julilili42/papers huggingface dataset:
Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age
2024-03-20

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.
[11C]MODAG 005 – a novel PET tracer targeting alpha-synuclein aggregates in the brain
2024-03-20

<title>Abstract</title> Synucleinopathies are neurodegenerative diseases characterized by the presence of brain inclusions containing the pathologically aggregated protein α-synuclein (αSYN). The development of a positron emission tomography tracer to detect aggregates of misfolded αSYN would revolutionize disease monitoring and the evaluation of therapeutic efficacy. Here we present the development and preclinical in vitro and in vivo validation of [ <sup>11</sup> C]MODAG-005. In vitro binding experiments demonstrate subnanomolar binding affinity to recombinant αSYN fibrils as well as to αSYN inclusions in human brain tissue. Specific binding in multiple system atrophy brain tissue was detected using autoradiography and microautoradiography, and was validated through immunostaining. In vivo, [ <sup>11</sup> C]MODAG-005 shows good brain penetration, rapid clearance from brain tissue and low metabolite formation in rodents and non-human primates. In addition, a pronounced binding and a good signal-to-noise ratio were achieved in an αSYN fibril-injected rat model and in an αSYN(A30P) transgenic mouse model in correlation to the pathological load. To validate its value for therapy development, we show target engagement of the drug candidate anle138b in the brain tissues from αSYN(A30P) mouse and multiple system atrophy as well as in vivo in αSYN fibril-injected rats. Finally, our translational approach in a first-in-human patient with clinically established MSA, revealed a marked tracer binding in regions affected by αSYN pathology, particularly in the striatum, where the pattern corresponded with the neurodegeneration shown by dopamine transporter single-photon emission computed tomography.
Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma
2024-03-20

Abstract Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next‐generation immunotherapies including T‐cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; n = 32), adult melanoma (&gt;30 years, n = 30), and benign melanocytic nevi in children (0–18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression &gt;75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age‐dependent expression could be observed. An analysis of event‐free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor‐associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age‐dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.
A Rational Trade-Off Between the Costs and Benefits of Automatic and Controlled Processing
2024-03-20

The Stroop effect suggests that humans arbitrate between automatic and controlled processing. Previous work argues that this arbitration reflects a cost-benefit analysis, weighing cognitive effort against performance. However, it is unclear how these costs and benefits can be quantified and how the trade-off between them can be performed. We present a Bayesian network model of the Stroop effect in which actions are selected by minimizing variational free energy. Based on this approach, we derive information-theoretic measures of the costs and benefits of both automatic and controlled processing and show that minimizing free energy optimizes the trade-off between them. Furthermore, we demonstrate that the so-called congruency and proportion congruency effects in the Stroop task are the result of this optimization, in an environment that contains specific statistical regularities. Thereby, we provide an explicit account of when and how much automatic and controlled processing should be expected under a rational trade-off.
Context memory formed in medial prefrontal cortex during infancy enhances learning in adulthood
2024-03-20

Abstract Adult behavior is commonly thought to be shaped by early-life experience, although episodes experienced during infancy appear to be forgotten. Exposing male rats during infancy to discrete spatial experience we show that these rats in adulthood are significantly better at forming a spatial memory than control rats without such infantile experience. We moreover show that the adult rats’ improved spatial memory capability is mainly based on memory for context information during the infantile experiences. Infantile spatial experience increased c-Fos activity at memory testing during adulthood in the prelimbic medial prefrontal cortex (mPFC), but not in the hippocampus. Inhibiting prelimbic mPFC at testing during adulthood abolished the enhancing effect of infantile spatial experience on learning. Adult spatial memory capability only benefitted from spatial experience occurring during the sensitive period of infancy, but not when occurring later during childhood, and when sleep followed the infantile experience. In conclusion, the infantile brain, by a sleep-dependent mechanism, favors consolidation of memory for the context in which episodes are experienced. These representations comprise mPFC regions and context-dependently facilitate learning in adulthood.
Patients with systemic sclerosis and low CD4 numbers after autologous stem cell transplantation have a favorable outcome
2024-03-20

Abstract Background Treatment with high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (aHSCT) is an intensive treatment option for patients with severe forms of systemic sclerosis (SSc). Even though associated with a high treatment related mortality, the results in this high-risk population are generally favourable. The knowledge on the potential mechanism of action of this therapy and how it can improve patients with SSc is crucial to better select the right patients for aHSCT. Methods This is a monocentric retrospective study from Tübingen, Germany, including 32 patients who underwent aHSCT. Peripheral blood samples were analysed for different lymphocyte subsets at various timepoints before and after aHSCT. Patients were divided into responders and non-responders according to the modified Rodnan skin score and lung function test in the three years following aHSCT. Results Responders showed significantly lower levels of cluster of differentiation (CD)4 positive T cells in the first months after aHSCT (month 1 and 3), B cells (month 3 and 6 after aHSCT) and natural killer cells (month 1). Mantel-cox test showed a significant deviation of the probability curves, i.e. patients with lower CD4 + T cells and natural killer cells one month and B cells after 3 months after stem cell transplantation had a higher probability to belong to the responder group. Conclusions Taken together, this study supports the theory that a profound CD4 + T cell and B cell lymphopenia is important for patients with SSc to achieve a sustained response after aHSCT.
Demonstrating Prebiotic Peptide Evolution by Nitrogen Isotope Discrimination in an Autocatalytic Chemical Reaction Network
2024-03-20

Nitrogen isotope discrimination may be closely related to the prebiotic evolution of peptides that occurred in the origin of life from chemical reaction networks (CRNs). We deduce that autocatalytic Sammox (sulfurous reduction coupled to anaerobic ammonium oxidation)-driven CRN is a feasible scenario for life origin. To demonstrate prebiotic peptide evolution, we investigated N isotope discrimination in proteinogenic amino acids and peptide synthesis in Sammox-driven CRNs, combining mathematical and physical models. The species and amounts of proteinogenic amino acids generated in Sammox-driven CRNs with 14NH4+ as the N source were all significantly higher than those in Sammox-driven CRNs with 15NH4+ as the N source for both hydrothermal and microaerobic eutectic freezing conditions. The low yield of 15N-amino acids, both species and amounts, will lead to the formation of 15N-peptides with poor structure and function and slow peptide dynamics; these peptides might be preferentially degraded in Sammox-driven CRNs. We then explored the nitrogen isotopic effects during the synthesis process from ammonia to glycine, from glycine to glycine-containing peptides, and during the process of glycine-containing peptide hydrolysis. 15N are eliminated in competition with 14N during the process of glycine synthesis, glycine-containing peptide synthesis, and glycine-containing peptide hydrolysis under hydrothermal conditions as determined by the maximum entropy production principle, which is a prebiotic evolution process. In addition, pyrrole as the building block of the prosthetic group, which is generated from Sammox-driven CRNs under hydrothermal conditions, may provide a more evolutionary possibility of prebiotic peptides.
Theta transcranial alternating current stimulation is not effective in improving working memory performance
2024-03-20

Abstract There is an extensive body of research showing a significant relationship between frontal midline theta activity in the 4-8 Hz range and working memory (WM) performance. Transcranial alternating current stimulation (tACS) is recognized for inducing lasting changes in brain oscillatory activity. Across two experiments, we tested whether WM could be improved through tACS of dorsomedial prefrontal cortex and anterior cingulate cortex, by affecting executive control networks associated with frontal midline theta. In Experiment 1, following either a 20-minute verum or sham stimulation applied to Fpz-CPz at 1 mA and 6 Hz, 31 participants performed WM tasks, while EEG was recorded. The tasks required participants to either mentally manipulate memory items or retain them in memory as they were originally presented. No significant effects were observed in behavioral performance, and we found no change in theta activity during rest and task following stimulation. However, alpha activity during retention or manipulation of information in WM was less strongly enhanced during the delay period following verum stimulation as compared with sham. In Experiment 2 (N = 25), tACS was administered during the task in two separate sessions. Here, we changed the order of the stimulation blocks: a 25-minute task block was either accompanied first by sham stimulation and then by verum stimulation, or vice versa. Again, we found no improvements in WM through either tACS after-effects or online stimulation. Taken together, our results demonstrate that theta frequency tACS applied at the midline is not an effective method for enhancing WM.
Leveling up fun: Learning progress, expectations, and success influence enjoyment in video games
2024-03-20

What factors influence how much fun people have when engaging in inherently enjoyable tasks? The theory of learning progress predicts that people will have the most fun in environments of intermediate difficulty because these environments offer the most progress in learning about the world. Past studies have frequently focused on simple experimental paradigms in which learning was still instrumental for later tasks. Here, we put the theory of fun as learning progress to a test in three large and realistic video game data sets: a puzzle game (with 7,994 levels and 376,341 votes), a racing game (138,662 levels and 614,770 votes), and a platformer game (115,032 levels and 795,313 votes). As predicted, people preferred levels of intermediate difficulty in all games. Yet, additional factors influencing people's enjoyment also emerged: players preferred levels that matched closely with their prior expectations of difficulty and were also motivated by success. We further confirmed these factors in two precisely controlled experiments. Taken together, these results advance our understanding of the dynamics of fun in realistic environments and emphasize the importance of using both realistic, game-like environments and highly controlled experiments to refine theories of human learning and decision-making.
Influence of Different Sample Preparation Approaches on Proteoform Identification by Top-Down Proteomics
2024-03-20

Abstract Top-down proteomics (TDP) has seen significant advances in the past, and a plethora of sample preparation workflows have been developed. Here, we systematically investigated the influence of different sample preparation steps on proteoform and protein identifications, including cell lysis, reduction and alkylation, proteoform enrichment, purification, and fractionation. We found that all steps in sample preparation influence the subset of proteoforms identified (e.g., their number, confidence, physicochemical properties, and artificially generated modifications). The various sample preparation strategies resulted in complementary identifications, significantly increasing the proteome coverage. Overall, 13,975 proteoforms from 2,720 proteins of human Caco-2 cells were identified. The results presented can serve as suggestions for designing and adapting TDP sample preparation strategies to particular research questions. Moreover, the sampling bias and modifications identified at the intact protein level will also be useful in improving bottom-up proteomics approaches.
Increased safety in periodontal surgery: Doppler ultrasound for detection of relevant palatal blood vessels—A proof‐of‐concept and cross‐sectional study
2024-03-20

Abstract Aim To evaluate the suitability of a Doppler ultrasound probe in detecting the greater palatine artery or its greater branches non‐invasively. Materials and Methods The palatal mucosa of 108 participants (median age 34 years, 51 female) was systematically divided into transversal sectors, each aligning with the positions of the upper molars (M), premolars (P) and canine teeth (C), aiming to facilitate precise and consistent localization of the detected palatal blood vessel across different patients. Blood flow of the palatal blood vessels, presumably, was located by scanning the palatal vault bilaterally using an 8‐MHz ultrasound probe linked to a transducer. The distance to the corresponding tooth was measured using a millimetre‐scale periodontal probe. Results Within the regions of M2 to P1, the ultrasound transducer gave a delimitable acoustic pulse signal in 80%–98% of all measurements. The measured median distances between the determined position of the artery and the corresponding teeth ranged from 13 to 15 mm, with smaller distances in the anterior region. In several sectors, the distance was significantly higher for men (C: p = .048; P1: p = .041, M1: p &lt; .01; M2: p = .034). Conclusions Use of the Doppler ultrasound transducer might be a promising approach to non‐invasively detect relevant palatine blood vessels preoperatively. It, therefore, might have the potential to reduce the risk of accidental injury during palatal surgery.
Characterization of the Pristionchus pacificus “epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2
2024-03-21

Abstract Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation—or lack thereof—of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the “epigenetic toolkit” available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.
Voluntary E-Learning Exercises Support Students in Mastering Statistics
2024-03-21

Abstract University students often learn statistics in large classes, and in such learning environments, students face an exceptionally high risk of failure. One reason for this is students’ frequent statistics anxiety. This study shows how students can be supported using e-learning exercises with automated knowledge of correct response feedback, supplementing a face-to-face lecture. To this end, we surveyed 67 undergraduate social science students at a German university and observed their weekly e-learning exercises. We aggregated students’ exercise behavior throughout the semester to explain their exam performance. To control for participation bias, we included essential predictors of educational success, such as prior achievement, motivation, personality traits, time preferences, and goals. We applied a double selection procedure based on the machine learning method Elastic Net to include an optimal but sparse set of control variables. The e-learning exercises indirectly promoted the self-regulated learning techniques of retrieval practice and spacing and provided corrective feedback. Working on the e-learning exercises increased students’ performance on the final exam, even after controlling for the rich set of control variables. Two-thirds of students used our designed e-learning exercises; however, only a fraction of students spaced out the exercises, although students who completed the exercises during the semester and were not cramming at the end benefited additionally. Finally, we discuss how the results of our study inform the literature on retrieval practice, spacing, feedback, and e-learning in higher education.
New GATE Digitizer Unit for versions post v9.3
2024-03-21

The Digitizer Unit plays an important role in modeling using Geant4 Application for Tomographic Emission (GATE), a Geant4-based platform used for numerical simulations in medical imaging and radiotherapy. It simulates the response of the photodetection components using a sequence of analytical and semi-analytical models. The Digitizer Unit was written for the first version of GATE approximately 20 years ago. Since then, it has in parts grown in a code that can be hardly maintained. Some parts of the code were unused or duplicated; some of the functionalities were not working anymore. Therefore, the GATE Digitizer Unit update is required in order to incorporate the novelties of Geant4 to update its current version and add new features. In this article, the implementation of the new GATE Digitizer Unit (since version 9.3) is presented. Added functionalities, the impact of changes on users, the current status of the work, and perspectives are discussed.
Compilation and Validation of Two Short Forms to Measure HEXACO Dimensions in Elementary School Children
2024-03-21

Personality trait measures for children are rarely based on the HEXACO Model of Personality, although research using this framework could provide important insights into the structure and development of children's personalities. There is no HEXACO measure for elementary school children to date, and existing measures for older children seem inappropriate for this age group (e.g., due to some item content). We thus compiled two HEXACO-based short forms for measuring personality in elementary school children (8-10 years old) via parent reports. We applied a meta-heuristic item sampling algorithm (Ant Colony Optimization) in a training sample with 1,641 parent reports of 122 administered items. We selected a 54-Item Short Form comprising a latent facet structure and an 18-Item Ultra-Short Form comprising a correlated factors model for all six HEXACO dimensions but no facet structure. Both short forms showed good model fit in a holdout sample (n = 411) and sufficiently high re-test correlations after six months. Convergent and divergent validities for maximal performance measures and socio-emotional constructs (also measured six months after the initial personality assessment) were largely in line with theoretical assumptions. Overall, our study provides support for construct, re-test, and (predictive) criterion validity for the selected short forms.