ( n = 130), baseline RNA sequencing ( n = 98), peripheral blood immune profiling ( n = 47), and serum cytokine measurement ( n = 35). Gene set enrichment analysis showed that pathways for IFNγ, IFNα, inflammatory response, TNFα signaling via NF-κB, and EMT were significantly enriched in poor responders (all p &lt; 0.001). Expression of interferon-induced transmembrane protein 1 (IFITM1), both on mRNA and protein levels, was associated with reduced Freedom from locoregional failure (FFLF, p = 0.037) and freedom from distant metastasis (FFDM, p = 0.014). An increase of PD-L1 expression on CD4+ T-cells ( p &lt; 0.001) and an increase in HLA-DR expression on T-cells ( p &lt; 0.001) was observed in the peripheral blood after CRT. Elevated levels of regulatory T-cells and CXCL2 were associated with reduced FFLF ( p = 0.0044 and p = 0.004, respectively). Inflammatory pathways in tissue in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood are associated with resistance to CRT. To counteract this resistance mechanism, the RADIANCE randomized phase-2 trial currently tests the addition of the immune checkpoint inhibitor durvalumab to standard CRT in locally advanced ASCC.
Divergent Age-Dependent Conformational Rearrangement within Aβ Amyloid Deposits in APP23, APPPS1, and AppNL-F Mice
2024-04-23

Amyloid plaques composed of fibrils of misfolded Aβ peptides are pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of Aβ fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how Aβ fibril structures in situ differ in Aβ plaque of different mouse models expressing familial mutations in the AβPP gene. We imaged frozen brains with a combination of conformation-sensitive luminescent conjugated oligothiophene (LCO) ligands and Aβ-specific antibodies. LCO fluorescence mapping revealed that mouse models APP23, APPPS1, and <i>App</i><sup><i>NL-F</i></sup> have different fibril structures within Aβ-amyloid plaques depending on the AβPP-processing genotype. Co-staining with Aβ-specific antibodies showed that individual plaques from APP23 mice expressing AβPP Swedish mutation have two distinct fibril polymorph regions of core and corona. The plaque core is predominantly composed of compact Aβ40 fibrils, and the corona region is dominated by diffusely packed Aβ40 fibrils. Conversely, the AβPP knock-in mouse <i>App</i><sup><i>NL-F</i></sup>, expressing the AβPP Iberian mutation along with Swedish mutation has tiny, cored plaques consisting mainly of compact Aβ42 fibrils, vastly different from APP23 even at elevated age up to 21 months. Age-dependent polymorph rearrangement of plaque cores observed for APP23 and APPPS1 mice >12 months, appears strongly promoted by Aβ40 and was hence minuscule in <i>App</i><sup><i>NL-F</i></sup>. These structural studies of amyloid plaques in situ can map disease-relevant fibril polymorph distributions to guide the design of diagnostic and therapeutic molecules.
Genome-scale model of Rothia mucilaginosa predicts gene essentialities and reveals metabolic capabilities
2024-04-23

ABSTRACT Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick mucosal fluids. This environment facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may positively impact the disease. Rothia mucilaginosa , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled its anti-inflammatory properties using in vitro three-dimensional lung epithelial cell cultures and in vivo mouse models relevant to chronic lung diseases. Apart from this, R. mucilaginosa has been associated with severe infections. However, its metabolic capabilities and genotype-phenotype relationships remain largely unknown. To gain insights into its cellular metabolism and genetic content, we developed the first manually curated genome-scale metabolic model, i RM23NL. Through growth kinetics and high-throughput phenotypic microarray testings, we defined its complete catabolic phenome. Subsequently, we assessed the model’s effectiveness in accurately predicting growth behaviors and utilizing multiple substrates. We used constraint-based modeling techniques to formulate novel hypotheses that could expedite the development of antimicrobial strategies. More specifically, we detected putative essential genes and assessed their effect on metabolism under varying nutritional conditions. These predictions could offer novel potential antimicrobial targets without laborious large-scale screening of knockouts and mutant transposon libraries. Overall, i RM23NL demonstrates a solid capability to predict cellular phenotypes and holds immense potential as a valuable resource for accurate predictions in advancing antimicrobial therapies. Moreover, it can guide metabolic engineering to tailor R. mucilaginosa ’s metabolism for desired performance. IMPORTANCE Cystic fibrosis (CF) is a genetic disorder characterized by thick mucosal secretions, leading to chronic lung infections. Rothia mucilaginosa is a common bacterium found in various parts of the human body, acting as a normal part of the flora. In people with weakened immune systems, it can become an opportunistic pathogen, while it is prevalent and active in CF airways. Recent studies have highlighted its anti-inflammatory properties in the lower pulmonary system, indicating the intricate relationship between microbes and human health. Herein, we have developed the first manually curated metabolic model of R. mucilaginosa . Our study examined the previously unknown relationships between the bacterium’s genotype and phenotype and identified essential genes that impact the metabolism under various conditions. With this, we opt for paving the way for developing new strategies in antimicrobial therapy and metabolic engineering, leading to enhanced therapeutic outcomes in cystic fibrosis and related conditions.