julilili42/papers huggingface dataset:
Low literacy skills in adults can be largely explained by basic linguistic and domain-general predictors
2024-09-04

Introduction Despite having sufficient formal education, a large group of people cannot complete everyday tasks like reading, writing, or making basic calculations. Regarding reading, millions of people are not able to understand more complex texts despite the ability to read simple words or sentences; they have low literacy skills. Even though this problem has been known for decades, the causes and predictors of their poor reading comprehension skills are not fully explored. Socioeconomic, sociodemographic, and reading-related (i.e., linguistic) factors, especially of English-speaking participants and thus users of an opaque orthography, were often assessed. The goal of this study was to examine which linguistic, domain-general, or numerical factors predict substandard complex text reading as the core symptom of low literacy skills in adulthood. Methods To this end, we assessed a group of German-speaking participants—users of a transparent orthography—who are at risk for complex text reading deficits. Results The results indicated that linguistic variables (reduced word/pseudoword reading, weaker oral semantic and grammatical comprehension), working memory, and age predicted lower performance in text comprehension. This model explained 73% of the total variance, indicating that most of the deficits in complex text reading can be explained by a group of basic underlying linguistic and domain-general factors. Discussion We conclude that interventions for adults with low literacy skills and others at risk for complex text reading deficits should address word/pseudoword reading and focus on both written and oral comprehension.
Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis
2024-09-05

Abstract Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.
Abstract B029: Studies in human bone cell co-cultures reveal a potential mechanism underlying bone fractures in children treated with entrectinib and suggest a positive association with vitamin D
2024-09-05

Abstract Introduction: Entrectinib, a NTRK, ROS1 and ALK inhibitor, approved in the US for adult patients with ROS1-positive metastatic non-small cell lung cancer and adult and pediatric patients older than 1 month of age with solid tumors that have a NTRK gene fusion, has been associated with the occurrence of bone fractures, particularly in pediatric patients. These fractures might be caused by an inhibition of signaling pathways relevant for bone development in children. Methods: To investigate the mechanism of the observed effect we used a suite of human bone cells representing both juvenile and adult bone physiology. These models were treated with Entrectinib and its major metabolite M5. Molecular as well as functional readouts were assessed to reveal the pathomechanism of the observed clinical findings. Results: Data showed, that Entrectinib induced a reduction of cellular markers of osteoblastic activity and a reduced formation of mineralized matrix. Conversely, Entrectinib had stimulating effects on osteoclast function indicative of bone resorption. 3D osteoblast-osteoclast cultures revealed decreased stiffness after Entrectinib treatment, confirming the cell signaling data. These findings were particularly pronounced in the absence of 17β-estradiol, characteristic for juvenile bone. Finally, pre-treatment with Vitamin D led to partially restored osteoblast function in vitro, while osteoclast function was suppressed. Conclusions: These experiments support the suspected on-target effect of Entrectinib underlying increased fractures in children with developing bone, offering potential mitigation strategies once these observations have been confirmed with clinical data. Citation Format: Sabrina Ehnert, Kevin A. Schulz, Alison K. Cardenas, Georgina Meneses-Lorente, Adrian Roth, Sabine Fürst-Recktenwald. Studies in human bone cell co-cultures reveal a potential mechanism underlying bone fractures in children treated with entrectinib and suggest a positive association with vitamin D [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B029.
Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky
2024-09-05

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While many studies have investigated how color information is processed in visual brain areas of primate species, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of ‘predatory’-like dark UV-objects in noisy daylight scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species.
Continental-scale associations of Arabidopsis thaliana phyllosphere members with host genotype and drought
2024-09-06

Abstract Plants are colonized by distinct pathogenic and commensal microbiomes across different regions of the globe, but the factors driving their geographic variation are largely unknown. Here, using 16S ribosomal DNA and shotgun sequencing, we characterized the associations of the Arabidopsis thaliana leaf microbiome with host genetics and climate variables from 267 populations in the species’ native range across Europe. Comparing the distribution of the 575 major bacterial amplicon variants (phylotypes), we discovered that microbiome composition in A. thaliana segregates along a latitudinal gradient. The latitudinal clines in microbiome composition are predicted by metrics of drought, but also by the spatial genetics of the host. To validate the relative effects of drought and host genotype we conducted a common garden field study, finding 10% of the core bacteria to be affected directly by drought and 20% to be affected by host genetic associations with drought. These data provide a valuable resource for the plant microbiome field, with the identified associations suggesting that drought can directly and indirectly shape genetic variation in A. thaliana via the leaf microbiome.
Time for an Update
2024-09-06

Abstract: Scientific evidence for many effects tends to be ambiguous. Here we investigated how psychological novices update their preexisting beliefs about psychological effects based on ambiguous scientific evidence. Specifically, we investigated various predictors and systematic patterns of belief updating. Participants were presented a series of fictitious hypotheses, accompanied by a series of fictitious study outcomes. For each hypothesis, we assessed participants’ preexisting beliefs and subjective expertise regarding the topic, as well as their posterior beliefs after presentation of scientific evidence. We found a negative effect of subjective expertise and positive effects of trust in psychological science and number of studies investigating an effect on belief updating. We further found evidence for a belief updating pattern according to which participants weight the outcome of the most recent study stronger than that of previous studies. The results advance our understanding of evidence-based belief updating and provide practical implications for science communication.
Made by the Hands of God: Human Dignity in Hilary of Poitiers’s Exegesis of Ps 118:73a LXX
2024-09-06

Abstract In his commentary on Psalm 118( LXX ):73a, “Your hands made me and fashioned me” (Tract.118Ps. 10.1–8), Hilary of Poitiers provides a unique perspective on the creation of humanity and on its exceptional dignity. I will examine key aspects of Hilary’s exegesis of this verse, namely, the identification of the hands of God, the interpretation of the two verbs “made” and “fashioned”, and the connections with Genesis 1:26 and 2:7. I will also compare Hilary’s interpretation of Ps 118:73a to the views expressed by other authors such as Theophilus, Irenaeus, Origen, Tertullian, Ambrose, and Didymus, with the purpose of contextualising Hilary’s novel understanding of human dignity within the larger framework of Early Christian interpretations of Genesis.
Ensemble surrogate modeling of advective-dispersive transport with intraparticle diffusion model for column-leaching test
2024-09-07

Column-leaching tests are a common approach for assessing the leaching behavior and resulting environmental risks of contaminated soils and waste materials, which are frequently reused for various construction purposes. The observed breakthrough curves of the contaminants are influenced by the complex dynamics of solute transport and kinetic inter-phase mass transfer. Disentangling these interactions necessitates numerical models. However, inverse modeling and sensitivity analysis can be time-consuming, especially when sorption kinetics are explicitly described by intraparticle diffusion, which requires discretizing the domain both in the flow direction along the column axis and inside the grains. To circumvent the need for such computationally intensive models, we have developed two different ensemble surrogate models. These models employ two separate ensemble methods: random forest stacking and inverse-distance weighted interpolation. Each method is applied to base surrogate models that cover different parts of the parameter space. The base surrogate models use the method of Extremely randomized Trees (ExtraTrees). The defined parameter range is based on the German standard for column-leaching tests. To optimize the base surrogate models, we utilized adaptive-sampling methods based on three distinct infill criteria: maximizing the expected improvement, staying within a certain Mahalanobis distance to the best estimate (both for exploitation), and maximizing the standard deviation (for exploration). The ensemble surrogate model demonstrates excellent performance in emulating the behavior of the original numerical model, with a relative root mean squared error of 0.09. We applied our proposed ensemble surrogate model to estimate the complete posterior parameter distribution using Simulation-Based Inference, specifically Neural Posterior Estimation, to determine the full parameter distribution conditioned on copper-leaching data from two different soils. Samples drawn from the posterior distribution align perfectly with the observed data for both the surrogate and original models.
EyeMatics: An Ophthalmology Use Case Within the German Medical Informatics Initiative
2024-09-07

Abstract The EyeMatics project, embedded as a clinical use case in Germany’s Medical Informatics Initiative, is a large digital health initiative in ophthalmology. The objective is to improve the understanding of the treatment effects of intravitreal injections, the most frequent procedure to treat eye diseases. To achieve this, valuable patient data will be meaningfully integrated and visualized from different IT systems and hospital sites. EyeMatics emphasizes a governance framework that actively involves patient representatives, strictly implements interoperability standards, and employs artificial intelligence methods to extract biomarkers from tabular and clinical data as well as raw retinal scans. In this perspective paper, we delineate the strategies for user-centered implementation and health care–based evaluation in a multisite observational technology study.
Benchmarking whole exome sequencing in the German network for personalized medicine
2024-09-08

INTRODUCTION: Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis. METHODS: To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics. Somatic and germline variants, copy-number alterations (CNAs), and complex biomarkers were investigated. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. The raw data were collected and re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability. RESULTS: The mean positive percentage agreement (PPA) of somatic variant calling was 76 % while the positive predictive value (PPV) was 89 % in relation to a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88 % for all and 97 % for the clinically relevant variants. CNA calls were concordant for 82 % of genomic regions. Homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94 %, 93 %, and 93 % of calls, respectively. Variability of CNAs and complex biomarkers did not decrease considerably after harmonization of the bioinformatic processing and was hence attributed mainly to wet-lab differences. CONCLUSION: Continuous optimization of bioinformatic workflows and participating in round robin tests are recommended.
Characterizing Mechanical Changes in the Biceps Brachii Muscle in Mild Facioscapulohumeral Muscular Dystrophy Using Shear Wave Elastography
2024-09-08

There is no general consensus on evaluating disease progression in facioscapulohumeral muscular dystrophy (FSHD). Recently, shear wave elastography (SWE) has been proposed as a noninvasive diagnostic tool to assess muscle stiffness in vivo. Therefore, this study aimed to characterize biceps brachii (BB) muscle mechanics in mild-FSHD patients using SWE. Eight patients with mild FSHD, the BB were assessed using SWE, surface electromyography (sEMG), elbow moment measurements during rest, maximum voluntary contraction (MVC), and isometric ramp contractions at 25%, 50%, and 75% MVC across five elbow positions (60°, 90°, 120°, 150°, and 180° flexion). The mean absolute percentage deviation (MAPD) was analyzed as a measure of force control during ramp contractions. The shear elastic modulus of the BB in FSHD patients increased from flexed to extended elbow positions (e.g., p &lt; 0.001 at 25% MVC) and with increasing contraction intensity (e.g., p &lt; 0.001 at 60°). MAPD was highly variable, indicating significant deviation from target values during ramp contractions. SWE in mild FSHD is influenced by contraction level and joint angle, similar to findings of previous studies in healthy subjects. Moreover, altered force control could relate to the subjective muscle weakness reported by patients with dystrophies.
Quantum Effects Explain the Twist Angle in the Helical Structure of DNA
2024-09-09

Abstract Why are DNA bases stacked in a double helix structure? We combined three theoretical approaches to demonstrate how one core concept derived from quantum mechanics (Pauli repulsion) annihilates the contribution of dispersion to the π–π stacking. The helical architecture is governed by a combination of exchange and electrostatic forces, a result that is interpreted from both a computational and a biological perspective.
Cerebrovascular Reactivity Assessed by Breath-Hold Functional MRI in Patients with Neurological Post-COVID-19 Syndrome—A Pilot Study
2024-09-09

Endothelial dysfunction represents a potential pathomechanism of neurological post-COVID-19 syndrome (PCS). A recent study demonstrated reduced cerebrovascular reactivity (CVR) in patients with PCS. The aim of this pilot study was to prospectively assess CVR in patients with PCS using breath-hold functional MRI (bh-fMRI). Fourteen patients with neurological PCS and leading symptoms of fatigue/memory issues/concentration disorder (PCSfmc), 11 patients with PCS and leading symptoms of myopathy/neuropathy (PCSmn), and 17 healthy controls underwent bh-fMRI. Signal change and time to peak (TTP) were assessed globally and in seven regions of interest and compared between the subgroups using one-way ANCOVA adjusting for age, time since infection, Fazekas score, and sex. No significant differences were observed. In PCS patients, the global CVR exhibited a slight, non-significant tendency to be lower compared to healthy controls (PCSfmc: 0.78 ± 0.11%, PCSmn: 0.84 ± 0.10% and 0.87 ± 0.07%). There was a non-significant trend towards lower global TTP values in the PCS subgroups than in the control group (PCSfmc: 26.41 ± 1.39 s, PCSmn: 26.32 ± 1.36 s versus 29.52 ± 0.93 s). Endothelial dysfunction does not seem to be the sole pathomechanism of neurological symptoms in PCS. Further studies in larger cohorts are required.
GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)
2024-09-10

Abstract Background Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA. Methods GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson’s disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores). Results In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90–1.00; plasma: AUC = 0.90, 95% CI 0.81–1.00). Discussion In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.
Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy
2024-09-10

Aim: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). Patients–methods: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. Results: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p &lt; 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p &lt; 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p &lt; 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p &lt; 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p &lt; 0.001, 0.025, 0.009, and &lt;0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. Conclusions: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.