julilili42/papers huggingface dataset:
A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides
2024-02-22

The marine sponge-derived fungus <i>Stachylidium bicolor</i> 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid <i>N</i>-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (<b>1</b>) and F (<b>2</b>). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V<sub>1A</sub> receptor, a member of the G protein-coupled receptor superfamily.
ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations
2024-02-22

Abstract Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10−/− mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.
Modifying biased attention towards food stimuli in binge eating disorder: A multi-session training study
2024-02-22

Individuals with binge eating disorder (BED) exhibit a biased attention towards food stimuli. Against this backdrop, the present study with pre-registered design (ID: DRKS00012984) tested whether (a) a training designed to reduce attentional food processing indeed modifies this bias, (b) this reduction is evident in several measures of food-related attention and (c) this is associated with reductions in craving, binge frequency over the past 28 days and calories eaten in a laboratory based bogus taste test. Individuals with BED were randomly allocated to four sessions of either an attentional bias modification training (ABMT; n = 39) or a comparable no-modification control training (CT; n = 27). In all measures assessed via eye-tracking - dwell time bias, dwell time bias variability and first fixation bias - food-related bias decreased in the ABMT relative to the CT. Against our hypothesis, no differential between-group effects were found for reaction time (RT) bias and its variability as well as for calories consumed in a bogus taste test. By contrast, reductions in binge frequency and subjective craving were found for both groups. Taken together, the tendency to preferentially process food seems a modifiable phenomenon in individuals with BED. However, modifying this selective viewing pattern does not seem a prerequisite for a successful reduction of binge frequency.
Indocyanine Green Angiography
2024-02-22

The choroid plays an important role in the pathophysiology of the eye. Multimodal imaging offers different techniques to examine the choroid. Fundus fluorescein angiography offers limited visualization of the deep layers of the fundus due to the barrier property of the retinal pigment epithelium. Therefore, indocyanine green angiography (ICGA) is widely used in the angiographic examination of the choroidal structure. ICGA is an important component of multimodal imaging in the diagnosis and treatment of many degenerative, tumoral, and inflammatory diseases of the choroid and retina. This review presents the general characteristics of ICGA and a practical approach to its clinical use.
Variability in geochemical weathering indices in loess over the last full glacial cycle at Karamaidan, central Asia (Tajikistan)
2024-02-22

This study presents the first quantitative assessment of weathering conditions in the Tajikistan depression throughout the last full glacial cycle. We employed geochemical and magnetic susceptibility analyses to investigate various weathering indices (WIs), with the CPA and FENG indices identified as the most suitable for this region. Our results confirm the formation of a robust pedocomplex, PS2, during the OIS5 interglacial phase, while primary loess deposition occurred during the interstadials. The presence of a weak paleosol, PS1, suggests that OIS3 was not significantly pronounced, and sediment transport and deposition continued during this period. Furthermore, we assessed the effectiveness of various climatic transfer functions, including some recently developed specifically for Chinese loess. These transfer functions have also shown promising applicability to the loess of Central Asia, producing realistic climate trends that are, however, still to be taken with caution. The MAT and mean annual precipitation generated with these functions show for the last interglacial period about 13°C and 665 mm, thus higher temperatures and lower precipitation than the current conditions of 10.8°C and 730 mm. These results indicate a significant increase (c. 15%) in both temperature and precipitation compared to the stadial periods.
Enhancing r1 Relaxivity in GdDOTA-Monoamide Complexes through Polar Group-Mediated Ordering of Second-Sphere Water Molecules
2024-02-22

This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r1 relaxivity from 3.0 to 6.3 mM–1 s–1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r1 with changes in pH, the unique r1 versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r1 is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid–base prototropic mechanisms.
Standardization of a CT Protocol for Imaging Patients with Suspected COVID-19—A RACOON Project
2024-02-22

CT protocols that diagnose COVID-19 vary in regard to the associated radiation exposure and the desired image quality (IQ). This study aims to evaluate CT protocols of hospitals participating in the RACOON (Radiological Cooperative Network) project, consolidating CT protocols to provide recommendations and strategies for future pandemics. In this retrospective study, CT acquisitions of COVID-19 patients scanned between March 2020 and October 2020 (RACOON phase 1) were included, and all non-contrast protocols were evaluated. For this purpose, CT protocol parameters, IQ ratings, radiation exposure (CTDIvol), and central patient diameters were sampled. Eventually, the data from 14 sites and 534 CT acquisitions were analyzed. IQ was rated good for 81% of the evaluated examinations. Motion, beam-hardening artefacts, or image noise were reasons for a suboptimal IQ. The tube potential ranged between 80 and 140 kVp, with the majority between 100 and 120 kVp. CTDIvol was 3.7 ± 3.4 mGy. Most healthcare facilities included did not have a specific non-contrast CT protocol. Furthermore, CT protocols for chest imaging varied in their settings and radiation exposure. In future, it will be necessary to make recommendations regarding the required IQ and protocol parameters for the majority of CT scanners to enable comparable IQ as well as radiation exposure for different sites but identical diagnostic questions.
Weak error analysis for the stochastic Allen–Cahn equation
2024-02-22

Abstract We prove strong rate resp. weak rate <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>O</mml:mi> <mml:mo>(</mml:mo> <mml:mi>τ</mml:mi> <mml:mo>)</mml:mo> </mml:mrow> </mml:math> for a structure preserving temporal discretization (with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>τ</mml:mi> </mml:math> the step size) of the stochastic Allen–Cahn equation with additive resp. multiplicative colored noise in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>d</mml:mi> <mml:mo>=</mml:mo> <mml:mn>1</mml:mn> <mml:mo>,</mml:mo> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mn>3</mml:mn> </mml:mrow> </mml:math> dimensions. Direct variational arguments exploit the one-sided Lipschitz property of the cubic nonlinearity in the first setting to settle first order strong rate. It is the same property which allows for uniform bounds for the derivatives of the solution of the related Kolmogorov equation, and then leads to weak rate <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>O</mml:mi> <mml:mo>(</mml:mo> <mml:mi>τ</mml:mi> <mml:mo>)</mml:mo> </mml:mrow> </mml:math> in the presence of multiplicative noise. Hence, we obtain twice the rate of convergence known for the strong error in the presence of multiplicative noise.
Gas Phase Ionization Energy of Heptacene
2024-02-22

The ionization energy is a fundamental property that is relevant to charge transport in organic semiconductors. We report adiabatic ionization energies (AIEs) of heptacene at 6.21 and 7.20 eV for the X̃<sup>+</sup>B<sub>2g</sub> and Ã<sup>+</sup>A<sub>u</sub> states, respectively, as the next larger member of the acene series using mass- and isomer-selective double imaging photoelectron photoion coincidence spectroscopy. The X̃<sup>+</sup> state energy decreases monotonically with an increase in size within the homologous series of acenes and approaches an asymptotic limit [AIE(polyacene) = 5.94 ± 0.06 eV] based on a fit with an exponential decay function. As byproducts of heptacene formation from cycloreversion of diheptacenes, 5,18-, 7,16-, and 6,17-dihydroheptacene can be detected, and their AIE is similar to that of their largest acene subunit (anthracene and tetracene, respectively), in very good agreement with computational treatments.
Short-term transfer effects of Tetris on mental rotation: Review and registered report — A Bayesian approach
2024-02-22

Abstract The existence of transfer effects of video games on cognitive performance are controversially discussed in experimental psychology. Whereas recent meta-analyses suggest the absence of far transfer effects, empirical evidence regarding near transfer effects is more controversial. This conceptual replication investigated the short-term near transfer effect of playing Tetris on mental rotation abilities. The design of the conceptual replication was based on a comprehensive compilation of the methods used by previous literature on this topic and advanced in order to reach a high scientific state-of-the-art standard. We ran a high-powered conceptual replication study with 366 participants randomly assigned to either an experimental group playing Tetris or a control group playing Solitaire. Both groups completed three commonly used mental rotation tests in a pre- and a posttest session. Additionally, the experimental group played Tetris while the control group played Solitaire. Playing time was 10 hours in total within 4 weeks. Based on previous research, we hypothesized that this might generate a short-term transfer effect of Tetris on mental rotation. While participants showed a repeated testing effect for the mental rotation tests in both groups, we found evidence that Tetris does not produce a short-term transfer effect on mental rotation. Both gender and expected outcomes did not influence this effect. Our study suggests that playing Tetris does not improve mental rotation skills.
Peri-Tetracene from 1,1′-Bitetracene: Zipping up Structurally Defined Graphene Nanoribbons
2024-02-22

Polycyclic aromatic hydrocarbons (PAHs) are promising molecules for a manifold of applications in organic electronics, spintronics, or energy storage devices. Among PAHs, particular attention has been focused on the synthesis and study of acenes and fused acenes, peri-acenes, allowing tuning of the highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) gap with the size of the conjugated system. As a starting point for the surface synthesis of larger PAHs, we synthesized a 1,1′-bitetracene for the first time. This precursor molecule consists of two tetracene units connected via the 1,1′-position with a torsion angle of 70°. The interface properties of the molecule before and after annealing on a Cu(111) surface are investigated. Using X-ray photoemission spectroscopy (XPS), angle-resolved photoelectron spectroscopy (ARPES), low-energy electron diffraction (LEED), and scanning-tunneling microscopy (STM), it is experimentally demonstrated that the tetracene units zip up with the help of heat forming peri-tetracene. These results and the exact adsorption geometry are in excellent agreement with calculations using density functional theory (DFT). Moreover, the calculations enable the identification of newly formed valence band states at the interface to Cu(111).
Enhancing pre-service teachers’ technological pedagogical content knowledge (TPACK): Utility-value interventions support knowledge integration
2024-02-23

For meaningful technology-enhanced teaching, teachers need to systematically integrate the basic components of content, pedagogical and technological knowledge. To motivationally foster knowledge integration, we tested the effectiveness of a utility-value intervention in two experiments (laboratory: N = 43, online: N = 115) within German pre-service teacher education. Teachers randomly either received the utility-intervention or not. Afterwards all teachers were asked to learn essential aspects on teaching mathematics with technologies using an online learning environment. We did not find an effect on learning and motivation. Epistemic network analyses revealed that the intervention group realized more integration processes than the control group.
Validation of artificial intelligence-based digital microscopy for automated detection of Schistosoma haematobium eggs in urine in Gabon
2024-02-23

Introduction Schistosomiasis is a significant public health concern, especially in Sub-Saharan Africa. Conventional microscopy is the standard diagnostic method in resource-limited settings, but with limitations, such as the need for expert microscopists. An automated digital microscope with artificial intelligence (Schistoscope), offers a potential solution. This field study aimed to validate the diagnostic performance of the Schistoscope for detecting and quantifying Schistosoma haematobium eggs in urine compared to conventional microscopy and to a composite reference standard (CRS) consisting of real-time PCR and the up-converting particle (UCP) lateral flow (LF) test for the detection of schistosome circulating anodic antigen (CAA). Methods Based on a non-inferiority concept, the Schistoscope was evaluated in two parts: study A, consisting of 339 freshly collected urine samples and study B, consisting of 798 fresh urine samples that were also banked as slides for analysis with the Schistoscope. In both studies, the Schistoscope, conventional microscopy, real-time PCR and UCP-LF CAA were performed and samples with all the diagnostic test results were included in the analysis. All diagnostic procedures were performed in a laboratory located in a rural area of Gabon, endemic for S . haematobium . Results In study A and B, the Schistoscope demonstrated a sensitivity of 83.1% and 96.3% compared to conventional microscopy, and 62.9% and 78.0% compared to the CRS. The sensitivity of conventional microscopy in study A and B compared to the CRS was 61.9% and 75.2%, respectively, comparable to the Schistoscope. The specificity of the Schistoscope in study A (78.8%) was significantly lower than that of conventional microscopy (96.4%) based on the CRS but comparable in study B (90.9% and 98.0%, respectively). Conclusion Overall, the performance of the Schistoscope was non-inferior to conventional microscopy with a comparable sensitivity, although the specificity varied. The Schistoscope shows promising diagnostic accuracy, particularly for samples with moderate to higher infection intensities as well as for banked sample slides, highlighting the potential for retrospective analysis in resource-limited settings. Trial registration NCT04505046 ClinicalTrials.gov.
Baseline Toxicity Model to Identify the Specific and Nonspecific Effects of Per- and Polyfluoroalkyl Substances in Cell-Based Bioassays
2024-02-23

High-throughput screening is a strategy to identify potential adverse outcome pathways (AOP) for thousands of per- and polyfluoroalkyl substances (PFAS) if the specific effects can be distinguished from nonspecific effects. We hypothesize that baseline toxicity may serve as a reference to determine the specificity of the cell responses. Baseline toxicity is the minimum (cyto)toxicity caused by the accumulation of chemicals in cell membranes, which disturbs their structure and function. A mass balance model linking the critical membrane concentration for baseline toxicity to nominal (i.e., dosed) concentrations of PFAS in cell-based bioassays yielded separate baseline toxicity prediction models for anionic and neutral PFAS, which were based on liposome-water distribution ratios as the sole model descriptors. The specificity of cell responses to 30 PFAS on six target effects (activation of peroxisome proliferator-activated receptor (PPAR) gamma, aryl hydrocarbon receptor, oxidative stress response, and neurotoxicity in own experiments, and literature data for activation of several PPARs and the estrogen receptor) were assessed by comparing effective concentrations to predicted baseline toxic concentrations. HFPO-DA, HFPO-DA-AS, and PFMOAA showed high specificity on PPARs, which provides information on key events in AOPs relevant to PFAS. However, PFAS were of low specificity in the other experimentally evaluated assays and others from the literature. Even if PFAS are not highly specific for certain defined targets but disturb many toxicity pathways with low potency, such effects are toxicologically relevant, especially for hydrophobic PFAS and because PFAS are highly persistent and cause chronic effects. This implicates a heightened need for the risk assessment of PFAS mixtures because nonspecific effects behave concentration-additive in mixtures.
Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease
2024-02-23

Abstract INTRODUCTION Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double‐blind phase 3 DIAN‐TU‐001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab. METHODS We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker. RESULTS LC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid‐no‐change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid‐reduction class exhibited reductions in the annual decline rates compared to the amyloid‐growth class across multiple biomarker, clinical, and cognitive outcomes. DISCUSSION LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials. Highlights We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker. Despite similar baseline characteristics, the amyloid‐reduction class exhibited remarkably better outcomes compared to the amyloid‐growth class across multiple measures. LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects.
Humans flexibly integrate social information despite interindividual differences in reward
2024-02-23

There has been much progress in understanding human social learning, including recent studies integrating social information into the reinforcement learning framework.Yet previous studies often assume identical payoffs between observer and demonstrator, overlooking the diversity of real-world interactions. We address this gap by introducing a socially correlated bandit task that accommodates payoff differences among participants, allowing for the study of social learning under more realistic conditions. Our novel Social Generalization (SG) model, tested through evolutionary simulations and two online experiments, outperforms existing models by incorporating social information into the generalization process, but treated as noisier than individual observations. Our findings suggest that human social learning is more flexible than previously believed, with the SG model indicating a potential resource-rational trade-off where social learning partially replaces individual exploration. This research highlights the flexibility of humans social learning, allowing us to integrate social information from others with different preferences, skills, or goals.