julilili42/papers huggingface dataset:
Direct fluorescent labeling of NF186 and NaV1.6 in living primary neurons using bioorthogonal click chemistry
2023-06-08

ABSTRACT The axon initial segment (AIS) is a highly specialized neuronal compartment that regulates the generation of action potentials and maintenance of neuronal polarity. Live imaging of the AIS is challenging due to the limited number of suitable labeling methods. To overcome this limitation, we established a novel approach for live labeling of the AIS using unnatural amino acids (UAAs) and click chemistry. The small size of UAAs and the possibility of introducing them virtually anywhere into target proteins make this method particularly suitable for labeling of complex and spatially restricted proteins. Using this approach, we labeled two large AIS components, the 186 kDa isoform of neurofascin (NF186; encoded by Nfasc) and the 260 kDa voltage-gated Na+ channel (NaV1.6, encoded by Scn8a) in primary neurons and performed conventional and super-resolution microscopy. We also studied the localization of epilepsy-causing NaV1.6 variants with a loss-of-function effect. Finally, to improve the efficiency of UAA incorporation, we developed adeno-associated viral (AAV) vectors for click labeling in neurons, an achievement that could be transferred to more complex systems such as organotypic slice cultures, organoids, and animal models.
Bayesian penalty methods for evaluating measurement invariance in moderated nonlinear factor analysis.
2023-06-08

Measurement invariance (MI) is one of the main psychometric requirements for analyses that focus on potentially heterogeneous populations. MI allows researchers to compare latent factor scores across persons from different subgroups, whereas if a measure is not invariant across all items and persons then such comparisons may be misleading. If full MI does not hold further testing may identify problematic items showing differential item functioning (DIF). Most methods developed to test DIF focused on simple scenarios often with comparisons across two groups. In practical applications, this is an oversimplification if many grouping variables (e.g., gender, race) or continuous covariates (e.g., age) exist that might influence the measurement properties of items; these variables are often correlated, making traditional tests that consider each variable separately less useful. Here, we propose the application of Bayesian Moderated Nonlinear Factor Analysis to overcome limitations of traditional approaches to detect DIF. We investigate how modern Bayesian shrinkage priors can be used to identify DIF items in situations with many groups and continuous covariates. We compare the performance of lasso-type, spike-and-slab, and global-local shrinkage priors (e.g., horseshoe) to standard normal and small variance priors. Results indicate that spike-and-slab and lasso priors outperform the other priors. Horseshoe priors provide slightly lower power compared to lasso and spike-and-slab priors. Small variance priors result in very low power to detect DIF with sample sizes below 800, and normal priors may produce severely inflated type I error rates. We illustrate the approach with data from the PISA 2018 study. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
A time slice analysis of dentistry students’ visual search strategies and pupil dilation during diagnosing radiographs
2023-06-08

Diagnosing orthopantomograms (OPTs: panoramic radiographs) is an essential skill dentistry students acquire during university training. While prior research described experts’ visual search behavior in radiology as global-to-focal for chest radiographs and mammography, generalizability to a hybrid search task in OPTs (i.e., searching for multiple, diverse anomalies) remains unclear. Addressing this gap, this study investigated visual search of N = 107 dentistry students while they were diagnosing anomalies in OPTs. Following a global-to-focal expert model, we hypothesized that students would use many, short fixations representing global search in earlier stages, and few, long fixations representing focal search in later stages. Furthermore, pupil dilation and mean fixation duration served as cognitive load measures. We hypothesized that later stages would be characterized by elaboration and a reflective search strategy, leading to higher cognitive load being associated with higher diagnostic performance in late compared to earlier stages. In line with the first hypothesis, students’ visual search comprised of a three-stage process that grew increasingly focal in terms of the number of fixations and anomalies fixated. Contrary to the second hypothesis, mean fixation duration during anomaly fixations was positively associated with diagnostic performance across all stages. As OPTs greatly varied in how difficult it was to identify the anomalies contained therein, OPTs with above-average difficulty were sampled for exploratory analysis. Pupil dilation predicted diagnostic performance for difficult OPTs, possibly capturing elaborative cognitive processes and cognitive load compared to mean fixation duration. A visual analysis of fine-grained time slices indicated large cognitive load differences towards the end of trials, showcasing a richness-resolution-trade-off in data sampling crucial for future studies using time-slicing of eye tracking data.
BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis
2023-06-09

Abstract Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, is characterized by an aggressive clinical course. In approximately one-third of patients with DLBCL, first-line multiagent immunochemotherapy fails to produce a durable response. Molecular heterogeneity and apoptosis resistance pose major therapeutic challenges in DLBCL treatment. To circumvent apoptosis resistance, the induction of ferroptosis might represent a promising strategy for lymphoma therapy. In this study, a compound library, targeting epigenetic modulators, was screened to identify ferroptosis-sensitizing drugs. Strikingly, bromodomain and extra-terminal domain (BET) inhibitors sensitized cells of the germinal center B-cell–like (GCB) subtype of DLBCL to ferroptosis induction and the combination of BET inhibitors with ferroptosis inducers, such as dimethyl fumarate or RSL3, synergized in the killing of DLBCL cells in vitro and in vivo. On the molecular level, the BET protein BRD4 was found to be an essential regulator of ferroptosis suppressor protein 1 expression and thus to protect GCB-DLBCL cells from ferroptosis. Collectively, we identified and characterized BRD4 as an important player in ferroptosis suppression in GCB-DLBCL and provide a rationale for the combination of BET inhibitors with ferroptosis-inducing agents as a novel therapeutic approach for DLBCL treatment.
Long-term prognostic factors for PRRT in neuroendocrine tumors
2023-06-09

Aim/introduction Peptide receptor radionuclide therapy (PRRT) is an effective and well-tolerated treatment option for patients with neuroendocrine tumors (NETs) that prolongs progression-free survival (PFS). However, the limited overall survival (OS) rates in the prospective phase III study (NETTER1) highlighted the need to identify patient-specific long-term prognostic markers to avoid unnecessary side effects and enable better treatment stratification. Therefore, we retrospectively analyzed prognostic risk factors in NET patients treated with PRRT. Methods A total of 62 NET patients (G1: 33.9%, G2 62.9%, and G3 3.2%) with at least 2 cycles of PRRT with [ 177 Lu]Lu-HA-DOTATATE (mean 4 cycles) were analyzed. Of which, 53 patients had primary tumors in the gastroenteropancreatic (GEP) system, 6 had bronchopulmonary NET, and 3 had NET of unknown origin. [ 68 Ga]Ga-HA-DOTATATE PET/CT scans were performed before PRRT start and after the second treatment cycle. Different clinical laboratory parameters, as well as PET parameters, such as SUVmean, SUVmax, and PET-based molecular tumor volume (MTV), were collected, and their impact on the OS was investigated. Patient data with a mean follow-up of 62 months (range 20–105) were analyzed. Results According to interim PET/CT, 16 patients (25.8%) presented with partial response (PR), 38 (61.2%) with stable disease (SD), and 7 (11.3%) with progressive disease (PD). The 5-year OS was 61.8% for all patients, while bronchopulmonary NETs showed poorer OS than GEP-NETs. Multivariable Cox regression analysis showed that chromogranin A level and MTV together were highly significant predictors of therapeutic outcome (HR 2.67; 95% CI 1.41–4.91; p = 0.002). Treatment response was also influenced by the LDH level (HR 0.98; 95% CI 0.9–1.0; p = 0.007) and patient age (HR 1.15; 95% CI 1.08–1.23; p &amp;lt; 0.001). ROC analysis revealed baseline MTV &amp;gt; 112.5 ml [Sens. 91%; Spec. 50%; AUC 0.67 (95% CI 0.51–0.84, p = 0.043)] and chromogranin A &amp;gt;1,250.75 μg/l [Sens. 87%; Spec. 56%; AUC 0.73 (95% CI 0.57–0.88, p = 0.009)] as the best cutoff values for identifying patients with worse 5-year survival. Conclusion Our retrospective analysis defined MTV and chromogranin A in combination as significant prognostic factors for long-term OS. Furthermore, an interim PET/CT after two cycles has the potential in identifying non-responders who may benefit from a change in therapy at an early stage.
Optical solitons in curved spacetime
2023-06-09

Abstract Light propagation in curved spacetime is at the basis of some of the most stringent tests of Einstein’s general relativity. At the same time, light propagation in media is at the basis of several communication systems. Given the ubiquity of the gravitational field, and the exquisite level of sensitivity of optical measurements, the time is ripe for investigations combining these two aspects and studying light propagation in media located in curved spacetime. In this work, we focus on the effect of a weak gravitational field on the propagation of optical solitons in non-linear optical media. We derive a non-linear Schrödinger equation describing the propagation of an optical pulse in an effective, gradient-index medium in flat spacetime, encoding both the material properties and curved spacetime effects. In analyzing the special case of propagation in a 1D optical fiber, we also include the effect of mechanical deformations and show it to be the dominant effect for a fiber oriented in the radial direction in Schwarzschild spacetime.
WebLicht-Batch -- A Web-Based Interface for Batch Processing Large Input with the WebLicht Workflow Engine
2023-06-09

WebLicht is a workflow engine that gives researchers access to a well-inhabited space of natural language processing tools that can be combined into tool chains to perform complex natural language analyses. In this paper, we present WebLicht-Batch, a web-based interface to WebLicht's chainer back-end. WebLicht-Batch helps users to automatically feed large input data, or input data of multiple files into WebLicht. It disassembles large input into smaller, more digestible sizes, feeds the resulting parts into WebLicht's pipelining and execution engine, and then assembles the results of such processing into files that preserve the usual input-output dichotomy.
KCNC2 variants of uncertain significance are also associated to various forms of epilepsy
2023-06-09

Recently, de novo variants in KCNC2 , coding for the potassium channel subunit K V 3.2, have been described as causative for various forms of epilepsy including genetic generalized epilepsy (GGE) and developmental and epileptic encephalopathy (DEE). Here, we report the functional characteristics of three additional KCNC2 variants of uncertain significance and one variant classified as pathogenic. Electrophysiological studies were performed in Xenopus laevis oocytes. The data presented here support that KCNC2 variants with uncertain significance may also be causative for various forms of epilepsy, as they show changes in the current amplitude and activation and deactivation kinetics of the channel, depending on the variant. In addition, we investigated the effect of valproic acid on K V 3.2, as several patients carrying pathogenic variants in the KCNC2 gene achieved significant seizure reduction or seizure freedom with this drug. However, in our electrophysiological investigations, no change on the behavior of K V 3.2 channels could be observed, suggesting that the therapeutic effect of VPA may be explained by other mechanisms.
The transnational prosocial activities of elite African footballers in their communities of origin
2023-06-09

Through a digital ethnography of Twitter and Instagram and semi-structured interviews, this paper examined the different forms of prosocial activities of elite African footballers in their home countries. A few studies have examined 'give back' activities in communities of origin in the form of remittances to family and friends and social philanthropy initiatives. This approach has proven to be limited as it does not capture their non-material contributions to society. By framing the research problem around the concepts of prosocial behaviour and athlete citizenship, this study added new dimensions to our understanding of African players' prosocial activities in their home countries. The findings show that African players are socially conscious agents who are obliged by their social norms and cultural values to support their communities in many different ways, including through active citizenship. The implication is that conceptions of the elite African athlete need to recognise them as 'citizen athletes' whose non-sporting lives go beyond remittances and philanthropy.
Metric information in cognitive maps: Euclidean embedding of non-Euclidean environments
2023-06-09

Abstract The structure of the internal representation of surrounding space, the so-called cognitive map , has long been debated. A Euclidean metric map is the most straight-forward hypothesis, but human navigation has been shown to systematically deviate from the Euclidean ground truth. Vector navigation based on non-metric models can better explain the observed behavior, but also discards useful geometric properties such as fast shortcut estimation and cue integration. Here, we propose another alternative, a Euclidean metric map that is systematically distorted to account for the observed behavior. The map is found by embedding the non-metric model, a labeled graph, into 2D Euclidean coordinates. We compared these two models using human data from Warren et al. (2017), where participants had to navigate and learn a non-Euclidean maze (i.e., with Wormholes) and perform direct shortcuts between different locations. Even though the Euclidean embedding cannot correctly represent the non-Euclidean environment, both models predicted the data equally well. We argue that the so embedded graph naturally arises from integrating the local position information into a metric framework, which makes the model more powerful and robust than the non-metric alternative. It may therefore be a better model for the human cognitive map.
Dataset for Jiao et al., 2023.xlsx
2023-06-09

Dataset from Jiao, W., Wan, S., Li, Y., Zhao, D., Liu, C., Jin, H., et al. (2023). Global cooling-driven summer monsoon weakening in South China across the Eocene-Oligocene transition. <br> The dataset set includes two worksheets in the EXCEL. The first worksheet documents magnetic parameters and diffuse reflectance spectroscopy data. The second one documents the unmixing results of isothermal remanent magnetization acquisition curves.
Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFRkinase inhibitors
2023-06-09

&amp;lt;p&amp;gt;The attached archives contain Molecular Dynamics trajectories for both compound 1 and 2. Each archive encompasses 10 replicas of MD simulation for each ligand. The *_raw_interaction_data.zip includes the interactions derived from MD trajectories&amp;nbsp;in the *.dat format, separated for interaction components (i.e. Hydrophobic interactions/Hydrogen Bonding) for concatenated trajectories with the total length of 10&amp;mu;s/compound. The *_MMGBSA_raw_data_merged_trajectory.csv include the&amp;nbsp;full-component MM/GBSA tables&amp;nbsp;for concatenated trajectories with the total length of 10&amp;mu;s/compound.&amp;lt;/p&amp;gt;\\n\\n&amp;lt;p&amp;gt;&amp;nbsp;&amp;lt;/p&amp;gt;
Thy Kingdom Come? Visualizing (Post)Colonial Futures in the German Southwest
2023-06-09

The future of colonial pasts still haunts Christian imagination and theology. This is especially true in the field of eschatology, which is dedicated to Christian ways of conceiving the future. This article examines the manifold entanglements that collude in the fabrication of Christian imaginaries of time, future, and global community within (post)colonial conditions. At the center of the article resides the case study of a lithograph distributed by missionary networks in the second half of the 19th century and passed down over three generations in a German Swabian craftsman’s family. The first part of the article offers a detailed image analysis of the lithograph, paying special attention to its ways of religious and colonial worlding. The second examines the social milieu of the addressees of the lithograph and analyzes its embeddedness in intersectional webs of religious, aesthetic, and social disciplining. It draws attention to the complex, often ambiguous dynamics involved in producing colonial inferiority. Against this background, the third part explores, in the form of a provisional thought experiment, ways of a decolonial revision of the lithograph, which bring the aforementioned ambivalences “into view” and interrupt its temporal hierarchization.
Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort
2023-06-10

Language deficits exist in the prodromal but not asymptomatic stages of genetic FTD across all three genetic groups. Improved understanding of the language phenotype prior to phenoconversion to fully symptomatic FTD will help develop outcome measures for future presymptomatic trials.
Dataset on simulations of Kinetic of Fe(II) oxidation
2023-06-10

This upload contains simulation and fitting data matching figures in the publication "Kinetic constraints for the formation of microniches for microaerophilic Fe(II) oxidation”, Peiffer et al, submitted to GCA. It further contains the matlab code used for the simulations (micro_n_iteration_v1.m) <br>
A Structurally Flexible Halide Solid Electrolyte with High Ionic Conductivity and Air Processability
2023-06-11

Abstract In this work, a structurally revivable, chloride‐ion conducting solid electrolyte (SE), CsSn 0.9 In 0.067 Cl 3 , with a high ionic conductivity of 3.45 × 10 −4 S cm −1 at 25 °C is investigated. The impedance spectroscopy, density functional theory, solid‐state 35 Cl NMR, and electron paramagnetic resonance studies collectively reveal that the high Cl − ionic mobility originates in the flexibility of the structural building blocks, Sn/InCl 6 octahedra. The vacancy‐dominated Cl − ion diffusion encompasses co‐ordinated Sn/In(Cl) site displacements that depend on the exact stoichiometry, and are accompanied by changes in the local magnetic moments. Owing to these promising properties, the suitability of the CsSn 0.9 In 0.067 Cl 3 , as an electrolyte is demonstrated by designing all‐solid‐state batteries, with different anodes and cathodes. The comparative investigation of interphases with Li, Li–In, Mg, and Ca anodes reveals different levels of reactivity and interphase formation. The CsSn 0.9 In 0.067 Cl 3 demonstrates an excellent humidity tolerance (up to 50% relative humidity) in ambient air, maintaining high structural integrity without compromises in ionic conductivity, which stands in contrast to commercial halide‐based lithium conductors. The discovery of a halide perovskite conductor, with air processability and structure revival ability paves the way for the development of advanced air processable SEs, for next‐generation batteries.
Sexual function in Chinese women with different clinical phenotypes of polycystic ovary syndrome
2023-06-11

<b>Objective:</b> To investigate sexual function stratified according to four clinical phenotypes of polycystic ovary syndrome (PCOS) and its association with clinical and quality of life parameters, and to compare these with healthy controls in Chinese women with PCOS. <b>Methods:</b> A cross-sectional study was designed in 1000 PCOS women and 500 control women aged 18-45 years. PCOS women were grouped into four clinical phenotypes according to the Rotterdam Criteria. FSFI (Female Sexual Function Index), SF-12 (the 12-item short form health survey) and clinical and hormonal characteristics likely to affect sexual function were determined. <b>Results:</b> 809 PCOS women and 385 control women with complete parameters were evaluated after screening. Phenotype A had a lower total FSFI mean score (23.14 ± 3.22) compared with phenotype D and control group (<i>p</i> < 0.05). The control group had the highest total FSFI mean score (24.98 ± 3.78). For the percentage at risk of sexual dysfunction, phenotype A (87.5%) and phenotype B (82.46%) had a higher risk of female sexual dysfunction (FSD) than that in phenotype C (75.34%), phenotype D (70.56%) and control group (61.30%) (<i>p</i> < 0.05). SF-12 mental domain scores were significantly lower in phenotypes A and B compared with phenotypes C and control group (<i>p</i> < 0.05). Infertility treatment, bioavailable testosterone, psychological factors, age and waist circumference presented negative correlation with female sexual function. <b>Conclusions:</b> The risk of FSD in PCOS women seemed to be associated with PCOS clinical phenotypes. The classical PCOS phenotype with oligo-ovulation and hyperandrogenism had a higher risk of sexual dysfunction.
Neuropathy target esterase activity predicts retinopathy amongPNPLA6disorders
2023-06-11

Abstract Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. PNPLA6 encodes Neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a clinical meta-analysis of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 10 variants as likely pathogenic and 36 variants as pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship and the generation of a preclinical animal model pave the way for therapeutic trials, using NTE as a biomarker.