julilili42/papers huggingface dataset:
Really? It depends! How authentic learning material affects involvement with personal stories of the past
2024-05-16

Authentic learning is believed to possess qualities that boost student motivation and learning. However, prior studies have not consistently found the assumed positive effects of authentic learning, thus highlighting the need to better understand the underlying learning processes. We examined effects of authentic learning material on learners' involvement and different facets of the perceived authenticity of the material. Participants were 336 adults. We conducted an experimental online study with three conditions varying in the framing of their authenticity. We presented videos in which people talked about their experiences in war and daily life in the past, and we labeled these clips eyewitness accounts, eyewitness accounts played by actors, or reconstructed accounts played by actors. Participants were randomly assigned. Results indicated that treatment condition particularly affected participants' emotional involvement with the story and that, in particular, one facet of perceived authenticity (Vividness of History) predicted learners' involvement. The study adds to the research field of authentic learning in general, and learning with personal stories of the past in particular, by addressing involvement processes and examining different facets of perceived authenticity.
Executive function deficits in genetic frontotemporal dementia: results from the GENFI study
2024-05-16

Abstract Background Executive dysfunction is a core feature of frontotemporal dementia (FTD). Whilst there has been extensive research into such impairments in sporadic FTD, there has been little research in the familial forms. Methods 752 individuals were recruited in total: 214 C9orf72 , 205 GRN and 86 MAPT mutation carriers, stratified into asymptomatic, prodromal and fully symptomatic, and 247 mutation negative controls. Attention and executive function were measured using the Weschler Memory Scale-Revised (WMS-R) Digit Span Backwards (DSB), the Wechsler Adult Intelligence Scale-Revised Digit Symbol task, the Trail Making Test Parts A and B, the Delis-Kaplan Executive Function System Color Word Interference Test and verbal fluency tasks (letter and category). Linear regression models with bootstrapping were used to assess differences between groups. Correlation of task score with disease severity was also performed, as well an analysis of the neuroanatomical correlates of each task. Results Fully symptomatic C9orf72, GRN and MAPT mutation carriers were significantly impaired on all tasks compared with controls (all p&lt;0.001), except on the WMS-R DSB in the MAPT mutation carriers (p=0.147). Whilst asymptomatic and prodromal C9orf72 individuals also demonstrated deficits compared with controls, neither the GRN or MAPT asymptomatic or prodromal mutation carriers showed significant differences. All tasks significantly correlated with disease severity in each of the genetic groups (all p&lt;0.001). Conclusions Individuals with C9orf72 mutations show difficulties with executive function from very early on in the disease and this continues to deteriorate with disease severity. In contrast, similar difficulties occur only in the later stages of the disease in GRN and MAPT mutation carriers. This differential performance across the genetic groups will be important in neuropsychological task selection in upcoming clinical trials.
How Much Retrieval Ability Is in Originality?
2024-05-17

ABSTRACT Creative fluency and originality are pivotal indicators of creative potential. Both have been embedded in hierarchical intelligence models as part of the ability to retrieve information from long‐term memory; an ability that is often measured with indicators of retrieval fluency. Creative fluency and retrieval fluency, both expressed by the count of correct responses, are procedurally highly similar. This raises the question how creative fluency and originality are related with retrieval fluency and how both are predicted by other cognitive abilities. In a multivariate study ( N = 320), we found that retrieval fluency is very strongly related with creative fluency ( r = .87) and substantially related with originality ( r = .59). A combined fluency factor still fitted the data well. Cognitive abilities accounted for 63% variance in fluency and 47% variance in originality. After controlling for established cognitive abilities, latent variables for fluency and originality were unrelated with one another. This suggests that the procedural proximity of the ability to fluently generate either information from long‐term memory or ad‐hoc solutions to unusual tasks and the ability to come up with original ideas needs reconsideration. Locating originality below an overarching retrieval factor is contradicted by the present data.
The effects of intermittent theta burst stimulation over dorsal premotor cortex on primary motor cortex plasticity in young and older adults
2024-05-17

Abstract Previous transcranial magnetic stimulation (TMS) research suggests that the dorsal premotor cortex (PMd) influences neuroplasticity within the primary motor cortex (M1) through indirect (I) wave interneuronal circuits. However, it is unclear how the influence of PMd on the plasticity of M1 I‐waves changes with advancing age. This study therefore investigated the neuroplastic effects of intermittent theta burst stimulation (iTBS) to M1 early and late I‐wave circuits when preceded by iTBS (PMd iTBS‐M1 iTBS) or sham stimulation (PMd sham‐M1 iTBS) to PMd in 15 young and 16 older adults. M1 excitability was assessed with motor evoked potentials (MEP) recorded from the right first dorsal interosseous using posterior–anterior (PA) and anterior–posterior (AP) current TMS at standard stimulation intensities (PA 1mV , AP 1mV ) and reduced stimulation intensities (PA 0.5mV , early I‐waves; AP 0.5mV , late I‐waves). PMd iTBS‐M1 iTBS lowered the expected facilitation of PA 0.5mV (to M1 iTBS) in young and older adults ( P = 0.009), whereas the intervention had no effect on AP 0.5mV facilitation in either group ( P = 0.305). The modulation of PA 0.5mV following PMd iTBS‐M1 iTBS may reflect a specific influence of PMd on different I‐wave circuits that are involved in M1 plasticity within young and older adults.
Photon Pressure with an Effective Negative Mass Microwave Mode
2024-05-17

Harmonic oscillators belong to the most fundamental concepts in physics and are central to many current research fields such as circuit QED, cavity optomechanics, and photon pressure systems. Here, we engineer a microwave mode in a superconducting LC circuit that mimics the dynamics of a negative mass oscillator, and couple it via photon pressure to a second low-frequency circuit. We demonstrate that the effective negative mass dynamics lead to an inversion of dynamical backaction and to sideband cooling of the low-frequency circuit by a blue-detuned pump field, which can be intuitively understood by the inverted energy ladder of a negative mass oscillator.
Mutant dominant-negative rhodopsin∆I256 causes protein aggregates degraded via ERAD and prevents normal rhodopsin from proper membrane trafficking
2024-05-17

Dominant mutations in the rhodopsin gene ( Rho ) contribute to 25% of autosomal dominant retinitis pigmentosa (adRP), characterized by photoreceptor loss and progressive blindness. One such mutation, Rho ∆I256 , carries a 3-bp deletion, resulting in the loss of one of two isoleucines at codons 255 and 256. Our investigation, using recombinant expression in HEK293 and COS-7 cells, revealed that Rho ∆ I256 , akin to the known adRP mutation Rho P23H , induces the formation of rhodopsin protein (RHO) aggregates at the perinuclear region. Co-expression of Rho ∆I256 or Rho P23H with wild-type Rho WT , mimicking the heterozygous genotype of adRP patients, demonstrated the dominant-negative effect, as all isoforms were retained in perinuclear aggregates, impeding membrane trafficking. In retinal explants from WT mice, mislocalization of labeled adRP isoforms at the outer nuclear layer was observed. Further analysis revealed that RHO ∆I256 aggregates are retained at the endoplasmic reticulum (ER), undergo ER-associated degradation (ERAD), and colocalize with the AAA-ATPase escort chaperone valosin-containing protein (VCP). These aggregates are polyubiquitinated and partially colocalized with the 20S proteasome subunit beta-5 (PSMB5). Pharmacological inhibition of proteasome- or VCP activity increased RHO ∆I256 aggregate size. In summary, RHO ∆I256 exhibits dominant pathogenicity by sequestering normal RHO WT in ER aggregates, preventing its membrane trafficking and following the ERAD degradation.
Suppression PCR-Based Selective Enrichment Sequencing for Pathogen and Antimicrobial Resistance Detection on Cell-Free DNA in Sepsis—A Targeted, Blood Culture-Independent Approach for Rapid Pathogen and Resistance Diagnostics in Septic Patients
2024-05-17

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. The rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcomes in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we targeted eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested in an experimental research study on the first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be additionally detected. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time-to-results to 11–13 h and suggesting diagnostic potential in sepsis.
Integrated combinatorial functional genomics and spatial transcriptomics of tumors decodes genotype to phenotype relationships
2024-05-17

ABSTRACT Linking the complex genetic changes underlying cancer to relevant disease-phenotypes poses a challenge. Therefore, we present CHOCOLAT-G2P, a scalable approach that integrates multiplex in vivo functional genomics with spatial transcriptomics. By redeploying RNA-templated ligation probes of commercial spatial transcriptomics technology, we streamline mapping composite genetic alterations and transcriptome-wide phenotyping on the same tissue section on a single readout platform. Using this framework, we studied combinatorial effects of 8 perturbations that induce autochthonous mosaic liver tumors sampled from 256 genotypes. Interrogating 324 tumors across six ∼6×6 mm 2 sections, we charted phenotypic landscapes of genotypically-defined tumor ecosystems, revealing zonation-associated hepatocellular carcinoma subclasses and associations between tumor subtypes and stromal-as well as immune-cell signatures. Further, we decoded epistasis within compound genotypes uncovering opposing roles of Vegfa and mutant Ctnnb1 to cholangiocarcinoma development. Thus, CHOCOLAT-G2P lays a foundation to decipher how combinations of alterations interact to reprogram tumor cells and their microenvironment within the holistic context of tissue and whole organisms. ( https://chocolat-g2p.dkfz.de/ ).
The Jojosi Dongas: An interdisciplinary project to study the evolution of human behaviour and landscapes in open-air contexts
2024-05-17

Hunter-gatherer groups conduct most of their activities in open landscapes as they provide drinking water, food, and raw materials, and offer spaces for social gatherings. The remains left behind at such sites allow for unique archaeological insights into the spatial patterning of prehistoric behaviour. The Stone Age record in southern Africa remains best-known from sheltered sites. A paucity of stratified open-air localities precludes understanding the full spectrum of past hominin activities. Here we introduce an interdisciplinary project in KwaZulu-Natal to study the evolution of human behaviour and landscape dynamics during the Pleistocene in the open-air context of a stratified hillslope with sediments exposed in so-called dongas, a landform created by gully erosion. The project encompasses field and laboratory approaches, combining archaeological, geographical, geological, chronometric, and palaeoenvironmental data. After reviewing relevant open-air research in archaeology and geography, we identify the Jojosi Dongas as a promising research area. Our fieldwork results from 2022-2023 demonstrate the high archaeological, geographical, and geological potential of this landscape. Foot surveys found abundant MSA artefacts spread throughout the dongas, one area with ESA tools, but little to no traces of LSA or later material. Most finds lie on the surface with rarer stratified material occurring in exposed profiles. The surface MSA material is characterised by almost exclusive hornfels use, frequent cortical pieces, many large blanks and cores, and rare retouched tools. These features differ markedly from lithic trends observed in well-known shelter sites, likely the result of differences in site function. Based on the nature of the surface assemblages and the presence of a large outcrop of high-quality hornfels, we hypothesise that the Jojosi Dongas may have been a specialised quarry and workshop area. The stratified MSA occupations are the focus of ongoing excavations and further studies will aim to test our preliminary interpretations provided here.
Decoding ruminative states from neurophysiological patterns
2024-05-17

Abstract Individuals with depression often engage in iterative “rumination” about challenging situations and potential outcomes. Although the state of rumination has been associated with diverse univariate neurophysiological features, the potential to use multivariate patterns to decode it remains uncertain. In this study, we trained linear support vector machines to differentiate state rumination from distraction using patterns in the alpha, beta, and theta bands, as well as inter-channel connectivity. We used validated tasks to induce rumination or distraction for eight minutes in 24 depressed individuals in six runs over three sessions. During inductions, we recorded 64-channel EEG data and measured self-reported levels of rumination. Participants reported strongly increased rumination, and we decoded state rumination from EEG patterns with significant accuracy. However, the informative features were not consistent across participants, demonstrating that while ruminative states can indeed be decoded from EEG data, these states appear to reflect processes unique to each individual.
Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study
2024-05-18

Abstract The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham ( p = 0.039) and cathodal net-tDCS ( p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation ( p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.
Exploring ‘decision regret’ in adjuvant‐treated melanoma patients: Results from a cross‐sectional survey on 200 participants
2024-05-19

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. This study was approved by the Ethics Commission of the Eberhard Karls University Tuebingen with the number 174/2023BO2 and was conducted in accordance with consensus ethical principles derived from international ethical guidelines, including the Declaration of Helsinki.
Polygenic Risk Scores Validated in Patient‐Derived Cells Stratify for Mitochondrial Subtypes of Parkinson's Disease
2024-05-20

Objective The aim of our study is to better understand the genetic architecture and pathological mechanisms underlying neurodegeneration in idiopathic Parkinson's disease (iPD). We hypothesized that a fraction of iPD patients may harbor a combination of common variants in nuclear‐encoded mitochondrial genes ultimately resulting in neurodegeneration. Methods We used mitochondria‐specific polygenic risk scores (mitoPRSs) and created pathway‐specific mitoPRSs using genotype data from different iPD case–control datasets worldwide, including the Luxembourg Parkinson's Study (412 iPD patients and 576 healthy controls) and COURAGE‐PD cohorts (7,270 iPD cases and 6,819 healthy controls). Cellular models from individuals stratified according to the most significant mitoPRS were subsequently used to characterize different aspects of mitochondrial function. Results Common variants in genes regulating Oxidative Phosphorylation (OXPHOS ‐PRS ) were significantly associated with a higher PD risk in independent cohorts (Luxembourg Parkinson's Study odds ratio, OR = 1.31[1.14–1.50], p ‐value = 5.4e‐04; COURAGE‐PD OR = 1.23[1.18–1.27], p ‐value = 1.5e‐29). Functional analyses in fibroblasts and induced pluripotent stem cells‐derived neuronal progenitors revealed significant differences in mitochondrial respiration between iPD patients with high or low OXPHOS ‐PRS ( p ‐values &lt; 0.05). Clinically, iPD patients with high OXPHOS ‐PRS have a significantly earlier age at disease onset compared to low‐risk patients (false discovery rate [FDR]‐adj p ‐value = 0.015), similar to prototypic monogenic forms of PD. Finally, iPD patients with high OXPHOS ‐PRS responded more effectively to treatment with mitochondrially active ursodeoxycholic acid. Interpretation OXPHOS ‐PRS may provide a precision medicine tool to stratify iPD patients into a pathogenic subgroup genetically defined by specific mitochondrial impairment, making these individuals eligible for future intelligent clinical trial designs. ANN NEUROL 2024;96:133–149
Challenging the safety and efficacy of topically applied chlorogenic acid, apigenin, kaempferol, and naringenin by HET-CAM, HPLC-TBARS-EVSC, and laser Doppler flowmetry
2024-05-20

The integumentary system, a vital organ, constitutes a multifaceted barrier against pathogens and environmental factors, crucial for maintaining homeostasis. Intrinsic and extrinsic factors can accelerate skin aging and compromise its homeostatic functions and solar rays, particularly ultraviolet (UV) radiation, pose a significant risk for skin cancer. Polyphenols are molecules that donate hydrogen or electrons, preventing the oxidation of substances, such as lipids, or the formation of inflammatory mediators by cyclooxygenase enzymes. This study explored the in vitro safety, by HET-CAM (hen’s egg test on chorioallantoic membrane), and protective effects of polyphenols (chlorogenic acid, apigenin, kaempferol, and naringenin) against stratum corneum UV-induced lipid peroxidation using an innovative method, the HPLC-TBARS-EVSC (high-performance liquid chromatography–thiobarbituric acid reactive substances– ex vivo stratum corneum), and a stress test using methyl nicotinate and laser Doppler flowmetry to establish in vivo the samples’ topical anti-inflammatory ability. An aqueous gel containing 0.1% w / w of each polyphenol was formulated using ammonium acryloyldimethyltaurate/VP copolymer. Through the utilization of the HET-CAM assay for in vitro safety assessment, chlorogenic acid, apigenin, kaempferol, and naringenin were classified as non-irritating active ingredients. This classification was based on their lack of adverse reactions within the vascularization of the chorioallantoic membrane. To assess the protective capabilities of four polyphenols against lipid peroxidation in the stratum corneum, the HPLC-TBARS-EVSC protocol was conducted. It was observed that only naringenin exhibited a significant reduction in epidermal lipoperoxidation, indicating superior anti-radical potential. Conversely, chlorogenic acid, apigenin, and kaempferol displayed a pro-oxidant profile under the specified test conditions. The laser Doppler flowmetry suggested the anti-inflammatory potential of naringenin, kaempferol, and chlorogenic acid, with naringenin showing superior efficacy involving all parameters quantified. Naringenin emerged as the only polyphenol capable of reducing the intensity of the inflammatory response induced by methyl nicotinate solution in the participants, compared to the blank gel and the untreated area. This comprehensive investigation underscores the diverse protective roles of polyphenols in skin health, emphasizing naringenin’s notable anti-radical and anti-inflammatory properties.
Finding universal relations using statistical data analysis
2024-05-20

We present applications of statistical data analysis methods from both bivariate and multivariate statistics to find suitable sets of neutron star features that can be leveraged for accurate and equation of state independent---or universal---relations. To this end, we investigate the ability of various correlation measures such as distance correlation and mutual information in identifying universally related pairs of neutron star features. We also evaluate relations produced by methods of multivariate statistics such as principal component analysis to assess their suitability for producing universal relations with multiple independent variables. As part of our analyses, we also put forward multiple entirely novel relations, including a multivariate relation for the -mode frequency of neutron stars with a reduced average relative error of 0.010, compared to an error of 0.015 of existing, bivariate relations.