julilili42/papers huggingface dataset:
Questionnaire choice affects the prevalence of recommended physical activity: an online survey comparing four measuring instruments within the same sample
2021-01-07

Abstract Background Since prevalence estimates of recommended physical activity (PA) considerably vary between different surveys, prevalence might be crucially affected by the choice of measuring instrument. The aim of the present study is to compare the results of four PA questionnaires regarding the current moderate- and vigorous-intensity aerobic PA (MVPA) recommendations of the World Health Organization. Methods Within an online survey, participants answered the German Health Interview and Examination Survey for Adults ( DEGS ), the European Health Interview Survey PA Questionnaire ( EHIS ), the Eurobarometer ( EURO ), and a single-item measure ( SIM ). Weekly volume of MVPA was compared via a Friedman test and the prevalence of participants achieving the WHO’s MVPA recommendation via Cochran’s Q. Agreement between all questionnaire pairs was evaluated via Kappa statistics. Results One hundred seventy-six participants were included in the analyses (70.5% female, mean age: 33.1 years (SD=12.2)). Between the four questionnaires, the weekly volume of MVPA statistically significant differed ( SIM : MED=90.0 (MIN=0.0, MAX=210.0), DEGS : MED=120.0 (MIN=0.0, MAX=420.0), EHIS : MED=240.0 (MIN=0.0, MAX=1395.0), EURO : MED=510.0 (MIN=0.0, MAX=2430.0), p &lt;.001, all pairwise comparisons p &lt;.01), as well as the prevalence of participants achieving the MVPA recommendations ( SIM 31.3% (95% CI 24.5–38.7) , DEGS 43.2% (95% CI 35.8–50.8), EHIS 67.0% (95% CI 59.6–73.9), EURO 87.5% (95% CI 81.7–92.0), p &lt;.001), except between SIM and DEGS ( p =.067). Agreement was weak between all questionnaire pairs (all κ&lt; 0.60). Conclusions Questionnaire choice crucially affects the resulting MVPA data and hence the prevalence of achieving recommended PA levels within the same sample. Therefore, for PA surveillance, standardised survey and analysis methods and efforts to harmonise monitoring systems are needed, since whether recommended levels of PA are achieved should not be determined by the choice of one measuring instrument or another.
Determining the pathogenicity of variants of uncertain significance and identification of a founder variant in the epilepsy-associated gene,SZT2
2021-01-07

Abstract Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTOR signaling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions. We report a cohort of twelve individuals with biallelic SZT2 variants and phenotypes consistent with SZT2 -related neurodevelopmental disorder. The majority of this cohort contained one or more SZT2 variants of uncertain significance (VUS). We developed a novel individualized platform to functionally characterize SZT2 VUSs. We identified a recurrent in-frame deletion (SZT2 p.Val1984del) which was determined to be a loss-of-function variant and therefore likely pathogenic. Haplotype analysis determined this single in-frame deletion is a founder variant in those of Ashkenazi Jewish ancestry. Overall, we present a FACS-based rapid assay to distinguish pathogenic variants from VUSs in SZT2 , using an approach that is widely applicable to other mTORopathies including the most common causes of the focal genetic epilepsies, DEPDC5, TSC1/2, MTOR and NPRL2 /3.
Cover Feature: Energetics of Formation of Cyclacenes from 2,3‐Didehydroacenes and Implications for Astrochemistry (Chem. Eur. J. 14/2021)
2021-01-07

Rolling up: Larger acenes are potential carriers of diffuse interstellar bands, and should undergo dehydrogenation reactions upon absorption of interstellar UV photons. This could result in 2,3-didehydroacenes that have a reactive aryne functionality at one of the short ends of the long molecule. The intramolecular Diels-Alder reaction to dihydroethenocyclacenes with the other end of the acene and the subsequent cycloreversion of acetylene were studied computationally and were shown to have energy requirements that are compatible with cyclacene formation under the extreme conditions of interstellar space. More information can be found in the Full Paper by H. F. Bettinger et al. on page 4605.
Linguistic and cultural divisions in pre-Hispanic Northern Peru
2021-01-08

Interdisciplinary research at the interface of linguistics and archaeology is often concerned with relationships between archaeological cultures and language families, their subgroups, or their proto-languages. This often makes the problematic assumption of a one-to-one correspondence between groupings from the two disciplines. Here, I show how evidence from Northern Peru, a region which once hosted a myriad of well-differentiated local languages and an equally multifaceted sequence of more or less localized pre-Hispanic cultures, can contribute complementary perspectives to existing models. After providing some summary background information, I discuss two regions of Northern Peru –the North Coast and the cloud forests of Chachapoyas– which both exhibit linguistic divisions that correspond to differences in the archaeological record within what has (traditionally) been taken to constitute overarching archaeological cultures; differences in language and cultural expression may both be interpretable as indexes of different pre-Hispanic social, ethnic, or political identities and allegiances. These cases underscore that one-to-one mappings between languages and archaeological cultures (or their expansions) may in some cases be inadequate.
Chromatin phosphoproteomics unravels a function for AT-hook motif nuclear localized protein AHL13 in PAMP-triggered immunity
2021-01-08

Significance Mitogen-activated protein kinases (MAPKs) function in all eukaryotes in signaling extracellular stimuli to intracellular responses and ultimately link them to chromatin events by targeting transcription factors and chromatin remodeling complexes. In plants, MAPKs play crucial roles in immunity, development, and stress responses, but so far no attempts have been made to identify phosphorylation of chromatin-associated proteins. By using a phosphoproteomic approach on MAPK mutants, we identified a number of chromatin-associated MAPK substrates and characterize an AT-hook motif containing nuclear localized (AHL) DNA-binding protein 13 in plant immunity and demonstrate that phosphorylation regulates AHL13 protein stability and, in turn, its function in response to pathogens.
Dating of the Lower Pleistocene Vertebrate Site of Tsiotra Vryssi (Mygdonia Basin, Greece): Biochronology, Magnetostratigraphy, and Cosmogenic Radionuclides
2021-01-08

Background and scope: The late Villafranchian large mammal age (~2.0–1.2 Ma) of the Early Pleistocene is a crucial interval of time for mammal/hominin migrations and faunal turnovers in western Eurasia. However, an accurate chronological framework for the Balkans and adjacent territories is still missing, preventing pan-European biogeographic correlations and schemes. In this article, we report the first detailed chronological scheme for the late Villafranchian of southeastern Europe through a comprehensive and multidisciplinary dating approach (biochronology, magnetostratigraphy, and cosmogenic radionuclides) of the recently discovered Lower Pleistocene vertebrate site Tsiotra Vryssi (TSR) in the Mygdonia Basin, Greece. Results: The minimum burial ages (1.88 ± 0.16 Ma, 2.10 ± 0.18 Ma, and 1.98 ± 0.18 Ma) provided by the method of cosmogenic radionuclides indicate that the normal magnetic polarity identified below the fossiliferous layer correlates to the Olduvai subchron (1.95–1.78 Ma; C2n). Therefore, an age younger than 1.78 Ma is indicated for the fossiliferous layer, which was deposited during reverse polarity chron C1r. These results are in agreement with the biochronological data, which further point to an upper age limit at ~1.5 Ma. Overall, an age between 1.78 and ~1.5 Ma (i.e., within the first part of the late Villafranchian) is proposed for the TSR fauna. Conclusions: Our results not only provide age constraints for the local mammal faunal succession, thus allowing for a better understanding of faunal changes within the same sedimentary basin, but also contribute to improving correlations on a broader scale, leading to more accurate biogeographic, palaeoecological, and taphonomic interpretations.
Quality of oxytocin and misoprostol in health facilities of Rwanda
2021-01-08

Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2–8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2–121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5–48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities.
Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC
2021-01-08

Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status.
Heart rate variability predicts decline in sensorimotor rhythm control
2021-01-08

Abstract Voluntary control of sensorimotor rhythms (SMR, 8-12 Hz) can be used for brain-computer interface (BCI)-based operation of an assistive hand exoskeleton, e.g., in finger paralysis after stroke. To gain SMR control, stroke survivors are usually instructed to engage in motor imagery (MI) or to attempt moving the paralyzed fingers resulting in task- or event-related desynchronization (ERD) of SMR (SMR-ERD). However, as these tasks are cognitively demanding, especially for stroke survivors suffering from cognitive impairments, BCI control performance can deteriorate considerably over time. It would thus be important to identify biomarkers that predict decline in BCI control performance within an ongoing session in order to optimize the man-machine interaction scheme. Here we determine the link between BCI control performance over time and heart rate variability (HRV). Specifically, we investigated whether HRV can be used as a biomarker to predict decline during voluntary control of SMR-ERD across 17 healthy participants using Granger causality. SMR-ERD was visually displayed on a screen. Participants were instructed to engage in MI-based SMR-ERD control over two consecutive runs of 8.5 minutes each. During the second run, task difficulty was gradually increased. While control performance ( p = .18) and HRV ( p = .16) remained unchanged across participants during the first run, during the second run, both measures declined over time at high correlation (performance: -0.61%/10s, p = 0; HRV: -0.007ms/10s, p &lt; .001). We found that HRV Granger-caused BCI control performance ( p &lt; .001) exhibited predictive characteristics of HRV on an individual participant level. These results suggest that HRV can predict decline in BCI performance paving the way for adaptive BCI control paradigms, e.g., to individualize and optimize assistive BCI systems in stroke.
Integration and segregation across large-scale intrinsic brain networks as a marker of sustained attention and task-unrelated thought
2021-01-09

Sustained attention is a fundamental cognitive process that can be decoupled from distinct external events, and instead emerges from ongoing intrinsic large-scale network interdependencies fluctuating over seconds to minutes. Lapses of sustained attention are commonly associated with the subjective experience of mind wandering and task-unrelated thoughts. Little is known about how fluctuations in information processing underpin sustained attention, nor how mind wandering undermines this information processing. To overcome this, we used fMRI to investigate brain activity during subjects' performance (n=29) of a cognitive task that was optimized to detect and isolate continuous fluctuations in both sustained attention (via motor responses) and task-unrelated thought (via subjective reports). We then investigated sustained attention with respect to global attributes of communication throughout the functional architecture, i.e., by the segregation and integration of information processing across large scale-networks. Further, we determined how task-unrelated thoughts related to these global information processing markers of sustained attention. The results show that optimal states of sustained attention favor both enhanced segregation and reduced integration of information processing in several task-related large-scale cortical systems with concurrent reduced segregation and enhanced integration in the auditory and sensorimotor systems. Higher degree of mind wandering was associated with losses of the favored segregation and integration of specific subsystems in our sustained attention model. Taken together, we demonstrate that intrinsic ongoing neural fluctuations are characterized by two converging communication modes throughout the global functional architecture, which give rise to optimal and suboptimal attention states. We discuss how these results might potentially serve as neural markers for clinically abnormal attention. SIGNIFICANCE STATEMENT: Most of our brain activity unfolds in an intrinsic manner, i.e., is unrelated to immediate external stimuli or tasks. Here we use a gradual continuous performance task to map this intrinsic brain activity to both fluctuations of sustained attention and mind wandering. We show that optimal sustained attention is associated with concurrent segregation and integration of information processing within many large-scale brain networks, while task-unrelated thought is related to sub-optimal information processing in specific subsystems of this sustained attention network model. These findings provide a novel information processing framework for investigating the neural basis of sustained attention, by mapping attentional fluctuations to genuinely global features of intra-brain communication.
International primate neuroscience research regulation, public engagement and transparency opportunities
2021-01-09

Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care ("culture of care") and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research.
Corrigendum to “Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany”
2021-01-09

In Fig. 2c and f of our publication Schneeweiss et al. [1] we mistakenly placed wrong Kaplan Meier Plots. In the attached figure this was corrected. All other estimates concerning the survival including the regression models are correct. We apologize for the mistake.1.Schneeweiss A, Ettl J, Luftner D et al. Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer - Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany. Breast 2020; 54: 88–95. Fig. 2. Progression-free survival (PFS) and overall survival (OS) for the total group analyzed. CDK4/6i, CDK4/6 inhibitors; ET, endocrine therapy; OS, overall survival; PFS, progression-free survival.Tabled 12a (PFS first-line setting)2b (OS first-line setting)2c (PFS second-line setting)2d (OS second-line setting)2e (PFS third-line setting)2f (OS third-line setting) Open table in a new tab Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in GermanyThe BreastVol. 54PreviewTreatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor–positive, HER2-negative (HR + HER2–) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported. Full-Text PDF Open Access
Explainable Online Validation of Machine Learning Models for Practical Applications
2021-01-10

We present a reformulation of the regression and classification, which aims to validate the result of a machine learning algorithm. Our reformulation simplifies the original problem and validates the result of the machine learning algorithm using the training data. Since the validation of machine learning algorithms must always be explainable, we perform our experiments with the kNN algorithm as well as with an algorithm based on conditional probabilities, which is proposed in this work. For the evaluation of our approach, three publicly available data sets were used and three classification and two regression problems were evaluated. The presented algorithm based on conditional probabilities is also online capable and requires only a fraction of memory compared to the kNN algorithm.
Fully Convolutional Neural Networks for Raw Eye Tracking Data Segmentation, Generation, and Reconstruction
2021-01-10

In this paper, we use fully convolutional neural networks for the semantic segmentation of eye tracking data. We also use these networks for reconstruction, and in conjunction with a variational auto-encoder to generate eye movement data. The first improvement of our approach is that no input window is necessary, due to the use of fully convolutional networks and therefore any input size can be processed directly. The second improvement is that the used and generated data is raw eye tracking data (position X, Y and time) without preprocessing. This is achieved by pre-initializing the filters in the first layer and by building the input tensor along the z axis. We evaluated our approach on three publicly available datasets and compare the results to the state of the art.