julilili42/papers huggingface dataset:
Wide-pore fully porous mixed-mode octyl/pyridyl-bonded silica material with pH-dependent surface charge reversal for high-performance hydrophobic charge-induction chromatography of proteins
2024-10-09

In an attempt to overcome silanophilic interactions like observed on popular reversed-phase butyl‐bonded silica stationary phases in protein HPLC, a mixed-mode stationary phase based on wide pore silica (3 μm, 300 Å) was prepared by co-immobilization of octyl and 2-pyridylethyl ligands. The surface modification was performed by a new approach using synthesized functional silatranes of the above ligands and prewetted silica. It allowed to generate a dense polymeric siloxane layer on the silica surface. Butyl-bonded silica and octyl/3-aminopropyl-bonded mixed-mode silica phases were prepared for comparison. The modified silicas were subsequently characterized by elemental analysis regarding ligand densities, by solid-state <sup>29</sup>Si and <sup>13</sup>C cross polarization/magic angle spinning nuclear magnetic resonance spectroscopy for confirming the surface-bonded structure, and by pH-dependent ζ-potential measurements via electrophoretic light scattering providing net surface charge information at distinct pH values. While the classical butyl‐bonded stationary phase revealed negative ζ-potential over the entire pH range investigated (pH 3.5-9.5) due to residual silanols and the mixed-mode octyl/3-aminopropyl-bonded silica positive ζ-potential over the entire pH range, pH-dependent charge reversal was observed at approximately pH 5.5 for the octyl/pyridyl-bonded stationary phase. Then, a test set of proteins differing in hydrophobicities and isoelectric points was employed to evaluate the retention characteristics of all three synthesized stationary phases over the pH range of 3 to 7.5 by acetonitrile-gradient elution reversed-phase HPLC. Under acidic conditions (pH 3) the mixed-mode phases octyl/pyridyl-silica and octyl/aminopropyl-silica showed reduced retention and improved peak shapes due to repulsive interactions preventing silanophilic interactions, while protein separations by their hydrophobicities were achieved (repulsive charge-assisted protein RPLC). Finally, the prepared novel mixed-mode octyl/pyridyl-bonded stationary phase was evaluated in hydrophobic charge induction chromatography mode for protein separation of the same test set. Instead of an organic modifier gradient, elution was enforced by a pH gradient from almost neutral to acidic pH at constant organic modifier content of 10 %. This chromatographic mode showed orthogonal retention characteristics and reversed elution order compared to above organic gradient RP-HPLC. In addition, significantly less organic solvent was used under these conditions, classifying it as a green protein LC technology.
Development of 3D printed microneedles of varied needle geometries and lengths, designed to improve the dermal delivery of topically applied psoriasis treatments
2024-10-10

The aim of this study was to investigate the impact of using microneedle patches in addition to topical therapy for the treatment of psoriasis. Using continuous liquid interface production (CLIP) 3D printing we manufactured round microneedle array patches (MAPs) with a diameter of 14 mm. Needle geometries were varied from square pyramidal, conical, and obelisk, with varied needle lengths of 400 μm, 600 μm, 800 μm, or 1000 μm. MAPs were characterized for force to fracture, skin penetration, skin damage, as well as their ability to deliver a novel oleogel-based corticosteroid (betamethasone dipropionate (BDP) formulation into ex-vivo porcine skin. We found that the obelisk shaped MAPs are more durable compared to the conical and square pyramidal-shaped MAPs. When the obelisk shaped MAPs were used in combination with the oleogel-based BDP formulation, the amount of BDP penetrating the skin was significantly increased with greater needle lengths.
Hemin‐induced platelet activation is regulated by the ACKR3 chemokine surface receptor and has implications for passivation of vulnerable atherosclerotic plaques
2024-10-10

In vulnerable atherosclerotic plaques, intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release of hemoglobin and free hemin. Hemin activates platelets and leads to thrombosis. Agonism of the inhibitory platelet receptor ACKR3 inhibits hemin‐dependent platelet activation and thrombus formation. To characterize the effect of hemin and ACKR3 agonism on isolated human platelets, multi‐color flow cytometry and classical experimental setup such as light transmission aggregometry and a flow chamber assay were used. Hemin induces platelet aggregation and ex vivo platelet‐dependent thrombus formation on immobilized collagen under a low shear rate of 500 s −1 , indicating that free hemin is a strong activator of platelet‐dependent thrombosis. Recently, we described that ACKR3 is a prominent inhibitory receptor of platelet activation. Specific ACKR3 agonists but not conventional antiplatelet compounds such as COX‐1 inhibitor (indometacin), ADP‐receptor blocker (cangrelor), or PAR1 inhibitor (ML161) inhibit both hemin‐dependent aggregation and thrombus formation. To further characterize the effect of hemin on platelet subpopulations, we established a multi‐color flow cytometry assay. We found that hemin induces procoagulant (CD42b pos /PAC‐1 neg /AnnexinV pos ), aggregatory (CD42b pos /PAC‐1 pos /AnnexinV neg ), and inflammatory (CD42b pos /CXCR4 pos /ACKR3 pos /AnnexinV pos ) platelet subpopulations. Treatment with ACKR3 agonists significantly decreased the formation of procoagulant and ACKR3 pos platelets in response to hemin. We conclude that hemin is a strong activator for the formation of procoagulant platelets and thrombus formation which is dependent on the function of ACKR3. Activation of ACKR3 using specific agonists may offer a therapeutic strategy to regulate the vulnerability of atherosclerotic plaques in areas of IPH.
Not taught in medical school but needed for the clinical job – leadership, communication and career management skills for final year medical students
2024-10-10

Abstract Background Starting the first job as a young physician is a demanding challenge. Certain skills are important to master this transformation that go beyond the theoretical knowledge and practical skills taught in medical school. Competencies such as communication, leadership and career management skills are important to develop as a young physician but are usually not sufficiently taught in medical school in a structured and comprehensive way. Methods We performed an online survey among final year medical students regarding how they perceive their current competency level in communication, leadership and career management skills. We also assessed how they rate the importance to acquire these competencies and the current emphasis during their medical school education regarding these topics. Results Of 450 final year medical students 80 took part in the voluntary survey and 75 complete datasets were returned (16.7%). The majority of respondents rated different communication skills, leadership skills and career management skills as important or very important for their later clinical work. However, most students felt to be poorly or very poorly prepared by the current medical school curriculum, especially for certain leadership and career management skills. Overall, 90.7% of participants expressed interest in an additional educational course that covers subjects of communication, leadership and career management skills during the later stage of medical school, preferably as a hybrid in-person session that also offers synchronous online participation. Conclusions The results of the survey express the need to address communication, leadership and career management skills in the medical curriculum to be better prepare students for the demands of residency and their further course as physicians. An educational format during the final year of medical school may be suitable to address mentioned topics in the framework of clinical practical exposure.
Discourse comprehension and referential processing: effects of contextual distance and semantic plausibility on presupposition processing
2024-10-10

Abstract The present study aimed to investigate whether contextual factors influence how a reference is processed in discourse. We used intact and violated presuppositions (PSP), triggered by a definite or indefinite noun phrase, to monitor the reference process. In one sentence set, a contextual referent was explicitly mentioned close or far from the PSP-triggering noun phrase ( memory context ). In another sentence set, a referent was not explicitly mentioned in the context, but an inference to a referent was either plausible or implausible due to contextual semantic relations ( inference context ). Participants were asked to rate the coherence of the discourse after listening to it. Our results revealed a strong influence of the temporal distance of the contextual presentation of a referent. When the referent was far in the context ( memory context ), PSP violations were judged to be less severe than for close referents, suggesting that they are less clearly represented in memory. Furthermore, PSP violations seemed to play a subordinate role when the semantic context provided a basis for the plausible presence of a referent ( inference context ). Our results suggest that discourse comprehension involves referential processes whose importance may fade with distance in memory or may be obscured by semantic contextual content.
Naturalistic assessments across the lifespan: Systematic review of inhibition measures in ecological settings
2024-10-10

Inhibitory control is essential for our everyday lives. Despite this, it is commonly assessed using non-naturalistic assessments. In this systematic review, we argue for the importance of taking an ecological approach to assess cognition. The aims are to present the state-of-knowledge in naturalistic assessments of inhibitory control, focusing on their methodological characteristics, including psychometric properties and user experience. PubMed, PsycINFO and Web of Science were searched until September 2024. Studies were included if they used at least one naturalistic method of assessing inhibition. The included studies (N=64) were grouped into three methodological categories: gamification, virtual reality, and brief, repeated assessments in participants' usual environment in the form of ecological momentary assessments. Sample sizes spanned three orders of magnitude (N=12-22,098). We report considerable heterogeneity in the types of tasks used, and the psychometric details reported. Nonetheless, naturalistic tasks were generally comparable with standardised equivalents, although some tasks assessed mixed-domain constructs. Tasks were feasible and acceptable for participants, with generally high completion rates and engagement. Recommendations for future research are discussed.
Drivers of woody dominance across global drylands
2024-10-11

Increases in the abundance of woody species have been reported to affect the provisioning of ecosystem services in drylands worldwide. However, it is virtually unknown how multiple biotic and abiotic drivers, such as climate, grazing, and fire, interact to determine woody dominance across global drylands. We conducted a standardized field survey in 304 plots across 25 countries to assess how climatic features, soil properties, grazing, and fire affect woody dominance in dryland rangelands. Precipitation, temperature, and grazing were key determinants of tree and shrub dominance. The effects of grazing were determined not solely by grazing pressure but also by the dominant livestock species. Interactions between soil, climate, and grazing and differences in responses to these factors between trees and shrubs were key to understanding changes in woody dominance. Our findings suggest that projected changes in climate and grazing pressure may increase woody dominance in drylands, altering their structure and functioning.
Gallatabenzene Ligands Emerging from Open Lutetocene and Yttrocene Methyl Complexes
2024-10-11

Abstract Utilizing ternary mixtures [LnMe 3 ] n /K(2,4‐dtbp)/GaMe 3 (Ln=Lu, Y; 2,4‐dtbp=2,4‐di‐ tert ‐butyl‐pentadienyl), a series of metallacycles is accessible v ia tandem salt metathesis/deprotonation. Depending on the precursor molar ratio, both gallatabenzene and lutetacyclic moieties with fully planar metallacycles are obtained, which were further analyzed using DFT calculations. The precursor molar ratio affects the extent of pentadienyl C−H‐bond activation and oligomerization to tetra‐ and pentametallic arrays. Reacting a 1 : 2 : 2 mixture at −40 °C gave the open sandwich methyl complex (2,4‐dtbp) 2 Lu(CH 3 ), displaying a vital intermediate for subsequent ring‐closure reactions.
Full-length Cryptochrome 1 in the outer segments of the retinal blue cone photoreceptors in humans and great apes suggests a role beyond transcriptional repression
2024-10-11

Abstract Mammalian cryptochrome 1 (CRY1) is a central player in the circadian transcription-translation feedback loop, crucial for maintaining a roughly 24-hour rhythm. CRY1 was suggested to also function as blue-light photoreceptor in humans and has been found to be expressed at the mRNA level in various cell types of the inner retina. However, attempts to detect CRY1 at the protein level in the human retina have remained unsuccessful so far. Using various C-terminal specific antibodies recognizing full-length CRY1 protein, we consistently detected selective labelling in the outer segments of short wavelength-sensitive (SWS1, “blue”) cone photoreceptor cells across human, bonobo, and gorilla retinae. No other retinal cell types were stained, which is in contrast to what would be expected of a ubiquitous clock protein. Subcellular fractionation experiments in transfected HEK cells using a C-terminal specific antibody located full-length CRY1 in the cytosol and membrane fractions. Our findings indicate that human CRY1 has several different functions including at least one non-clock function. Our results also raise the likely possibility that several different versions of CRY1 exists in humans. We suggest that truncation of the C-terminal tail, maybe to different degrees, may affect the localization and function of human CRY1.
Data Descriptor for “Understanding and Perception of Automated Text Generation among the Public: Two Surveys with Representative Samples in Germany”
2024-10-11

With the release of ChatGPT, text-generating AI became accessible to the general public virtually overnight, and automated text generation (ATG) became the focus of public debate. Previously, however, little attention had been paid to this area of AI, resulting in a gap in the research on people’s attitudes and perceptions of this technology. Therefore, two representative surveys among the German population were conducted before (March 2022) and after (July 2023) the release of ChatGPT to investigate people’s attitudes, concepts, and knowledge on ATG in detail. This data descriptor depicts the structure of the two datasets, the measures collected, and potential analysis approaches beyond the existing research paper. Other researchers are encouraged to take up these data sets and explore them further as suggested or as they deem appropriate.
EthoCRED: a framework to guide reporting and evaluation of the relevance and reliability of behavioural ecotoxicity studies
2024-10-12

ABSTRACT Behavioural analysis has been attracting significant attention as a broad indicator of sub‐lethal toxicity and has secured a place as an important subdiscipline in ecotoxicology. Among the most notable characteristics of behavioural research, compared to other established approaches in sub‐lethal ecotoxicology (e.g. reproductive and developmental bioassays), are the wide range of study designs being used and the diversity of endpoints considered. At the same time, environmental hazard and risk assessment, which underpins regulatory decisions to protect the environment from potentially harmful chemicals, often recommends that ecotoxicological data be produced following accepted and validated test guidelines. These guidelines typically do not address behavioural changes, meaning that these, often sensitive, effects are not represented in hazard and risk assessments. Here, we propose a new tool, the EthoCRED evaluation method, for assessing the relevance and reliability of behavioural ecotoxicity data, which considers the unique requirements and challenges encountered in this field. This method and accompanying reporting recommendations are designed to serve as an extension of the “Criteria for Reporting and Evaluating Ecotoxicity Data (CRED)” project. As such, EthoCRED can both accommodate the wide array of experimental design approaches seen in behavioural ecotoxicology, and could be readily implemented into regulatory frameworks as deemed appropriate by policy makers of different jurisdictions to allow better integration of knowledge gained from behavioural testing into environmental protection. Furthermore, through our reporting recommendations, we aim to improve the reporting of behavioural studies in the peer‐reviewed literature, and thereby increase their usefulness to inform chemical regulation.
Targeting KDM1A in Neuroblastoma with NCL-1 Induces a Less Aggressive Phenotype and Suppresses Angiogenesis
2024-10-12

Background: The KDM1A histone demethylase regulates the cellular balance between proliferation and differentiation, and is often deregulated in human cancers including the childhood tumor neuroblastoma. We previously showed that KDM1A is strongly expressed in undifferentiated neuroblastomas and correlates with poor patient prognosis, suggesting a possible clinical benefit from targeting KDM1A. Methods: Here, we tested the efficacy of NCL-1, a small molecule specifically inhibiting KDM1A in preclinical models for neuroblastoma. Results: NCL-1 mimicked the effects of siRNA-mediated KDM1A knockdown and effectively inhibited KDM1A activity in four neuroblastoma cell lines and a patient-representative cell model. KDM1A inhibition shifted the aggressive tumor cell phenotypes towards less aggressive phenotypes. The proliferation and cell viability was reduced, accompanied by the induction of markers of neuronal differentiation. Interventional NCL-1 treatment of nude mice harboring established neuroblastoma xenograft tumors reduced tumor growth and inhibited cell proliferation. Reduced vessel density and defects in blood vessel construction also resulted, and NCL-1 inhibited the growth and tube formation of HUVEC-C cells in vitro. Conclusions: Inhibiting KDM1A could attack aggressive neuroblastomas two-fold, by re-directing tumor cells toward a less aggressive, slower-growing phenotype and by preventing or reducing the vascular support of large tumors.
A consistent estimator for confounding strength
2024-10-13

Regression on observational data can fail to capture a causal relationship in the presence of unobserved confounding. Confounding strength measures this mismatch, but estimating it requires itself additional assumptions. A common assumption is the independence of causal mechanisms, which relies on concentration phenomena in high dimensions. While high dimensions enable the estimation of confounding strength, they also necessitate adapted estimators. In this paper, we derive the asymptotic behavior of the confounding strength estimator by Janzing and Schölkopf (2018) and show that it is generally not consistent. We then use tools from random matrix theory to derive an adapted, consistent estimator.
Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?
2024-10-14

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1–based therapies are under development. For future development of GLP-1–based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.
Impact of Surface Enhanced Raman Spectroscopy in Catalysis
2024-10-14

Catalysis stands as an indispensable cornerstone of modern society, underpinning the production of over 80% of manufactured goods and driving over 90% of industrial chemical processes. As the demand for more efficient and sustainable processes grows, better catalysts are needed. Understanding the working principles of catalysts is key, and over the last 50 years, surface-enhanced Raman Spectroscopy (SERS) has become essential. Discovered in 1974, SERS has evolved into a mature and powerful analytical tool, transforming the way in which we detect molecules across disciplines. In catalysis, SERS has enabled insights into dynamic surface phenomena, facilitating the monitoring of the catalyst structure, adsorbate interactions, and reaction kinetics at very high spatial and temporal resolutions. This review explores the achievements as well as the future potential of SERS in the field of catalysis and energy conversion, thereby highlighting its role in advancing these critical areas of research.
Cluster-efficient pangenome graph construction with nf-core/pangenome
2024-10-14

Abstract Motivation Pangenome graphs offer a comprehensive way of capturing genomic variability across multiple genomes. However, current construction methods often introduce biases, excluding complex sequences or relying on references. The PanGenome Graph Builder (PGGB) addresses these issues. To date, though, there is no state-of-the-art pipeline allowing for easy deployment, efficient and dynamic use of available resources, and scalable usage at the same time. Results To overcome these limitations, we present nf-core/pangenome, a reference-unbiased approach implemented in Nextflow following nf-core’s best practices. Leveraging biocontainers ensures portability and seamless deployment in High-Performance Computing (HPC) environments. Unlike PGGB, nf-core/pangenome distributes alignments across cluster nodes, enabling scalability. Demonstrating its efficiency, we constructed pangenome graphs for 1000 human chromosome 19 haplotypes and 2146 Escherichia coli sequences, achieving a two to threefold speedup compared to PGGB without increasing greenhouse gas emissions. Availability and implementation nf-core/pangenome is released under the MIT open-source license, available on GitHub and Zenodo, with documentation accessible at https://nf-co.re/pangenome/docs/usage.