julilili42/papers huggingface dataset:
Dose-Dependent Tissue-Level Characterization of a Medical Atmospheric Pressure Argon Plasma Jet
2019-05-09

Nonthermal treatment with cold atmospheric plasma (CAP) is a promising option for local treatment of chronic-inflammatory and precancerous lesions as well as various mucosal cancer diseases, besides its primary indication for wound healing and antiseptics. Atmospheric pressure plasma jets (APPJs) are versatile plasma sources, some of which are well-characterized and medically approved. The characterization of APPJs, however, is often based on the treatment of simple solutions or even studies on the plasma effluent itself. To better assess the in vivo effects of CAP treatment, this study aims to recapitulate and study the physicochemical tissue-level effects of APPJ treatment on human primary mucosal tissue and tissue models. High resolution on-tissue infrared (IR) thermography and a first-time-performed spatially resolved optical emission spectroscopy (OES) of the APPJ emissions did not identify potentially tissue-harming effects. In this study, electron-spin-resonance (ESR) spectroscopy on human tissue samples, treated with different CAP doses, enabled the measurement and the distribution of CAP-derived radicals in the tissues. The results correlate plasma dosage and the generation of radical species with cell viability and cell proliferation of primary human fibroblasts while demonstrating apoptosis-independent antiproliferative cell effects. Moreover, a dose-dependent increase of cells in the G1 phase of the cell cycle was observed, stressing the likely important role of cell cycle regulation for antiproliferative CAP mechanisms. This study introduces suitable methods for CAP monitoring on tissues and contributes to a better understanding of tissue-derived plasma effects of APPJs.
Assessment of complex projectiles in the early Late Pleistocene at Aduma, Ethiopia
2019-05-09

Complex projectiles-propulsion via mechanical aid-are considered an important technological innovation, with possible relevance for the successful Out-of-Africa dispersal of our species. Conclusive evidence for the beginning of this technology, however, is lacking from the early Late Pleistocene (ca. 130 to 70 thousand years ago; ka). Given the extremely limited applicability of relatively robust methods for validating stone-tipped projectile use, such as through fracture propagation velocity, converging lines of circumstantial evidence remain the best way to examine early complex projectiles. We assess here suggestions for an early Late Pleistocene origin of complex projectiles in Africa. Results from both previous and present independent approaches suggest a trajectory in which complex projectiles were likely adopted during the early Late Pleistocene in eastern Africa. At Aduma (Middle Awash, Ethiopia), morphometric, hafting, and impact damage patterns in several lithic point assemblages suggest a shift from simple spear technologies (thrusting and/or hand-cast) to complex projectiles. Broadly dated to 80-100 ka, lithic points from later phases of the Aduma succession represent a particularly strong candidate for projectile armatures most comparable to ethnographically known spearthrower darts, lending support for previous suggestions and warranting further investigations.
Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches
2019-05-09

Abstract Background Phosphorylated neurofilament heavy (pNfH), a neuronal cytoskeleton protein, might provide a promising blood biomarker of neuronal damage in neurodegenerative diseases (NDDs). The best analytical approaches to measure pNfH levels and whether serum levels correlate with cerebrospinal fluid (CSF) levels in NDDs remain to be determined. Methods We here compared analytical sensitivity and reliability of three novel analytical approaches (homebrew Simoa, commercial Simoa and ELISA) for quantifying pNfH in both CSF and serum in samples of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and control subjects. Results While all three assays showed highly correlated CSF measurements, Simoa assays also yielded high between-assay correlations for serum measurements (ρ = 0.95). Serum levels also correlated strongly with CSF levels for Simoa-based measurements (both ρ = 0.62). All three assays allowed distinguishing ALS from controls by increased CSF pNfH levels, and Simoa assays also by increased serum pNfH levels. pNfH levels were also increased in FTD. Conclusions pNfH concentrations in CSF and, if measured by Simoa assays, in blood might provide a sensitive and reliable biomarker of neuronal damage, with good between-assay correlations. Serum pNfH levels measured by Simoa assays closely reflect CSF levels, rendering serum pNfH an easily accessible blood biomarker of neuronal damage in NDDs.
Gata3 is required for the functional maturation of inner hair cells and their innervation in the mouse cochlea
2019-05-09

Key points The physiological maturation of auditory hair cells and their innervation requires precise temporal and spatial control of cell differentiation. The transcription factor gata3 is essential for the earliest stages of auditory system development and for survival and synaptogenesis in auditory sensory afferent neurons. We show that during postnatal development in the mouse inner ear gata3 is required for the biophysical maturation, growth and innervation of inner hair cells; in contrast, it is required only for the survival of outer hair cells. Loss of gata3 in inner hair cells causes progressive hearing loss and accounts for at least some of the deafness associated with the human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome. The results show that gata3 is critical for later stages of mammalian auditory system development where it plays distinct, complementary roles in the coordinated maturation of sensory hair cells and their innervation. Abstract The zinc finger transcription factor gata3 regulates inner ear development from the formation of the embryonic otic placode. Throughout development, gata3 is expressed dynamically in all the major cochlear cell types. Its role in afferent formation is well established but its possible involvement in hair cell maturation remains unknown. Here, we find that in heterozygous gata3 null mice ( gata3 +/− ) outer hair cells (OHCs) differentiate normally but their numbers are significantly lower. In contrast, inner hair cells (IHCs) survive normally but they fail to acquire adult basolateral membrane currents, retain pre‐hearing current and efferent innervation profiles and have fewer ribbon synapses. Targeted deletion of gata3 driven by otoferlin‐cre recombinase ( gata3 fl/fl otof‐cre +/− ) in IHCs does not affect OHCs or the number of IHC afferent synapses but it leads to a failure in IHC maturation comparable to that observed in gata3 +/− mice. Auditory brainstem responses in gata3 fl/fl otof‐cre +/− mice reveal progressive hearing loss that becomes profound by 6–7 months, whilst distortion product otoacoustic emissions are no different to control animals up to this age. Our results, alongside existing data, indicate that gata3 has specific, complementary functions in different cell types during inner ear development and that its continued expression in the sensory epithelium orchestrates critical aspects of physiological development and neural connectivity. Furthermore, our work indicates that hearing loss in human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome arises from functional deficits in IHCs as well as loss of function from OHCs and both afferent and efferent neurons.
Heart rate variability categories of fluctuation amplitude and complexity: diagnostic markers of fetal development and its disturbances
2019-05-09

Abstract Objective : In fetal diagnosis the myriad and diversity of heart rate variability (HRV) indices prevents a comparable routine evaluation of disturbances in fetal development and well-being. The work aims at the extraction of a small set of HRV key indices that could help to establish a universal, overarching tool to screen for any disturbance. Approach : HRV indices were organized in categories of short-term (prefix s) and long-term (prefix l) amplitude fluctuations (AMP), complexity (COMP), and patterns (PATTERN) and common representatives for each category were extracted. This procedure was done with respect to the diagnostic value in the evaluation of the maturation age throughout the second and complete third trimester of pregnancy as well as to potential differences associated with maternal life-style factors (physical exercise, smoking), nutrient intervention (docosahexaenoic acid (DHA) supplementation), and complications of pregnancy (gestational diabetes mellitus (GDM), intra-uterine growth restriction (IUGR)). Main results : We found a comprehensive minimal set that includes [lAMP: short term variation (STV), initially introduced in cardiotocography, sAMP: heart rate increase across one interbeat interval of phase rectified averaged signal - acceleration capacity (ACst1), lCOMP: scale 4 multi-scale entropy (MSE4), PATTERN: skewness] for the maturation age prediction, and partly overlapping [lAMP: STV, sAMP: ACst1, sCOMP: Lempel Ziv complexity (LZC)] for the discrimination of the deviations. Significance : The minimal set of category-based HRV representatives allows for a screening of fetal development and well-being. These results are an important step towards a universal and comparable diagnostic tool for the early identification of developmental disturbances. Novelty &amp; Significance Fetal development and its disturbances have been reported to be associated with a multiplicity of HRV indices. Furthermore, these HRV indices change with maturation. We propose the abstraction of HRV categories defined by short- and long-term fluctuation amplitude, complexity, and pattern indices that cover all relevant aspects of maturational age, behavioral influences and a series of pathological disturbances. The study data are provided by multiple centers. Our approach is an important step towards the goal of a standardized diagnostic tool for early identification of fetal developmental disturbances with respect to the reduction of serious complications in the later life.
Multipole moments and universal relations for scalarized neutron stars
2019-05-09

In recent years there has been a surge of interest in what has come to be\\nknown as the `universal relations' between various global properties of neutron\\nstars. These universal relations are equation of state independent relations\\nbetween quantities such as the moment of inertia , the tidal deformability\\nor Love number , and the quadrupole (I-Love-Q relations), or the\\nrelativistic multipole moments (3-hair relations). While I-Love-Q relations\\nhave been studied extensively in both general relativity and various\\nalternatives, 3-hair relations have been studied only in general relativity.\\nRecent progress on the definition of the multipole moments of a compact object\\nin the case of scalar-tensor theories allows for the study of 3-hair relations\\nin modified theories of gravity. Specifically, the aim of this work is to study\\nthem for scalarized stars in scalar-tensor theories with a massless scalar\\nfield that admit spontaneous scalarization. We find that the 3-hair relations\\nbetween the mass and angular momentum moments that hold in general relativity\\nhold for scalarized stars as well. The scalar moments also exhibit a universal\\nbehaviour, which is equation of state independent within one specific theory,\\nbut differs between different theories. Combining astrophysical observations\\none can in principle measure the different properties of scalarized neutron\\nstar and tell different theories apart.\\n
Distribution of the cytochrome P450 CYP2C8*2 allele in Brazzaville, Republic of Congo
2019-05-09

This study gives the first description of CYP2C8*2 allele distribution in the Republic of Congo and highlights the potential risk of amodiaquine-related adverse events. Information from this study will be beneficial during pharmacovigilance investigations.
web-rMKL: a web server for dimensionality reduction and sample clustering of multi-view data based on unsupervised multiple kernel learning
2019-05-09

Abstract More and more affordable high-throughput techniques for measuring molecular features of biomedical samples have led to a huge increase in availability and size of different types of multi-omic datasets, containing, for example, genetic or histone modification data. Due to the multi-view characteristic of the data, established approaches for exploratory analysis are not directly applicable. Here we present web-rMKL, a web server that provides an integrative dimensionality reduction with subsequent clustering of samples based on data from multiple inputs. The underlying machine learning method rMKL-LPP performed best for clinical enrichment in a recent benchmark of state-of-the-art multi-view clustering algorithms. The method was introduced for a multi-omic cancer subtype discovery setting, however, it is not limited to this application scenario as exemplified by a presented use case for stem cell differentiation. web-rMKL offers an intuitive interface for uploading data and setting the parameters. rMKL-LPP runs on the back end and the user may receive notifications once the results are available. We also introduce a preprocessing tool for generating kernel matrices from tables containing numerical feature values. This program can be used to generate admissible input if no precomputed kernel matrices are available. The web server is freely available at web-rMKL.org.
Neuroticism Modulates the Functional Connectivity From Amygdala to Frontal Networks in Females When Avoiding Emotional Negative Pictures
2019-05-09

Amygdala activity was previously found to correlate with neuroticism as an effect of valence, but so far few studies have focused on motivational context. The network subserving altered amygdala activity has not yet been investigated although some studies showed strong effective connections with prefrontal cortex (PFC). The goal of this study was to test the modulatory role of neuroticism on the functional connectivity (FC) between amygdala and other brain regions, especially PFC, during emotion processing from motivational direction. We applied an emotional picture viewing paradigm with different motivational directions (approaching and avoiding) in a large participant sample. The results showed that neuroticism predicted the amount of amygdala FC to dorsomedial PFC (dmPFC) and middle cingulate cortex (MCC). Increased FC during negative vs. positive pictures was found primarily in low neuroticism subjects, especially during the avoid condition. This valence and motivation dependent connectivity increase were disrupted for high neurotic participants. No effect of neuroticism was found for the approach condition. We showed that neuroticism, especially in the context of passive affect regulation, may have impaired connectivity between amygdala and putative regulatory cortical networks.
Different rates of endocytic activity and vesicle transport from the apical and synaptic poles of the outer hair cell
2019-05-09

The larger endocytic fluorescent signals in the synaptic pole and the faster basoapical trafficking imply that membrane internalization and vesicle trafficking are more efficient at the synaptic pole than at the apical pole of the OHC.
Predictors of treatment response in type‐2 diabetes patients initiating basal‐supported oral therapy with insulin glargine 100 U/mL: A sub‐analysis of the Titration and OPtimisation (TOP) registry
2019-05-09

Abstract The aim of this study was to identify predictors of long‐term response to the initiation of basal‐supported oral therapy (BOT) with insulin glargine (IGlar‐100). Patients from the observational TOP registry were grouped based on those who had achieved (responders) and those who had not achieved (non‐responders) their HBA1c target and/or FBG ≤110 mg/dL 12 months after IGlar‐100 initiation. Independent predictors of treatment response were identified by regression analysis. Data for 2444 patients were analysed (responders, n = 1610; non‐responders, n = 834). Although the IGlar‐100 dose increase over 12 months was larger for non‐responders (+12.83 vs +9.46 U/d; P &lt; 0.0001), the corresponding decrease in HbA1c was smaller (−0.88% vs −1.57%). Independent predictors of response included lower BMI (OR, 0.97; 95% CI, 0.95‐1.00), lower FBG (OR, 0.98; 95% CI, 0.97‐0.98) and HbA1c values at baseline (OR, 0.24; 95% CI, 0.18‐0.31), a less ambitious HbA1c target (OR, 5.07; 95% CI, 3.37‐7.63) and bedtime administration of IGlar‐100 (OR, 1.55; 95% CI, 1.12‐2.14). In conclusion, HbA1c was the clinically most significant baseline characteristic predictive of response to BOT. This may suggest an advantage of IGlar‐100 initiation prior to excessive hyperglycaemia escalation.
Efficient merging of genome profile alignments
2019-05-09

Abstract Motivation Whole-genome alignment (WGA) methods show insufficient scalability toward the generation of large-scale WGAs. Profile alignment-based approaches revolutionized the fields of multiple sequence alignment construction methods by significantly reducing computational complexity and runtime. However, WGAs need to consider genomic rearrangements between genomes, which make the profile-based extension of several whole-genomes challenging. Currently, none of the available methods offer the possibility to align or extend WGA profiles. Results Here, we present genome profile alignment, an approach that aligns the profiles of WGAs and that is capable of producing large-scale WGAs many times faster than conventional methods. Our concept relies on already available whole-genome aligners, which are used to compute several smaller sets of aligned genomes that are combined to a full WGA with a divide and conquer approach. To align or extend WGA profiles, we make use of the SuperGenome data structure, which features a bidirectional mapping between individual sequence and alignment coordinates. This data structure is used to efficiently transfer different coordinate systems into a common one based on the principles of profiles alignments. The approach allows the computation of a WGA where alignments are subsequently merged along a guide tree. The current implementation uses progressiveMauve and offers the possibility for parallel computation of independent genome alignments. Our results based on various bacterial datasets up to several hundred genomes show that we can reduce the runtime from months to hours with a quality that is negligibly worse than the WGA computed with the conventional progressiveMauve tool. Availability and implementation GPA is freely available at https://lambda.informatik.uni-tuebingen.de/gitlab/ahennig/GPA. GPA is implemented in Java, uses progressiveMauve and offers a parallel computation of WGAs. Supplementary information Supplementary data are available at Bioinformatics online.
Preferential Consolidation of Emotional Memory During Sleep: A Meta-Analysis
2019-05-10

It is uncertain whether sleep preferentially consolidates emotional over neutral material. Some studies suggest that sleep enhances emotional memory (i.e., that there are large differences in strength of memory for valenced material compared to neutral material after a sleep-filled interval, but that this difference is smaller after a wake-filled interval). Others find no such effect. We attempted to resolve this uncertainty by conducting a meta-analysis that compared valenced to neutral material after both sleep- and wake-filled delays. Standard search strategies identified 31 studies (containing 36 separate datasets) that met our inclusion criteria. Using random effects modeling, we conducted separate analyses for datasets comparing (a) negative vs. neutral material, (b) positive vs. neutral material, or (c) combined negative and positive vs. neutral material. We then specified several subgroup analyses to investigate potential moderators of the relationship between sleep and emotional memory consolidation. Results showed no overall effect for preferential sleep-dependent consolidation of emotional over neutral material. However, moderation analyses provided evidence for stronger effects when (a) studies used free recall rather than recognition outcome measures, or (b) delayed recall or recognition outcomes were controlled for initial learning. Those analyses also suggested that other methodological features (e.g., whether participants experience a full night of sleep and a regular daytime waking control condition rather than a nap and a night-time sleep deprivation control condition) and sample characteristics (e.g. all-male or not, young adult or not) should be carefully addressed in future research in this field. These findings suggest that sleep does enhance emotional memory, but that in the laboratory the effect is only observed under particular methodological conditions. The conditions we identify as being critical to consider are consistent with general theories guiding scientific understanding of memory consolidation during sleep.
Organ Preservation in Rectal Cancer: The Patients' Perspective
2019-05-10

Organ preservation after a clinical complete response to radiochemotherapy is currently one of the most discussed topics in the management of rectal cancer. However, the patients' perspective has only been poorly studied so far. In this multicenter study, we examined 49 patients with locally advanced rectal cancer. The willingness to participate in an organ preservation study and the acceptance of the associated aspects such as intensified radiochemotherapy protocols, the need for close follow-up examinations and local regrowth rates were assessed. Attitudes were correlated with baseline quality of life parameters and psychological scales for "fear of progression", "locus of control", "depression", and the "willingness to take risks". A total of 83% of patients would consider the deferral of surgery in case of a clinical complete response (cCR). Three monthly follow-up studies and a 25% local regrowth rate are considered acceptable by 95% and 94% respectively. While 41% would be willing to exchange cure rates for a non-operative treatment strategy, a potentially more toxic radiochemotherapy in order to increase the probability of a cCR was the aspect with the lowest acceptance (55%). Psychological factors, in particular "locus of control" and "willingness to take risks", influenced patient preferences regarding most of the assessed parameters. While in general a broad acceptance of an organ-preserving treatment can be expected, patient preferences and concerns regarding different aspects of this strategy vary widely and require specific consideration during shared decision making.