julilili42/papers huggingface dataset:
Heat Treatment of Chert in the Early Mesolithic at Rottenburg-Siebenlinden (Southwest Germany)
2023-08-18

Unambiguous evidence for heat treatment in the Early Mesolithic of Southwestern Germany is thus far restricted to one type of raw material and to cave sites of the Swabian Jura region. At the open-air site Rottenburg-Siebenlinden, heat treatment of an additional raw material was proposed. In this paper, we reexamine the lithic assemblage of horizon III, using the best available criterion for recognizing heat treatment: gloss contrast. Through technological analysis of these diagnostic artefacts, we investigate the timing of heat treatment within the reduction sequence. Visual identifications were substantiated by analyzing surface roughness of gloss contrast artefacts. Our results show that heat treatment was regularly applied to a wider range of raw materials than previously thought, during blank production. These findings highlight that the last Central European hunter-gatherers were flexible in terms of material choices and that heat treatment was a more widespread phenomenon than previously thought.
Plaque vicinity as a hotspot of microglial turnover in a mouse model of Alzheimer's disease
2023-08-19

Abstract Microglia, the major immune cells of the brain, are functionally heterogeneous but in vivo functional properties of these cells are rarely studied at single‐cell resolution. By using microRNA‐9 regulated viral vectors for multicolor labeling and longitudinal in vivo monitoring of individual microglia, we followed their fate in the cortex of healthy adult mice and at the onset of amyloidosis in a mouse model of Alzheimer's disease. In wild‐type mice, microglia were rather mobile (16% of the cells migrated at least once in 10–20 days) but had a low turnover as documented by low division and death rates. Half of the migratory events were tightly associated with blood vessels. Surprisingly, basic migration properties of microglia (i.e., fraction of migrating cells, saltatory migration pattern, speed of migration, translocation distance, and strong association with blood vessels) were preserved in amyloid‐depositing brains, despite amyloid plaques becoming the major destination of migration. Besides, amyloid deposition significantly increased microglial division and death rates. Moreover, the plaque vicinity became a hotspot of microglial turnover, harboring 33% of all migration, 70% of death and 54% of division events.
Higher education students differ in their technology use
2023-08-19

Digital media are widely used among Higher Education (HE) students; however, it is not clear yet how students from different disciplines apply learning technology. When differences in technology use were found among disciplines, they were identified broadly, for example, between soft and hard sciences, that is, social sciences/humanities vs. natural sciences. Beyond this, disciplines may also differ according to their traditions, norms and values that form their discipline-specific cultures. Thus, based on the theoretical perspectives of social cognitive theory and organisational culture, this present study aimed to examine students’ technology use in different HE disciplines. In a multilevel analysis, data from four German universities were analyzed, including more than 1,200 students from 105 disciplines. The findings suggest that students in different disciplines vary substantially in their average use of study-related technology. Furthermore, on the individual level, study-related technology use depends on individual factors, e.g., perceived usefulness. This present study's results contribute to further extending our knowledge about student technology use in HE. Above all, the conceptual and methodical models can serve as a theoretical and empirical basis for future studies. To analyze disciplinary differences, the study shows that a rough classification, for example hard versus soft disciplines, is not sufficient. Instead, the different disciplines need to be distinguished.
Comparative analysis of YAP/TEAD inhibitors in 2D and 3D cultures of primary human hepatocytes reveals a novel non-canonical mechanism of CYP induction
2023-08-20

Induction of cytochrome P450 (CYP) genes constitutes an important cause of drug-drug interactions and preclinical evaluation of induction liability is mandatory for novel drug candidates. YAP/TEAD signaling has emerged as an attractive target for various oncological indications and multiple chemically distinct YAP/TEAD inhibitors are rapidly progressing towards clinical stages. Here, we tested the liability for CYP induction of a diverse set of YAP/TEAD inhibitors with different modes of action and TEAD isoform selectivity profiles in monolayers and 3D spheroids of primary human hepatocytes (PHH). We found that YAP/TEAD inhibition resulted in broad induction of CYPs in 2D monolayers, whereas, if at all, only marginal induction was seen in spheroid culture. Comprehensive RNA-Seq indicated that YAP/TEAD signaling was increased in 2D culture compared to spheroids, which was paralleled by elevated activities of the interacting transcription factors LXR and ESRRA, likely at least in part due to altered mechanosensing. Inhibition of this YAP/TEAD hyperactivation resulted in an overall reduction of hepatocyte dedifferentiation marked by increased hepatic functionality, including CYPs. These results thus demonstrate that the observed induction is due to on-target effects of the compounds rather than direct activation of xenobiotic sensing nuclear receptors. Combined, the presented data link hepatocyte dedifferentiation to YAP/TEAD dysregulation, reveal a novel non-canonical pathway of CYP induction and highlight the advantage of organotypic 3D cultures to predict clinically relevant pharmacokinetic properties, particularly for atypical induction mechanisms.
Effects of Scaffolds on Urine- and Urothelial Carcinoma Tissue-Derived Organoids from Bladder Cancer Patients
2023-08-20

Organoids are three-dimensional constructs generated by placing cells in scaffolds to facilitate the growth of cultures with cell–cell and cell–matrix interactions close to the in vivo situation. Organoids may contain different types of cells, including cancer cells, progenitor cells, or differentiated cells. As distinct culture conditions have significant effects on cell metabolism, we explored the expansion of cells and expression of marker genes in bladder cancer cells expanded in two different common scaffolds. The cells were seeded in basement membrane extract (BME; s.c., Matrigel®) or in a cellulose-derived hydrogel (GrowDex®, GD) and cultured. The size of organoids and expression of marker genes were studied. We discovered that BME facilitated the growth of significantly larger organoids of cancer cell line RT112 (p &lt; 0.05), cells from a solid tumor (p &lt; 0.001), and a voiding urine sample (p &lt; 0.001). Expression of proliferation marker Ki76, transcription factor TP63, cytokeratin CK20, and cell surface marker CD24 clearly differed in these different tumor cells upon expansion in BME when compared to cells in GD. We conclude that the choice of scaffold utilized for the generation of organoids has an impact not only on cell growth and organoid size but also on protein expression. The disadvantages of batch-to-batch-variations of BME must be balanced with the phenotypic bias observed with GD scaffolds when standardizing organoid cultures for clinical diagnoses.
Nonequilibrium thermodynamics and power generation in open quantum optomechanical systems
2023-08-21

Cavity optomechanical systems are a paradigmatic setting for the conversion of electromagnetic energy into mechanical work. Experiments with atoms coupled to cavity modes are realized in nonequilibrium conditions, described by phenomenological models encoding nonthermal dissipative dynamics and falling outside the framework of weak system-bath couplings. This fact makes their interpretation as quantum engines, e.g., the derivation of a well-defined efficiency, quite challenging. Here, we present a consistent thermodynamic description of open quantum cavity-atom systems. Our approach takes advantage of their nonequilibrium nature and arrives at an energetic balance which is fully interpretable in terms of persistent dissipated heat currents. The interaction between atoms and cavity modes can further give rise to nonequilibrium phase transitions and emergent behavior and allows us to assess the impact of collective many-body phenomena on the engine operation. To enable this, we define two thermodynamic limits, one related to a weak optomechanical coupling and one related to a strong optomechanical coupling. We illustrate our ideas by focusing on a time-crystal engine and discuss power generation, energy-conversion efficiency, and the emergence of metastable behavior in these limits.
Assessing ChatGPT’s Mastery of Bloom’s Taxonomy using psychosomatic medicine exam questions
2023-08-21

Abstract Introduction Large language models (LLMs) such as GPT-4 are increasingly used in medicine and medical education. However, these models are prone to “hallucinations” – outputs that sound convincing while being factually incorrect. It is currently unknown how these errors by LLMs relate to the different cognitive levels defined in Bloom’s Taxonomy. Methods We used a large dataset of psychosomatic medicine multiple-choice questions (MCQ) (N = 307) with real-world results derived from medical school exams. GPT-4 answered the MCQs using two distinct prompt versions – detailed and short. The answers were analysed using a quantitative and qualitative approach. We focussed on incorrectly answered questions, categorizing reasoning errors according to Bloom’s Taxonomy. Results GPT-4’s performance in answering exam questions yielded a high success rate: 93% (284/307) for the detailed prompt and 91% (278/307) for the short prompt. Questions answered correctly by GPT-4 had a statistically significant higher difficulty compared to questions that GPT-4 answered incorrectly (p=0.002 for the detailed prompt and p&lt;0.001 for the short prompt). Independent of the prompt, GPT-4’s lowest exam performance was 78.9%, always surpassing the pass threshold. Our qualitative analysis of incorrect answers, based on Bloom’s Taxonomy, showed errors mainly in the “remember” (29/68) and “understand” (23/68) cognitive levels. Specific issues arose in recalling details, understanding conceptual relationships, and adhering to standardized guidelines. Discussion GPT-4 displayed a remarkable success rate when confronted with psychosomatic medicine multiple-choice exam questions, aligning with previous findings. When evaluated against Bloom’s hierarchical framework, our data revealed that GPT-4 occasionally ignored specific facts (“remember”), provided illogical reasoning (“understand”), or failed to apply concepts to a new situation (“apply”). These errors, though confidently presented, could be attributed to inherent model biases and the tendency to generate outputs that maximize likelihood. Conclusion While GPT-4 mostly excels at medical exam questions, discerning its occasional cognitive errors is crucial.
Public health impact of antihypertensive medication use on arterial blood pressure: A pooled cross-sectional analysis of population health surveys
2023-08-21

The early initiation of antihypertensive drug therapy is conceived as one of the most important public health interventions addressing cardiovascular risk in the population. However, the actual contribution of this public health intervention to reduce blood pressure (BP) at the population level is largely unknown. Hence, the aim of the present investigation is to estimate the potential public health effects of the use of antihypertensive medication on BP in the population aged 16 and older. Data from three population health surveys periodically conducted in the United States, England, and Scotland are analysed ( N = 362,275). The secular trends of BP measurements and the potential public health impact of the use of antihypertensive medications on BP over time are analysed in a series of linear mixed models. Between 1992 and 2019, a secular trend of decreasing systolic and diastolic BP occurred (−16.24 99% CI [−16.80; −15.68] and −3.08 99% CI [−3.36; −2.80] mmHg, respectively). The potential public health impact of the use of antihypertensive medications in the period 1992–2019 on systolic BP was estimated to lie between −8.56 99% CI [−8.34; −8.77] and −8.68 99% CI [−8.33; −9.03] mmHg. Average reduction of diastolic BP was in the range of −5.56 99% CI [−5.71; −5.42] and −6.55 99% CI [−6.78; −6.32] mmHg. The observed changes in the distribution of BP measurements over time were found to be more strongly related to secular trends affecting the whole populations, rather than to increases in the proportion of individuals taking antihypertensive medications.
Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity
2023-08-21

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders.
The evidential future in Italian
2023-08-21

Abstract This paper provides a systematic description and analysis of the non-predictive use of the Italian future. Several authors claim that, on this use, the Italian future is an evidential (Squartini 2001, Mari 2010, Eckardt and Beltrama 2019, Frana and Menéndez-Benito 2019). Others argue that the non-predictive future does not directly contribute an evidential signal (e.g., Giannakidou and Mari 2018, Farkas and Ippolito 2022). We side with the evidential camp. From an empirical standpoint, we present the results of a battery of tests that show that the non-predictive future patterns with evidentials cross-linguistically. From a theoretical standpoint, we put forward an analysis that combines a slightly modified version of the proposal for evidentials in Davis et al. (2007) with Schlenker’s (2007) view of expressive content. On this account, the Italian evidential future (i) lowers the quality threshold required to perform a successful speech act (Davis et al. 2007) and (ii) triggers an evidential presupposition relativized to the speaker’s beliefs (modeled after Schlenker’s analysis of expressives). Our treatment of the evidential component as an expressive presupposition opens up a new perspective on the study of evidentiality and highlights the need for further detailed empirical studies exploring the extent to which this perspective is applicable cross-linguistically.
Unraveling haplotype errors in the DFNA33 locus
2023-08-21

Genetic heterogeneity makes it difficult to identify the causal genes for hearing loss. Studies from previous decades have mapped numerous genetic loci, providing critical supporting evidence for gene discovery studies. Despite widespread sequencing accessibility, many historically mapped loci remain without a causal gene. The DFNA33 locus was mapped in 2009 and coincidentally contains ATP11A , a gene recently associated with autosomal dominant hearing loss and auditory neuropathy type 2. In a rare opportunity, we genome-sequenced a member of the original family to determine whether the DFNA33 locus may also be assigned to ATP11A . We identified a deep intronic variant in ATP11A that showed evidence of functionally normal splicing. Furthermore, we re-assessed haplotypes from the originally published DFNA33 family and identified two double recombination events and one triple recombination event in the pedigree, a highly unlikely occurrence, especially at this scale. This brief research report also serves as a call to the community to revisit families who have previously been involved in gene mapping studies, provide closure, and resolve these historical loci.
EuCARE-POSTCOVID Study: A Multicentre Cohort Study on Long-Term Post-COVID-19 Manifestations
2023-08-21

Abstract Background. Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10-20% of patients and reaching 50-60% in certain cohorts, while the associated risk factors remain poorly understood. Methods. This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period. Patients will be followed up at the post-COVID-19 clinic of each centre at 2-3, 6-9, and 12-15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders. Discussion . This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs. Trial registration: This study has been registered with ClinicalTrials.gov under the identifier NCT05531773.
The Picard index of a surface with torus action
2023-08-21

We consider normal rational projective surfaces with torus action and provide a formula for their Picard index, that means the index of the Picard group inside the divisor class group. As an application, we classify the log del Pezzo surfaces with torus action of Picard number one up to Picard index 10,000.
The Minimum Variation Timescales of X-Ray Bursts from SGR J1935+2154
2023-08-22

Abstract The minimum variation timescale (MVT) of soft gamma-ray repeaters can be an important probe to estimate the emission region in pulsar-like models, as well as the Lorentz factor and radius of the possible relativistic jet in gamma-ray burst (GRB)–like models, thus revealing their progenitors and physical mechanisms. In this work, we systematically study the MVTs of hundreds of X-ray bursts (XRBs) from SGR J1935+2154 observed by Insight-HXMT, GECAM, and Fermi/Gamma-ray Burst Monitor from 2014 July to 2022 January through the Bayesian block algorithm. We find that the MVTs peak at ∼2 ms, corresponding to a light-travel time size of about 600 km, which supports the magnetospheric origin in pulsar-like models. The shock radius and the Lorentz factor of the jet are also constrained in GRB-like models. Interestingly, the MVT of the XRB associated with FRB 200428 is ∼70 ms, which is longer than that of most bursts and implies its special radiation mechanism. In addition, the median of MVTs is 7 ms, shorter than the median MVTs of 40 ms and 480 ms for short GRBs or long GRBs, respectively. However, the MVT is independent of duration, similar to GRBs. Finally, we investigate the energy dependence of MVT and suggest that there is a marginal evidence for a power-law relationship like GRBs, but the rate of variation is at least about an order of magnitude smaller. These features may provide an approach to identify bursts with a magnetar origin.
Geodatenkultur der Diversität: eine neopragmatische Skizzierung
2023-08-22

Abstract In recent years, fundamental changes regarding geospatial data resources have become apparent. The establishment of gaming software and associated web-based exchange and communication platforms offer cartography and geoinformation sciences new potentials of geospatial data, which requires a rethinking, especially in the field of 3D visualization. The resources of official geospatial data holding agencies and first VGI communities from early times of digitization are extended by geospatial data originating from 3D modeling in gaming and containing high creative potential. Here, in relation to the availability of geodata resources, a change in the geospatial data culture becomes apparent, from a geospatial data culture of dependency (ca. 1830–1980), to a geospatial data culture of participation (ca. 1980–2020), to its further development to a geospatial data culture of diversity (since ca. 2020). These three paradigms of a geospatial data culture are discussed in this paper, after a conceptual reflection that builds on a neopragmatic understanding. Case studies are based on virtual and augmented reality. With these examples, the synthesis of different geospatial data resources for targeted 3D cartographic applications is highlighted.
Defining Oligometastatic Bladder Cancer: A Systematic Review
2023-08-22

Oligometastatic bladder cancer is a disease state in which favorable outcomes can be expected after a treatment combination of systemic therapy, plus surgery and/or radiotherapy for sites of bladder cancer metastasis. Our systematic review showed a lack of meaningful evidence to define this disease state. There is an urgent need to develop organized research in this field.