Miracle-dz/UniFAR-FTUs huggingface dataset:
Stay on Course in VR: Comparing the Precision of Movement between Gamepad, Armswinger, and Treadmill: Kurs halten in VR: Vergleich der Bewegungspräzision von Gamepad, Armswinger und Laufstall

In diesem Beitrag wird untersucht, inwieweit verschiedene Formen von Fortbewegungstechniken in Virtual Reality Umgebungen Einfluss auf die Präzision bei der Interaktion haben. Dabei wurden insgesamt drei Techniken untersucht: Zwei der Techniken integrieren dabei eine körperliche Aktivität, um einen hohen Grad an Realismus in der Bewegung zu erzeugen (Armswinger, Laufstall). Als dritte Technik wurde ein Gamepad als Baseline herangezogen. In einer Studie mit 18 Proband:innen wurde die Präzision dieser drei Fortbewegungstechniken über sechs unterschiedliche Hindernisse in einem VR-Parcours untersucht. Die Ergebnisse zeigen, dass für einzelne Hindernisse, die zum einen eine Kombination aus Vorwärts- und Seitwärtsbewegung erfordern (Slalom, Klippe) sowie auf Geschwindigkeit abzielen (Schiene), der Laufstall eine signifikant präzisere Steuerung ermöglicht als der Armswinger. Auf den gesamten Parcours gesehen ist jedoch kein Eingabegerät signifikant präziser als ein anderes. Die Benutzung des Laufstalls benötigt zudem signifikant mehr Zeit als Gamepad und Armswinger. Ebenso zeigte sich, dass das Ziel, eine reale Laufbewegung 1:1 abzubilden, auch mit einem Laufstall nach wie vor nicht erreicht wird, die Bewegung aber dennoch als intuitiv und immersiv wahrgenommen wird.
Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis

A prevalent feature of Strongyloides stercoralis is a life-long and potentially lethal infection that is due to the nematode parasite’s ability to autoinfect and, thereby, self-replicate within its host. Here, we investigated the role of the parasite’s nuclear receptor, Ss-DAF-12, in governing infection. We identified Δ7-DA as the endogenous Ss-DAF-12 ligand and elucidated the hormone’s biosynthetic pathway. Genetic loss of function of the ligand’s rate-limiting enzyme demonstrated that Δ7-DA synthesis is necessary for parasite reproduction, whereas its absence is required for development of infectious larvae. Availability of the ligand permits Ss-DAF-12 to function as an on/off switch governing autoinfection, making it vulnerable to therapeutic intervention. In a preclinical model of hyperinfection, pharmacologic activation of DAF-12 suppressed autoinfection and markedly reduced lethality. Moreover, when Δ7-DA was administered with ivermectin, the current but limited drug of choice for treating strongyloidiasis, the combinatorial effects of the two drugs resulted in a near cure of the disease.
Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R)

Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF.
Response of atmospheric carbon dioxide to the secular variation of weakening geomagnetic field in whole atmosphere simulations

Responses of atmospheric carbon dioxide (CO2) density to geomagnetic secular variation are investigated using the Whole Atmosphere Community Climate Model‐eXtended (WACCM‐X). Our ensemble simulations show that CO2 volume mixing ratios (VMRs) increase at high latitudes and decrease at mid and low latitudes by several ppmv in response to a 50% weakening of the geomagnetic field. Statistically significant changes in CO2 are mainly found above ~90 km altitude and primarily redetermine the energy budget at ~100‐110 km. Our analysis of transformed Eulerian mean (TEM) circulation found that CO2 change is caused by enhanced upwelling at high latitudes and downwelling at mid and low latitudes as a result of increased Joule heating. We further analyzed the atmospheric CO2 response to realistic geomagnetic weakening between 1978 and 2013, and found increasing (decreasing) CO2 VMRs at high latitudes (mid and low latitudes) accordingly. For the first time, our simulation results demonstrate that the impact of geomagnetic variation on atmospheric CO2 distribution is noticeable on a time scale of decades.
The spliced leader RNA silencing (SLS) pathway in Trypanosoma brucei is induced by perturbations of endoplasmic reticulum, Golgi, or mitochondrial proteins factors and functional analysis of SLS inducing kinase, PK3

In the parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, all mRNAs are trans-spliced to generate a common 5’ exon derived from the spliced leader RNA (SL RNA). Perturbations of protein translocation across the endoplasmic reticulum (ER) induce the spliced leader RNA silencing (SLS) pathway. SLS activation is mediated by a serine-threonine kinase, PK3, which translocates from the cytosolic face of the ER to the nucleus, where it phosphorylates the TATA binding protein TRF4, leading to the shut-off of SL RNA transcription, followed by induction of programmed cell death. Here, we demonstrate that SLS is also induced by depletion of the essential ER resident chaperones BiP and calreticulin, ER oxidoreductin 1 (ERO1), and the Golgi-localized quiescin sulfhydryl oxidase (QSOX1). Most strikingly, silencing of Rhomboid-like 1(TIMRHOM1) involved in mitochondrial protein import, also induces SLS. The PK3 kinase, which integrates SLS signals, is modified by phosphorylation on multiple sites. To determine which of the phosphorylation events activate PK3, several individual mutations or their combination were generated. These mutations failed to completely eliminate the phosphorylation or translocation of the kinase to the nucleus. The structure of PK3 kinase and its ATP binding domain were therefore modeled. A conserved phenylalanine at position 771 was proposed to interact with ATP, and the PK3F771L mutation completely eliminated phosphorylation under SLS, suggesting that the activation involves most if not all the phosphorylation sites. The study suggests that the SLS occurs broadly in response to failures in protein sorting, folding, or modification across multiple compartments.
A CRISPR-Cas assisted shotgun mutagenesis method for evolutionary genome engineering

Genome mutagenesis drives the evolution of organisms. Here, we developed a CRISPR-Cas assisted random mutation (CARM) technology for whole genome mutagenesis. The method leverages an entirely random gRNA library and SpCas9-NG to randomly damage genomes in a controllable shotgun-like manner that then triggers diverse and abundant mutations via low-fidelity repair. As a proof-of-principle, CARM was applied to evolve the capacity of Saccharomyces cerevisiae BY4741 to produce β-carotene. After seven rounds of iterative evolution over two months, a β-carotene hyper-producing strain, C7-143, was isolated with a 10.5-fold increase in β-carotene production and 857 diverse genomic mutants that comprised indels, duplications, inversions, and chromosomal rearrangements. Transcriptomic analysis revealed that the expression of 2,541 genes of strain C7-143 were significantly altered, suggesting that the metabolic landscape of the strain was deeply reconstructed. In addition, CARM was applied to evolve the industrially relevant Saccharomyces cerevisiae CEN.PK2-1C, the S-adenosyl-L-methionine production of which was increased to 2.28 times after just one round. Thus, CARM is a user-friendly and practical strategy for genetic remodeling and reverse engineering to investigate complicated organismal metabolism.
Visceral mesoderm signaling regulates assembly position and function of the Drosophila testis niche

Tissue homeostasis often requires a properly placed niche to support stem cells. Morphogenetic processes that position a niche are just being described. For the Drosophila testis we recently showed that pro niche cells, specified at disparate positions during early gonadogenesis, must assemble into one collective at the anterior of the gonad. We now find that Slit and FGF signals emanating from adjacent visceral mesoderm regulate assembly. In response to signaling, niche cells express islet, which we find is also required for niche assembly. Without signaling, niche cells specified furthest from the anterior are unable to migrate, remaining dispersed. Function of such niches is severely disrupted, with niche cells evading cell cycle quiescence, compromised in their ability to signal the incipient stem cell pool, and failing to orient stem cell divisions properly. Our work identifies both extrinsic signaling and intrinsic responses required for proper assembly and placement of the testis niche.
The Effect of Growth Medium Composition on X.campestris Metabolism in Producing Xanthan Gum

In the fermentation industry, the role of medium is very important in increasing the growth rate of microbes. Nutrient Agar (NA) is one of the common medium used for growth and increase regeneration X. campestris , while Luria-Bertani medium (LB) is usually used for matters related to X. campestris productivity in producing xanthan gum. To increase the productivity of X. campestris and xanthan gum rendement, this research used medium variation of Nutrient Broth (NB) added with mineral plus inducer and Luria-Bertani Broth (LBB) with 4% substrate of liquid sugar and 2% maize, respectively. Based on FT-IR analysis, both substrates can produce xanthan gum which qualitatively has been compatible with commercial xanthan gum. The 4% liquid sugar yielded of 34.20% - 57.88%, while 2% maize was 54.93% - 73.61%. The use of NB and LBB produced xanthan gum with viscosity of 28-31 cPs and 15-30 cPs, respectively. These viscosity values indicated that xanthan gum can be used as a thickener in its application in industry. Precipitation using a combination of salt with IPA did not provide significant changes to the xanthan gum gain. This is due to the low number of bonds between the cations of the salt and the anions of the xanthan solution.
Inflection across Categories: Tracking Abstract Morphological Processing in Language Production with MEG

Abstract Coherent language production requires that speakers adapt words to their grammatical contexts. A fundamental challenge in establishing a functional delineation of this process in the brain is that each linguistic process tends to correlate with numerous others. Our work investigated the neural basis of morphological inflection by measuring magnetoencephalography during the planning of inflected and uninflected utterances that varied across several linguistic dimensions. Results reveal increased activity in the left lateral frontotemporal cortex when inflection is planned, irrespective of phonological specification, syntactic context, or semantic type. Additional findings from univariate and connectivity analyses suggest that the brain distinguishes between different types of inflection. Specifically, planning noun and verb utterances requiring the addition of the suffix -s elicited increased activity in the ventral prefrontal cortex. A broadly distributed effect of syntactic context (verb vs. noun) was also identified. Results from representational similarity analysis indicate that this effect cannot be explained in terms of word meaning. Together, these results 1) offer evidence for a neural representation of abstract inflection that separates from other stimulus properties and 2) challenge theories that emphasize semantic content as a source of verb/noun processing differences.
An engineered CD81‐based combinatorial library for selecting recombinant binders to cell surface proteins: Laminin binding CD81 enhances cellular uptake of extracellular vesicles

Abstract The research of extracellular vesicles (EVs) has boomed in the last decade, with the promise of them functioning as target‐directed drug delivery vehicles, able to modulate proliferation, migration, differentiation, and other properties of the recipient cell that are vital for health of the host organism. To enhance the ability of their targeted delivery, we employed an intrinsically overrepresented protein, CD81, to serve for recognition of the desired target antigen. Yeast libraries displaying mutant variants of the large extracellular loop of CD81 have been selected for binders to human placental laminin as an example target. Their specific interaction with laminin was confirmed in a mammalian display system. Derived sequences were reformatted to full‐length CD81 and expressed in EVs produced by HeLa cells. These EVs were examined for the presence of the recombinant protein and were shown to exhibit an enhanced uptake into laminin‐secreting mammalian cell lines. For the best candidate, the specificity of antigen interaction was demonstrated with a competition experiment. To our knowledge, this is the first example of harnessing an EV membrane protein as mediator of de novo target antigen recognition via in vitro molecular evolution, opening horizons to a broad range of applications in various therapeutic settings.
Physician Interpretation of Data of Uncertain Clinical Utility in Oncology Prescription Drug Promotion.

BACKGROUND Little is known about how physicians interpret data displays that depict preliminary or exploratory clinical data in physician-targeted sales aids for oncology drugs. Using three factorial experiments, we examined whether disclosures of data limitations and clinical uncertainty adequately communicate the limitations and practical utility of this type of data. PARTICIPANTS AND METHODS The studies used a 2 (disclosure of data limitations: technical, nontechnical) × 2 (disclosure of clinical uncertainty: present, absent) + 1 (control: no disclosure) between-subjects experimental design to examine the impact of disclosures as they relate to presentations of preliminary or exploratory data in promotional communications for oncology products. In each experiment, we randomized oncologists and primary care physicians with oncology experience to view one version of a 2-page sales aid. Following this exposure, physicians completed a web-based survey. The design was replicated in three concurrently conducted experiments using sales aids for different fictitious oncology drugs, each featuring one of three common data displays: a forest plot (N = 495), a Kaplan-Meier curve (N = 504), or a bar chart (N = 532). RESULTS Results provide initial evidence that in some contexts disclosures can improve understanding of the clinical utility of certain information about a drug and the limitations of results presented in a data display. Disclosures can also temper perceptions of how much evidence is presented that supports a conclusion that the drug is an appropriate treatment. In terms of the language used in the disclosure of data limitations, physicians in all three experiments strongly preferred the non-technical disclosures. CONCLUSION The findings from the three experiments in this study suggest that disclosures have the potential to increase relevant knowledge, but more research is needed to establish best practice recommendations for using disclosures to convey contextual information relevant for interpreting data displays in promotional communications. IMPLICATIONS FOR PRACTICE Our manuscript reports the results from three large, online experimental studies that address a growing concern that drug companies often share favorable clinical trial results with physicians in promotional materials that lack important context for physicians to interpret the data. Our series of studies investigates whether strategic use of two types of disclosures (disclosure of data limitations and a disclosure of clinical uncertainty) improve understanding and reduce misinterpretations among physicians. The results from these studies help identify communication factors that impact how physicians critically appraise preliminary or exploratory clinical trial data to inform policy and regulatory efforts.
Decreased Serum Level of Interleukin-22 Correlates with Hepcidin in Patients with Hidradenitis Suppurativa

Current understanding of the underlying pathophysiology of hidradenitis suppurativa (HS) links the disease with proinflammatory activation and autoimmune processes. This study investigated serum levels of interleukin (IL)-22, a cytokine critically involved in epithelial homeostasis, in the context of the broad clinical spectrum of patients with HS. The study also assessed the relationship between serum IL-22 and pro-inflammatory activation (as evidenced by serum level of IL-6) and serum hepcidin (central regulator of systemic iron homeostasis). Serum concentrations of IL-22 were assessed in 74 patients with HS and 15 healthy subjects. Compared with healthy controls, patients with HS demonstrated decreased levels of serum IL-22 (median; interquartile range (IQR): 12.4 pg/ml (9.8; 23.5) vs 34.8 pg/ml (24.8; 39.8), p < 0.001 vs controls). Disease severity (assessed both with Hurley staging and Hidradenitis Suppurativa Severity Index) did not differentiate IL-22 levels (p > 0.1 in both comparisons). Serum levels of IL-22 and IL-6 did not correlate with each other (R=–0.17, p = ns). In a subgroup of 24 patients with HS with pro-inflammatory activation, the mean level of IL-22 was similar to that of the remaining patients (median (IQR): 9.8 pg/ml (8.5; 15.0) vs 12.0 pg/ml (9.4; 16.3), p = ns). Patients with HS demonstrated a decreased level of hepcidin (mean: 31.3 ± 25.9 pg/ml), which correlated with the levels of IL-22 (R=0.36, p < 0.05). Patients with HS demonstrated significantly decreased levels of serum IL-22, which was neither correlated with pro-inflammatory status nor associated with disease severity, but correlated modestly with serum hepcidin.
Outer Retinal Layer Thickness Changes in White Matter Hyperintensity and Parkinson's Disease

Purpose: To investigate the thickness changes of outer retinal layers in subjects with white matter hyperintensities (WMH) and Parkinson's Disease (PD). Methods: 56 eyes from 31 patients with WMH, 11 eyes from 6 PD patients, and 58 eyes from 32 healthy controls (HC) were enrolled in this study. A macular-centered scan was conducted on each participant using a spectral-domain optical coherence tomography (SD-OCT) device. After speckle noise reduction, a state-of-the-art deep learning method (i.e., a context encoder network) was employed to segment the outer retinal layers from OCT B-scans. Thickness quantification of the outer retinal layers was conducted on the basis of the segmentation results. Results: WMH patients had significantly thinner Henle fiber layers, outer nuclear layers (HFL+ONL) and photoreceptor outer segments (OS) than HC (p = 0.031, and p = 0.005), while PD patients showed a significant increase of mean thickness in the interdigitation zone and the retinal pigment epithelium/Bruch complex (IZ+RPE) (19.619 ± 4.626) compared to HC (17.434 ± 1.664). There were no significant differences in the thickness of the outer plexiform layer (OPL), the myoid and ellipsoid zone (MEZ), and the IZ+RPE layer between WMH and HC subjects. Similarly, there were also no obvious differences in the thickness of the OPL, HFL+ONL, MEZ and the OS layer between PD and HC subjects. Conclusion: Thickness changes in HFL+ONL, OS, and IZ+RPE layers may correlate with brain-related diseases such as WMH and PD. Further longitudinal study is needed to confirm HFL+ONL/OS/IZ+RPE layer thickness as potential biomarkers for detecting certain brain-related diseases.
Interactions between dietary flavonoids and the gut microbiome: a comprehensive review

Abstract Flavonoids are natural polyphenol secondary metabolites that are widely produced in planta. Flavonoids are ubiquities in human dietary intake and exhibit a myriad of health benefits. Flavonoids-induced biological activities are strongly influenced by their in situ availability in the human GI tract, as well as the levels of which are modulated by interaction with the gut bacteria. As such, assessing flavonoids–microbiome interactions is considered a key to understand their physiological activities. Here, we review the interaction between the various classes of dietary flavonoids (flavonols, flavones, flavanones, isoflavones, flavan-3-ols and anthocyanins) and gut microbiota. We aim to provide a holistic overview of the nature and identity of flavonoids on diet and highlight how flavonoids chemical structure, metabolism and impact on humans and their microbiomes are interconnected. Emphasis is placed on how flavonoids and their biotransformation products affect gut microbiota population, influence gut homoeostasis and induce measurable physiological changes and biological benefits.
Constant Companion: How Frequent Phone Use and Interpersonal Communication Are Related to Users’ Emotional Appraisal

Emotional appraisal is a core aspect of user experience. This study examines whether frequency of mobile phone use can have an impact on emotional aspects of mobile phone user experience. It also comments on the role of interpersonal communication for emotional evaluation. The results of an online survey in Germany (N = 836) reveal that frequencies are related to positive and negative emotions differently. Frequent phone users experience more positive emotions than others, but the frequent use of a mobile phone does not seem to reduce negative emotions. Surprisingly, this effect does not depend on the extent of interpersonal communication. Positive emotions seem to be stronger connected to a positive user experience, whereas negative emotions probably occur due to a bad usability. This can be interpreted as an evidence for Herzberg’s two-factor theory applied to user experience.
Reminders of COVID‐19 social distancing can intensify physical pain

Social distance regulations have been widely implemented to control the global COVID‐19 pandemic. Individuals have thus been experiencing social pain through social distance regulations. Prior research has shown that social and physical pains share a common neural alarm system. Hence, COVID‐19 social distancing should enhance sensitivity to physical pain. Two laboratory studies were conducted to test the spillover effect of COVID‐19 social distancing on physical pain. The findings supported our hypothesis by showing that participants who were reminded of COVID‐19 social distancing reported a higher level of pain perception in response to immersion in hot water (Experiment 1, N = 102) and expressed a lower pain threshold measured by a pressure algometer than did those of controls (Experiment 2, N = 140). This may be the first experimental evidence demonstrating that people primed with COVID‐19 social distancing have increased sensitivity to physical pain. Our findings suggest that people might be more likely to experience physical pain under the impact of COVID‐19 social distancing. The association between a heightened sense of social disconnection in a global pandemic and increased sensitivity to physical pain should receive more attention.