julilili42/papers huggingface dataset:
A nanobody-based toolset to monitor and modify the mitochondrial GTPase Miro1
2021-12-10

Abstract The mitochondrial outer membrane (MOM)-anchored GTPase Miro1, is a central player in mitochondrial transport and homeostasis. The dysregulation of Miro1 in amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) suggests that Miro1 may be a potential biomarker or drug target in neuronal disorders. However, the molecular functionality of Miro1 under (patho-) physiological conditions is poorly known. For a more comprehensive understanding of the molecular functions of Miro1, we have developed Miro1-specific nanobodies (Nbs) as novel research tools. We identified seven Nbs that bind either the N- or C-terminal GTPase domain of Miro1 and demonstrate their application as research tools for proteomic and imaging approaches. To visualize the dynamics of Miro1 in real time, we selected intracellularly functional Nbs, which we reformatted into chromobodies (Cbs) for time- lapse imaging of Miro1. By genetic fusion to an Fbox domain, these Nbs were further converted into Miro1-specific degrons and applied for targeted degradation of Miro1 in live cells. In summary, this study presents a collection of novel Nbs that serve as a toolkit for advanced biochemical and intracellular studies and modulations of Miro1, thereby contributing to the understanding of the functional role of Miro1 in disease-derived model systems.
Integration of visual motion and pursuit signals in areas V3A and V6+ across cortical depth using 9.4T fMRI
2021-12-10

ABSTRACT Neural mechanisms underlying a stable perception of the world during pursuit eye movements are not fully understood. Both, perceptual stability as well as perception of real (i.e. objective) motion are the product of integration between motion signals on the retina and efference copies of eye movements. Human areas V3A and V6 have previously been shown to have strong objective (‘real’) motion responses. Here we used high-resolution laminar fMRI at ultra-high magnetic field (9.4T) in human subjects to examine motion integration across cortical depths in these areas. We found an increased preference for objective motion in areas V3A and V6+ i.e. V6 and possibly V6A towards the upper layers. When laminar responses were detrended to remove the upper-layer bias present in all responses, we found a unique, condition-specific laminar profile in V6+, showing reduced mid-layer responses for retinal motion only. The results provide evidence for differential, motion-type dependent laminar processing in area V6+. Mechanistically, the mid-layer dip suggests a special contribution of retinal motion to integration, either in the form of a subtractive (inhibitory) mid-layer input, or in the form of feedback into extragranular or infragranular layers. The results show that differential laminar signals can be measured in high-level motion areas in the human occipitoparietal cortex, opening the prospect of new mechanistic insights using non-invasive brain imaging. Significance Statement Visual stability and our ability to differentiate between self-induced and real motion are central to our visual sense. Both require the integration of two signals – retinal motion and copies of muscle commands used for eye movements (efference copies). A reasonable assumption is that either the efference copy or the result of integration will be conveyed to high-level visual regions along with visual retinal input, possibly differentially across cortical depth as the input sources differ. Our ultra-high field recordings present the first laminar evidence of differential signal processing of retinal and objective motion signals in area V6+, and present a first window into a mechanistic understanding of visual high-level motion processing.
Lying Without Saying Something False? A Cross-Cultural Investigation of the Folk Concept of Lying in Russian and English Speakers
2021-12-11

Abstract The present study examines cross-cultural differences in people’s concept of lying with regard to the question of whether lying requires an agent to say something they believe to be false. While prominent philosophical views maintain that lying entails that a person explicitly expresses a believed-false claim, recent research suggests that people’s concept of lying might also include certain kinds of deception that are communicated more indirectly. An important drawback of previous empirical work on this topic is that only few studies have investigated people’s concept of lying in non-Western samples. In the present study, we compare people’s intuitions about lying with indirect deceptions (i.e., presuppositions, conversational implicatures, and non-verbal actions) in a sample of N = 255 participants from Russia and N = 300 participants from the United Kingdom. Our findings show a strong degree of similarity between lie ratings of participants from Russia and the United Kingdom, with both samples holding it possible for agents to lie with deceptive statements and actions that do not involve the agent saying something they believe to be false.
Simultaneous Determination of Droplet Size, pH Value and Concentration to Evaluate the Aging Behavior of Metalworking Fluids
2021-12-11

Metalworking fluids (MWFs) are widely used to cool and lubricate metal workpieces during processing to reduce heat and friction. Extending a MWF’s service life is of importance from both economical and ecological points of view. Knowledge about the effects of processing conditions on the aging behavior and reliable analytical procedures are required to properly characterize the aging phenomena. While so far no quantitative estimations of ageing effects on MWFs have been described in the literature other than univariate ones based on single parameter measurements, in the present study we present a simple spectroscopy-based set-up for the simultaneous monitoring of three quality parameters of MWF and a mathematical model relating them to the most influential process factors relevant during use. For this purpose, the effects of MWF concentration, pH and nitrite concentration on the droplet size during aging were investigated by means of a response surface modelling approach. Systematically varied model MWF fluids were characterized using simultaneous measurements of absorption coefficients μa and effective scattering coefficients μ’s. Droplet size was determined via dynamic light scattering (DLS) measurements. Droplet size showed non-linear dependence on MWF concentration and pH, but the nitrite concentration had no significant effect. pH and MWF concentration showed a strong synergistic effect, which indicates that MWF aging is a rather complex process. The observed effects were similar for the DLS and the μ’s values, which shows the comparability of the methodologies. The correlations of the methods were R2c = 0.928 and R2P = 0.927, as calculated by a partial least squares regression (PLS-R) model. Furthermore, using μa, it was possible to generate a predictive PLS-R model for MWF concentration (R2c = 0.890, R2P = 0.924). Simultaneous determination of the pH based on the μ’s is possible with good accuracy (R2c = 0.803, R2P = 0.732). With prior knowledge of the MWF concentration using the μa-PLS-R model, the predictive capability of the μ’s-PLS-R model for pH was refined (10 wt%: R2c = 0.998, R2p = 0.997). This highlights the relevance of the combined measurement of μa and μ’s. Recognizing the synergistic nature of the effects of MWF concentration and pH on the droplet size is an important prerequisite for extending the service life of an MWF in the metalworking industry. The presented method can be applied as an in-process analytical tool that allows one to compensate for ageing effects during use of the MWF by taking appropriate corrective measures, such as pH correction or adjustment of concentration.
Aspektualität in deutschen Partikel- und Präfixverben
2021-12-11

Prefix and particle verbs are part of a systematic way of expressing aspectual structures in German. This article proposes an aspectual analysis of German particle and prefixed verbs, regarding especially their polysemic characteristics, and will give a contrastive comparison with the Italian language. This can be useful given that Italian does not have developed a system of prefixes and particles as German does. Therefore, the Italian translations of German prefixed and particle verbs turns out to use different kinds of expressions, often of a periphrastic nature. This is seen here as an indication in favour of the strongly polysemic verbs in German. The aspectual comparison of both languages will be done using an onomasiological model of aspectuality, which allows the analysis of different kinds of expressions without using specific formal categories.&#x0D; The first part of this article gives a short introduction and definition of the German verbs. Part two concerns the question of what aspectuality in German is, followed by part three, a quick overview of actual research in the field. Part four explains how a contrastive perspective may be helpful to discover and illuminate the polysemic German prefixed and particle verbs. Part five presents the empirical data used for the purpose of this work. Part six, then, contains the aspectual analysis of the German verbs in their given context. Every German example will be described and compared to its Italian translation. The article will close with a quick summary of the results, focussing especially on the usefulness of a contrastive approach.
Ovarian tissue cryopreservation in a patient with breast cancer during pregnancy: a case report
2021-12-12

Abstract Background Fertility preservation using ovarian tissue cryopreservation (OTC) in patients with certain diseases, especially those needing chemo- or radiotherapy, is becoming routine in various Western countries. Our hospital is the first and until now the only centre in China to use this method. The question of whether treatment of breast cancer during pregnancy (PrBC) should be similar to non-pregnant young patients with breast cancer is controversial. To our knowledge, this is the first report worldwide to use OTC as fertility preservation for PrBC. Case presentation During the 29th week of pregnancy, a 24-year-old woman underwent needle aspiration cytology of a left breast tumour. Ultrasound and cytology revealed BI-RADS 4a grade. Oncologists recommended termination of the pregnancy. Caesarean section was performed at week 32, and ovarian tissue samples were collected for OTC to preserve fertility and ovarian endocrine function. Twenty-three ovarian cortex slices were cryopreserved. It is estimated that 13,000 follicles were cryopreserved. Breast nodules and sentinel lymph node biopsy suggested invasive micropapillary carcinoma. Neoadjuvant chemotherapy was started within 1 week after diagnosis. After six courses of neoadjuvant chemotherapy, targeted drug therapy and goserelin acetate, left mastectomy and left axillary lymph node dissection were performed. In total, 23 doses of radiotherapy, eight trastuzumab targeted therapy treatments, and 17 pertuzumab + trastuzumab double targeted therapy treatments were performed after breast cancer surgery. Until now, more than 2 years after delivery, the ovarian function still is good, and no signs of a negative impact of OTC have been observed. Goserelin acetate injections, administered every 28 days, are planned to last for the next 5 years. In addition, endocrine therapy with anastrozole was started after breast cancer surgery and also is scheduled for 5 years. Conclusion OTC for fertility preservation in patients with PrBC does not delay breast surgery, radiotherapy or chemotherapy, which is essential for effective treatment of breast cancer. We assess this method as a promising fertility preservation method which was used here for the first time worldwide in a patient who developed breast cancer during pregnancy.
Efficient ancestry and mutation simulation with msprime 1.0
2021-12-13

Abstract Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.
A discriminative account of the learning, representation and processing of inflection systems
2021-12-13

What kind of knowledge accounts for linguistic productivity? How is it acquired? For years, debate on these questions has focused on a seemingly obscure domain: inflectional morphology. On one side, theorists inspired by Rumelhart & McClelland's classic error-driven learning model have sought to show how all morphological forms are the products of a single memory-based process, whereas the opposing theories have claimed that irregular forms are processed by qualitatively different mechanisms to rule-governed regulars. This review argues that while the main ideas put forward by Rumelhart & McClelland – that inflectional patterns are learned, and rule-like behaviour emerges from the distribution of forms – appear to be correct, the theory embodied in their model (and those following it) is incompatible with the discriminative nature of learning itself. An examination of the constraints error-driven learning mechanisms impose on theories of morphological processing – along with language learning and human communication itself – is presented.
A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials
2021-12-13

Objective The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies. Methods In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set). Results We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R 2 = 0.423; C-index = 0.749) included residual tumor volume, age, O 6 -methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models. Conclusions A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.
NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression
2021-12-13

This study investigates the diagnostic and prognostic potential of different forms of tau in biofluids from patients with Creutzfeldt-Jakob disease (CJD). Extracellular tau, which is molecularly heterogeneous, was measured using ultra-sensitive custom-made Simoa assays for N-terminal (NT1), mid-region, and full-length tau. We assessed cross-sectional CSF and plasma from healthy controls, patients with Alzheimer’s disease (AD) and CJD patients. Then, we evaluated the correlation of the best-performing tau assay (NT1-tau) with clinical severity and functional decline (using the MRC Prion Disease Rating Scale) in a longitudinal CJD cohort (n = 145). In a cross-sectional study, tau measured in CSF with the NT1 and mid-region Simoa assays, separated CJD (n = 15) from AD (n = 18) and controls (n = 21) with a diagnostic accuracy (AUCs: 0.98–1.00) comparable to or better than neurofilament light chain (NfL; AUCs: 0.96–0.99). In plasma, NT1-measured tau was elevated in CJD (n = 5) versus AD (n = 15) and controls (n = 15). Moreover, in CJD plasma (n = 145) NT1-tau levels correlated with stage and rate of disease progression, and the effect on clinical progression was modified by the PRNP codon 129. Our findings suggest that plasma NT1-tau shows promise as a minimally invasive diagnostic and prognostic biomarker of CJD, and should be further investigated for its potential to monitor disease progression and response to therapies.
Speech Development in Cleft Palate with and without Robin Sequence
2021-12-13

Background: Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years. Methods: All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes. Results: Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p &lt; 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate ( p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate–only group. Statistical analysis revealed no significant effect of group ( Z = −1.47; p = 0.14). Conclusions: No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
Can Any Drug Be Repurposed for Cancer Treatment? A Systematic Assessment of the Scientific Literature
2021-12-13

Drug repurposing is a complementary pathway for introducing new drugs against cancer. Broad systematic assessments of ongoing repurposing efforts in oncology are lacking, but may be helpful to critically appraise current and future efforts. Hence, we conducted a systematic PubMed search encompassing 100 frequently prescribed and 100 randomly selected drugs, and assessed the published preclinical anti-cancer effects. Furthermore, we evaluated all the identified original articles for methodological quality. We found reports indicating anti-cancer effects for 138/200 drugs, especially among frequently prescribed drugs (81/100). Most were reports suggesting single-agent activity of the drugs (61%). Basic information, such as the cell line used or control treatments utilized, were reported consistently, while more detailed information (e.g., excluded data) was mostly missing. The majority (56%) of in vivo studies reported randomizing animals, while only few articles stated that the experiments were conducted in a blinded fashion. In conclusion, we found promising reports of anti-cancer effects for the majority of the assessed drugs, but speculate that many of them are false-positive findings. Reward systems should be adjusted to encourage the widespread usage of high reporting quality and bias-reducing methodologies, aiming to decrease the rate of false-positive results, and thereby increasing the trust in the findings.
Coordinating social action: A primer for the cross-species investigation of communicative repair
2021-12-13

Human joint action is inherently cooperative, manifested in the collaborative efforts of participants to minimize communicative trouble through interactive repair. Although interactive repair requires sophisticated cognitive abilities, it can be dissected into basic building blocks shared with nonhuman animal species. A review of the primate literature shows that interactionally contingent signal sequences are at least common among species of nonhuman great apes, suggesting a gradual evolution of repair. To pioneer a cross-species assessment of repair this paper aims at (i) identifying necessary precursors of human interactive repair; (ii) proposing a coding framework for its comparative study in humans and nonhuman species; and (iii) using this framework to analyse examples of interactions of humans (adults/children) and nonhuman great apes. We hope this paper will serve as a primer for cross-species comparisons on dealing with communicative breakdowns.
Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry
2021-12-13

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy. Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded. Outcomes: The collected data will be used for establishing standardized reference values (“benchmarks”) for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications. Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).