julilili42/papers huggingface dataset:
Medical Students’ Attitudes toward AI in Medicine and their Expectations for Medical Education
2023-07-23

Abstract Objectives Artificial intelligence (AI) is used in a variety of contexts in medicine. This involves the use of algorithms and software that analyze digital information to make diagnoses and suggest adapted therapies. It is unclear, however, what medical students know about AI in medicine, how they evaluate its application, and what they expect from their medical training accordingly. In the study presented here, we aimed at providing answers to these questions. Methods In this survey study, we asked medical students about their assessment of AI in medicine and recorded their ideas and suggestions for considering this topic in medical education. Fifty-eight medical students completed the survey. Results Almost all participants were aware of the use of AI in medicine and had an adequate understanding of it. They perceived AI in medicine to be reliable, trustworthy, and technically competent, but did not have much faith in it. They considered AI in medicine to be rather intelligent but not anthropomorphic. Participants were interested in the opportunities of AI in the medical context and wanted to learn more about it. They indicated that basic AI knowledge should be taught in medical studies, in particular, knowledge about modes of operation, ethics, areas of application, reliability, and possible risks. Conclusions We discuss the implications of these findings for the curricular development in medical education. Medical students need to be equipped with the knowledge and skills to use AI effectively and ethically in their future practice. This includes understanding the limitations and potential biases of AI algorithms by teaching the sensible use of human oversight and continuous monitoring to catch errors in AI algorithms and ensure that final decisions are made by human clinicians.
Principles and Applications of CF2X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery
2023-07-24

As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF<sub>2</sub>X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF<sub>2</sub>X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF<sub>2</sub>X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, reveals a highly interesting binding mode for fragment <b>23</b> in JNK3, featuring an XB of CF<sub>2</sub>Br toward the P-loop, as well as chalcogen bonds. We suggest that underexplored chemical space combined with unconventional binding modes provides excellent opportunities for patentable chemotypes for therapeutic intervention.
JUNO sensitivity on proton decay p → ν K + searches*
2023-07-24

Abstract The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via is 36.9% ± 4.9% with a background level of events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies.
The revised International Code of Medical Ethics: an exercise in international professional ethical self-regulation
2023-07-24

The World Medical Association (WMA), the global representation of the medical profession, first adopted the International Code of Medical Ethics (ICoME) in 1949 to outline the professional duties of physicians to patients, other physicians and health professionals, themselves and society as a whole. The ICoME recently underwent a major 4-year revision process, culminating in its unanimous adoption by the WMA General Assembly in October 2022 in Berlin. This article describes and discusses the ICoME, its revision process, the controversial and uncontroversial issues, and the broad consensus achieved among WMA constituent members, representing over 10 million physicians worldwide. The authors analyse the ICoME, including its response to contemporary changes and challenges like ethical plurality and globalisation, in light of ethical theories and approaches, reaching the conclusion that the document is a good example of international ethical professional self-regulation.
Chiral and trace anomalies in deeply virtual Compton scattering. II. QCD factorization and beyond
2023-07-24

We extend the discussion of the recently discovered “anomaly poles” in QCD Compton scattering. We perform the complete one-loop calculation of the Compton amplitude using momentum transfer t as the regulator of collinear divergences. In the gluon channel, we confirm the presence of poles 1/t in both the real and the imaginary parts of the amplitude. In the quark channel, we find unexpected infrared single 1/ε and double 1/ε&lt;sup&gt;2&lt;/sup&gt; poles. We then perform the one-loop calculation of the leading-twist quark generalized parton distributions (GPDs) for quark and gluon external states with the same regulators and find that all these singular terms can be systematically absorbed into the GPDs, showing that QCD factorization is restored to this order. Having established this, we discuss the fate of the 1/t poles. We argue that they become the nonperturbative building blocks of GPDs that encode the chiral and trace anomalies of QCD, in a way consistent with the known constraints these anomalies impose on the nucleon axial and gravitational form factors. The scope of research on GPDs can therefore be expanded to address the manifestation and implications of quantum anomalies in high-energy exclusive processes.
Perspectivalism about temporal reality
2023-07-24

Abstract It is usually agreed that reality is temporal in the sense of containing entities that exist in time, but some philosophers, roughly those who have been traditionally called A-theorists, hold that reality is temporal in a far more profound sense than what is implied by the mere existence of such entities. This hypothesis of deep temporality typically involves two ideas: that reality is temporally compartmentalised into distinct present, past, and future ‘realms’, and that this compartmentalisation is temporally dynamic in the sense that the boundaries of those temporal realms change from one moment to the next. The truth of something like this hypothesis is commonly thought to require that at least some of the facts that fundamentally constitute reality be tensed . While this seems plausible, realism about fundamental tensed facts does not seem to entail deep temporality. Nor is it clear exactly what realism about tense amounts to, given that no informative answer has been given to the question of what it is for a fact to be tensed. In this paper, I introduce a novel approach, perspectivalism about temporal reality , that seeks to vindicate the hypothesis of deep temporality by ascribing to reality a certain kind of temporally perspectival structure, which also provides a straightforward answer to the question of what the tensedness of facts consists in as well as to the question of what it is for reality to be constituted by such facts.
Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS
2023-07-24

Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons. Several functionally heterogeneous genes have been associated with the familial form of this disorder (fALS), depicting an extremely complex pathogenic landscape. This heterogeneity has limited the identification of an effective therapy, and this bleak prognosis will only improve with a greater understanding of convergent disease mechanisms. Recent evidence from human post-mortem material and diverse model systems has highlighted the synapse as a crucial structure actively involved in disease progression, suggesting that synaptic aberrations might represent a shared pathological feature across the ALS spectrum. To test this hypothesis, we performed the first comprehensive analysis of the synaptic proteome from post-mortem spinal cord and human iPSC-derived motoneurons carrying mutations in the major ALS genes. This integrated approach highlighted perturbations in the molecular machinery controlling vesicle release as a shared pathomechanism in ALS. Mechanistically, phosphoproteomic analysis linked the presynaptic vesicular phenotype to an accumulation of cytotoxic protein aggregates and to the pro-apoptotic activation of the transcription factor c-Jun, providing detailed insights into the shared pathobiochemistry in ALS. Notably, sub-chronic treatment of our iPSC-derived motoneurons with the fatty acid docosahexaenoic acid exerted a neuroprotective effect by efficiently rescuing the alterations revealed by our multidisciplinary approach. Together, this study provides strong evidence for the central and convergent role played by the synaptic microenvironment within the ALS spinal cord and highlights a potential therapeutic target that counteracts degeneration in a heterogeneous cohort of human motoneuron cultures.
Tissue‐based absolute quantification using large‐scale TMT and LFQ experiments
2023-07-24

Abstract Relative and absolute intensity‐based protein quantification across cell lines, tissue atlases and tumour datasets is increasingly available in public datasets. These atlases enable researchers to explore fundamental biological questions, such as protein existence, expression location, quantity and correlation with RNA expression. Most studies provide MS1 feature‐based label‐free quantitative (LFQ) datasets; however, growing numbers of isobaric tandem mass tags (TMT) datasets remain unexplored. Here, we compare traditional intensity‐based absolute quantification (iBAQ) proteome abundance ranking to an analogous method using reporter ion proteome abundance ranking with data from an experiment where LFQ and TMT were measured on the same samples. This new TMT method substitutes reporter ion intensities for MS1 feature intensities in the iBAQ framework. Additionally, we compared LFQ‐iBAQ values to TMT‐iBAQ values from two independent large‐scale tissue atlas datasets (one LFQ and one TMT) using robust bottom‐up proteomic identification, normalisation and quantitation workflows.
Differentially rotating scalarized neutron stars with realistic postmerger profiles
2023-07-24

The merger remnant of a binary neutron star coalescence is initially strongly differentially rotating. Some properties of these remnants can be accurately modeled through building equilibrium neutron star models. In the present paper, we study how a modification of general relativity, namely scalar-tensor theory with a massive scalar field, will alter the picture. In contrast to previous studies, we implement a realistic phenomenological differential rotational law which allows for neutron star models to attain maximal angular velocity away from the center. We find that solutions with much higher masses and angular momenta exist in scalar-tensor theory compared with general relativity. They keep their quasispherical energy-density distribution for significantly higher values of the angular momentum before transitioning to quasitoroidal models, in contrast to pure general relativity. Constructing such neutron star solutions is the first step to our final goal that is studying how scalarization alters the stability and gravitational wave emission of postmerger remnants.
Using Stop Motion Animations to Activate and Analyze High School Students’ Intuitive Resources about Reaction Mechanisms
2023-07-24

Mechanisms are part of the high school curriculum in many countries. Although research shows that university students struggle with mechanistic reasoning, very little is known about learning mechanisms in high school. Understanding the cognitive resources that high school students intuitively activate is critical to fostering meaningful learning. A readily available tool for modeling dynamic processes are stop-motion animations (SMAs). In this study, 55 high school students were asked to create SMAs of their intuitive ideas of nucleophilic substitution reactions. In a second step, the students evaluated two pre-made SMAs modeling the textbook-based stepwise (SN1) and concerted (SN2) mechanisms. Within the student-generated SMAs, SN1- and SN2-like mechanisms were equally distributed; after viewing the textbook-style animations, most students rated an SN2 mechanism as more likely. However, no group modeled both types of mechanisms or reasoned that both mechanisms were possible. Students used diverse chemical concepts as well as plausibility in their reasoning. However, simultaneous movement of atoms, conformational changes, and the idea of competing and boundary mechanisms do not seem intuitive. In conclusion, SMAs were found to be an appropriate tool for activating, analyzing, and discussing students’ resources “on the fly”, and these ideas can serve as a starting point for promoting productive mechanistic reasoning.
Back in Person: Frontiers in Medicinal Chemistry 2023
2023-07-24

Abstract The Frontiers in Medicinal Chemistry (FiMC) is the largest international Medicinal Chemistry conference in the German speaking area and took place from April 3 rd to 5 th 2023 in Vienna (Austria). Fortunately, after being cancelled in 2020 and two years (2021–2022) of entirely virtual meetings, due to the COVID‐19 pandemic, the FiMC could be held in a face‐to‐face format again. Organized by the Division of Medicinal Chemistry of the German Chemical Society (GDCh), the Division of Pharmaceutical and Medicinal Chemistry of the German Pharmaceutical Society (DPhG), together with the Division of Medicinal Chemistry of the Austrian Chemical Society (GÖCH), the Austrian Pharmaceutical Society (ÖPhG), and a local organization committee from the University of Vienna headed by Thierry Langer, the meeting brought together 260 participants from 21 countries. The program included 38 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 102 posters were presented in two highly interactive poster sessions.
A Parkinson’s disease genetic risk score associates with blood DNAm on chromosome 17
2023-07-24

Abstract Although Parkinson’s disease (PD) coincides with altered immune functioning, there are few reproducible associations between blood DNA methylation (DNAm) and PD case-control status. Integrative analyses of genotype and blood DNAm can address this gap and can help us characterize the biological function of PD genetic risk loci. First, we tested for associations between a PD genetic risk score (GRS) and DNAm. Our GRS included 36 independent genome-wide significant variants from the largest GWAS of PD to date. Our discovery sample was TERRE, consisting of French agricultural workers (71 PD cases and 147 controls). The GRS associated with DNAm at 85 CpG sites, with 19 associations replicated in an independent sample (DIG-PD). The majority of CpG sites (73) are within a 1.5 Mb window on chromosome 17, and 36 CpG sites annotate to MAPT and KANSL1 , neighboring genes that affect neurodegeneration. All associations were invariant to non-genetic factors, including exposure to commercial-grade pesticides, and omitting chromosome 17 variants from the GRS had little effect on association. Second, we compared our findings to the relationship between individual PD risk loci and blood DNAm using blood mQTL from a large independent meta-analysis (GoDMC). We found 79 CpG sites that colocalized with PD loci, and via summary Mendelian randomization analysis, we show 25/79 CpG sites where DNAm causally affects PD risk. The nine largest causal effects are within chromosome 17, including an effect within MAPT . Thus, all integrative analyses prioritized DNAm on chromosome 17, drawing from multiple independent data sets, meriting further study of this region.
Bridging Processes of Multiculturals and Multilinguals
2023-07-24

This study investigates how multicultural and multilingual employees develop and enact their particular capabilities to bridge cultural and language barriers in international work contexts. Although previous literature has already identified the usefulness of these individuals in overcoming such hurdles, we offer novel insights into how these employees not only use their assets but interestingly also their shortcomings to bridge cultural and language barriers. Based on an in-depth analysis of 154 interviews, we inductively develop a theoretical model of bridging activities that carefully distinguishes between the related, but still distinct, concepts of culture- and language-related bridging. We show the entire bridging processes based on assets on one hand, and shortcomings on the other including (1) antecedents to (2) capabilities and motivation, and (3) enactment. Based on this analysis, we develop four roles in bridging activities including: cultural teacher, language translator, cultural coach and language facilitator.
Digging Deep: The Roots of Gender Biases in Decision Making - The Case of Patent Examination
2023-07-24

We analyze gender biases and their underlying mechanisms in decision making in the context of the US patent examination process. Using United States Patent and Trademark Office [USPTO] data on 1,501,985 single inventor patent applications and their respective examiners between 1991 and 2021, we are able to identify biases against female inventors (compared to male inventors) and trace these biases back to two decision heuristics: representativeness and availability. It is important to differentiate representativeness and availability heuristics because they affect the outcome of decision making in different directions. Taking the dynamically changing individual decision context of the examiners into account, we find that representativeness heuristics are impacted by examiners' prior exposure to female inventor patent applications: gender biases decrease with increasing exposure. Additionally, we look at the effects of examiners' workload on the reliance of decision-making heuristics. We conclude by suggesting that the duality of
Complex variations in X-ray polarization in the X-ray pulsar LS V +44 17/RX J0440.9+4431
2023-07-25

We report on Imaging X-ray polarimetry explorer (IXPE) observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 made at two luminosity levels during the giant outburst in January–February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in supercritical and subcritical states with significantly different emission-region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase-resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on the pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations in the spin axis inclination, the position angle, and the magnetic colatitude by tens of degrees within the space of just a few days. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of an unpulsed polarized component in addition to the polarized radiation associated with the pulsar itself. We then show that the observed PA phase dependence in both observations can be explained with a single set of RVM parameters defining the pulsar’s geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation in the equatorial disk wind.
STE20‐type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies
2023-07-25

Abstract Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20‐type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC. By analyzing public datasets and in‐house cohorts, we found that hepatic MST3 and MST4 expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial‐mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4‐deficient hepatocytes and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4. These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.
Emotional Cues and the Demand for Televised Sports: Evidence from the UEFA Champions League
2023-07-25

This study provides first evidence on how belief dynamics are driving entertainment utility and consequently the demand for sports across markets by analyzing minute-by-minute audience data of UEFA Champions League (UCL) games televised in the UK and the Spanish market during a full (pre-COVID) cycle of broadcasting rights. Overall, we find that suspense and surprise are the main drivers of demand in both markets while shock only has marginal effects in the Spanish market. Interestingly, we find a combined impact of suspense and surprise in the UK market that is of similar magnitude as reported in a previous study for English Premier League matches in the UK. In the Spanish market, however, the combined impact is considerably larger.