julilili42/papers huggingface dataset:
Acceptability and usability of smartphone-based brainwave entrainment technology used by individuals with chronic pain in a home setting
2020-02-21

Background: Brainwave entrainment (BWE) using rhythmic visual or auditory stimulation has many potential clinical applications, including the management of chronic pain, where there is a pressing need for novel, safe and effective treatments. The aim of this study was to gain qualitative feedback on the acceptability and usability of a novel BWE smartphone application, to ensure it meets the needs and wishes of end users. Methods: Fifteen participants with chronic pain used the application at home for 4 weeks. Semi-structured telephone interviews were then carried out. A template analysis approach was used to interpret the findings, with an initial coding template structured around the constructs of a theoretical framework for assessing acceptability of healthcare interventions. Structured data analysis generated a final modified coding structure, capturing themes generated across participants’ accounts. Results: The four main themes were ‘approach to trying out the app: affective attitude and ethicality’, ‘perceived effectiveness’, ‘opportunity costs and burden’ and ‘intervention coherence and self-efficacy’. All participants were willing to engage with the technology and welcomed it as an alternative approach to medications. Participants appreciated the simplicity of design and the ability to choose between visual or auditory stimulation. All the participants felt confident in using the application. Conclusion: The findings demonstrate preliminary support for the acceptability and usability of the BWE application. This is the first qualitative study of BWE to systematically assess these issues.
The rise of Chemical Peeling in 19th‐century European Dermatology: emergence of agents, formulations and treatments
2020-02-21

Abstract Background Considering the increasing number of chemical peeling applications, also the interest in the history of chemical peelings and agents, has grown in dermatology. Research ascribes the first use of phenol as a chemical peeling agent to William Tilbury Fox (1836–1879) in 1871. Furthermore, Ferdinand von Hebra (1847–1902) is said to describe the properties of various peeling agents in 1874, and Paul Gerson Unna (1850–1929) adds resorcinol and trichloroacetic acid in 1882. Objective To identify the first mentions of chemical peeling applications and agents in 19th‐century dermatology. Methods Nineteenth‐century dermatologists were identified by an examination of literature of the last 30 years on the history of chemical peeling. Systematic examination of the medical textbooks of Hebra, Fox and Unna was conducted. It was proved whether the mentioned agents were used for chemical peeling applications. Results The skin peeling property of phenol was already discovered by its first describer, the chemist Friedlieb Ferdinand Runge (1795–1867) in 1834. The Viennese dermatologist Hebra described phenol as a chemical peeling agent in 1860. Hebra and his associate Moriz Kaposi (1837–1902) stated that ‘Lotio carbolica’ was already used in London. Fox used phenol mostly as a disinfectant and not for chemical peelings since 1869. Unna described the chemical peeling property of salicylic acid in 1882 and gave the most comprehensive account of chemical peels of the 19th century in 1899. Unna also introduced the Gutta‐percha plaster with salicylic acid and phenol. Around 1900, Unna was famous for his peeling paste with resorcinol in Germany. Conclusions A new chronology of the introduction of chemical peeling in dermatology can be drawn from the results. The German‐speaking dermatology pioneered the treatment of skin diseases with chemical peelings as well as for aesthetical purposes 21 years earlier than hitherto known.
Oleogels with Birch Bark Dry Extract: Extract Saving Formulations through Gelation Enhancing Additives
2020-02-21

Triterpenes from the outer bark of birch have many beneficial biological and pharmacological activities. In particular, its wound healing efficacy is of paramount importance. Apart from that, particles of a birch bark dry extract aggregate into a three dimensional network when they are dispersed in lipids yielding a semi-solid oleogel. However, gel formation requires high amounts of the extract, which then acts at once as the active ingredient and the gelling agent. Infrared spectra of the respective mixtures proved that hydrogen bonds play a crucial role in the formation of the gel network. Dicarboxylic acids had almost no effect on gel strength. Monoalcohols increased the firmness of the oleogel with a decreasing effect from methanol &gt; ethanol &gt; butanol &gt; octanol. All tested terminal diols increased the gel strength whereas vicinal diols affected the gel strength negatively. The effect was highly dependent on their concentration. The different effects of the diols are linked to their structure and polarity. The most pronounced enhancement of gelation was found for 1,6-hexanediol, which reduced the amount of triterpene extract (TE), which is necessary for the formation of an oleogel by a factor of 10.
Status and Contribution of CRISPR/Cas9 Based Gene-Editing System in the Development of a Low-Immunogenic Wheat Variety
2020-02-21

Gluten, a wheat protein, contains epitopes that trigger celiac disease (CD). So far, there is no treatment available for CD other than following a life-long, strict gluten-free diet (GFD). A very low-gluten or gluten-free wheat could provide an alternative treatment to CD. Till date, conventional plant breeding methods are not sufficient to produce celiac-safe wheat. Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9 (CRISPR/Cas9) is a versatile gene-editing system may efficiently edit the immunogenic gluten protein thereby producing a celiac-safe wheat variety. However, CRISPR/Cas9-mediated genome editing system has not been widely investigated to edit the wheat genome. Published literature available on various scientific platforms, that applied the CRISPR/Cas9 system to edit the wheat genome were explored. Only original research articles were included. Review articles, protocols, scientific presentations, and Ph.D. thesis were excluded. CRISPR/Cas9 is a highly specific gene-editing technology that can be used to efficiently edit the complex hexaploid wheat genome. It targets a specific wheat genome locus, delete an immunogenic gene and replace it with a preferred gene. CRISPR/Cas9 technology could be a breakthrough in providing an alternative treatment for CD. However, further studies are required to efficiently apply this gene-editing technology to develop a celiac-safe wheat variety.
Biological concepts in human sodium channel epilepsies and their relevance in clinical practice
2020-02-23

Abstract Objective Voltage‐gated sodium channels (SCNs) share similar amino acid sequence, structure, and function. Genetic variants in the four human brain‐expressed SCN genes SCN1A/2A/3A/8A have been associated with heterogeneous epilepsy phenotypes and neurodevelopmental disorders. To better understand the biology of seizure susceptibility in SCN ‐related epilepsies, our aim was to determine similarities and differences between sodium channel disorders, allowing us to develop a broader perspective on precision treatment than on an individual gene level alone. Methods We analyzed genotype‐phenotype correlations in large SCN ‐patient cohorts and applied variant constraint analysis to identify severe sodium channel disease. We examined temporal patterns of human SCN expression and correlated functional data from in vitro studies with clinical phenotypes across different sodium channel disorders. Results Comparing 865 epilepsy patients (504 SCN1A , 140 SCN2A , 171 SCN8A , four SCN3A , 46 copy number variation [CNV] cases) and analysis of 114 functional studies allowed us to identify common patterns of presentation. All four epilepsy‐associated SCN genes demonstrated significant constraint in both protein truncating and missense variation when compared to other SCN genes. We observed that age at seizure onset is related to SCN gene expression over time. Individuals with gain‐of‐function SCN2A/3A/8A missense variants or CNV duplications share similar characteristics, most frequently present with early onset epilepsy (&lt;3 months), and demonstrate good response to sodium channel blockers (SCBs). Direct comparison of corresponding SCN variants across different SCN subtypes illustrates that the functional effects of variants in corresponding channel locations are similar; however, their clinical manifestation differs, depending on their role in different types of neurons in which they are expressed. Significance Variant function and location within one channel can serve as a surrogate for variant effects across related sodium channels. Taking a broader view on precision treatment suggests that in those patients with a suspected underlying genetic epilepsy presenting with neonatal or early onset seizures (&lt;3 months), SCBs should be considered.
Investigating the temporal dynamics of electroencephalogram (EEG) microstates using recurrent neural networks
2020-02-24

Abstract Electroencephalogram (EEG) microstates that represent quasi‐stable, global neuronal activity are considered as the building blocks of brain dynamics. Therefore, the analysis of microstate sequences is a promising approach to understand fast brain dynamics that underlie various mental processes. Recent studies suggest that EEG microstate sequences are non‐Markovian and nonstationary, highlighting the importance of the sequential flow of information between different brain states. These findings inspired us to model these sequences using Recurrent Neural Networks (RNNs) consisting of long‐short‐term‐memory (LSTM) units to capture the complex temporal dependencies. Using an LSTM‐based auto encoder framework and different encoding schemes, we modeled the microstate sequences at multiple time scales (200–2,000 ms) aiming to capture stably recurring microstate patterns within and across subjects. We show that RNNs can learn underlying microstate patterns with high accuracy and that the microstate trajectories are subject invariant at shorter time scales (≤400 ms) and reproducible across sessions. Significant drop in the reconstruction accuracy was observed for longer sequence lengths of 2,000 ms. These findings indirectly corroborate earlier studies which indicated that EEG microstate sequences exhibit long‐range dependencies with finite memory content. Furthermore, we find that the latent representations learned by the RNNs are sensitive to external stimulation such as stress while the conventional univariate microstate measures (e.g., occurrence, mean duration, etc.) fail to capture such changes in brain dynamics. While RNNs cannot be configured to identify the specific discriminating patterns, they have the potential for learning the underlying temporal dynamics and are sensitive to sequence aberrations characterized by changes in metal processes. Empowered with the macroscopic understanding of the temporal dynamics that extends beyond short‐term interactions, RNNs offer a reliable alternative for exploring system level brain dynamics using EEG microstate sequences.
Dynamics of strongly coupled disordered dissipative spin-boson systems
2020-02-24

Spin-boson Hamiltonians are an effective description for numerous quantum few-and many-body systems such as atoms coupled to cavity modes, quantum electrodynamics in circuits and trapped ion systems. While reaching the limit of strong coupling is possible in current experiments, the understanding of the physics in this parameter regime remains a challenge, especially when disorder and dissipation are taken into account. Here we investigate a regime where the spin dynamics can be related to a Ising energy function defined in terms of the spin-boson couplings. While in the coherent weak coupling regime it is known that an effective description in terms of spin Hamiltonian is possible, we show that a similar viewpoint can be adopted in the presence of dissipation and strong couplings. The resulting dynamics features approximately thermal regimes, separated by out-of-equilibrium ones in which detailed balance is broken. Moreover, we show that under appropriately chosen conditions one can even achieve cooling of the spin degrees of freedom. This points towards the possibility of using strongly coupled dissipative spin-boson systems for engineering complex energy landscapes together with an appropriate cooling dynamics.
Intensity and dose of neuromuscular electrical stimulation influence sensorimotor cortical excitability
2020-02-24

Abstract Neuromuscular electrical stimulation (NMES) of the peripheral nervous system has been largely used in the field of neurorehabilitation to decrease muscle atrophy and to restore motor function in paralyzed patients. The rehabilitative effects of NMES rely on the direct or indirect efferent effect on muscle tone and afferent volleys that induce cortical excitation. Although different neuroimaging tools suggested the capability of NMES to regulate the excitability of sensorimotor cortex and corticospinal circuits, to date how intensity and dose of NMES can neuromodulate the brain oscillatory activity measured with electroencephalography (EEG) is yet to be clarified. In the present study, we quantify the effect of NMES parameters on brain oscillatory activity of twelve healthy participants who underwent stimulation of wrist extensors during rest while EEG was recorded. Three different NMES intensities were included: (1) low, inducing slight sensory perception, (2) medium, inducing moderate sensory perception, and (3) high, generating a functional movement. Firstly, we efficiently removed stimulation artifacts from the sensorimotor brain oscillatory activity. Secondly, we analyzed the effect of amplitude and dose on the latter. On the one hand, we observed significant NMES amplitude-dependent brain SMR modulation, demonstrating the direct effect of afferent receptors recruitment. On the other hand, our results revealed a significant NMES amplitude-based dose-effect on SMR modulation over time. While at low and medium intensities the NMES produced a significant cortical inhibitory effect in time, at high intensity a significant cortical facilitatory effect was induced. These results highlight the functionally relevant role of muscle contraction and proprioception in sensorimotor processes, which should be carefully considered for the design and development of NMES based neuromodulation.
Orthohepevirus C: An Expanding Species of Emerging Hepatitis E Virus Variants
2020-02-25

Hepatitis E virus (HEV) is an emerging zoonotic pathogen that has received an increasing amount of attention from virologists, clinicians, veterinarians, and epidemiologists over the past decade. The host range and animal reservoirs of HEV are rapidly expanding and a plethora of emerging HEV variants have been recently identified, some of which have the potential for interspecies infection. In this review, the detection of genetically diverse HEV variants, classified into and presumably associated with the species Orthohepevirus C, currently comprising HEV genotypes C1 and C2, by either serological or molecular approach is summarized. The distribution, genomic variability, and evolution of Orthohepevirus C are analyzed. Moreover, the potential risk of cross-species infection and zoonotic transmission of Orthohepevirus C are discussed.
Eikonal quasinormal modes of black holes beyond general relativity. II. Generalized scalar-tensor perturbations
2020-02-25

Black hole `spectroscopy', i.e. the identification of quasinormal mode\\nfrequencies via gravitational wave observations, is a powerful technique for\\ntesting the general relativistic nature of black holes. In theories of gravity\\nbeyond general relativity perturbed black holes are typically described by a\\nset of coupled wave equations for the tensorial field and the extra\\nscalar/vector degrees of freedom, thus leading to a theory-specific quasinormal\\nmode spectrum. In this paper we use the eikonal/geometric optics approximation\\nto obtain analytic formulae for the frequency and damping rate of the\\nfundamental quasinormal mode of a generalised, theory-agnostic system of\\nequations describing coupled scalar-tensor perturbations of spherically\\nsymmetric black holes. Representing an extension of our recent work, the\\npresent model includes a massive scalar field, couplings through the field\\nderivatives and first-order frame dragging rotational corrections. Moving away\\nfrom spherical symmetry, we consider the simple model of the scalar wave\\nequation in a general stationary-axisymmetric spacetime and use the eikonal\\napproximation to compute the quasinormal modes associated with equatorial and\\nnonequatorial photon rings.\\n
New variant in the IL1RN-gene (DIRA) associated with late-onset, CRMO-like presentation
2020-02-25

Abstract Objective To report a chronic recurrent multifocal osteomyelitis (CRMO)-like clinical phenotype with multisystem inflammation associated with a novel gene variant in the spectrum of IL-1-mediated diseases. Methods A 3-year-old boy presented with recurrent episodes of fever, serositis, pancreatitis and high inflammatory markers with onset at age 13 months. At age 3 years, he started limping. Imaging revealed multifocal pelvic bone inflammation suggestive of CRMO. Autoinflammation panel testing was non-contributory. Whole exome sequencing (WES) and advanced IL-1 pathway analysis was conducted. Results WES identified a novel homozygous interleukin receptor 1 (IL1RN) variant (c.62C&amp;gt;G; p. Ser21*) (NM_173842.2). Functional analysis of IL1RN mRNA and IL-1 receptor antagonist (IL-1RA) protein confirmed the diagnosis of a deficiency of the IL-1 receptor antagonist (DIRA). Treatment with the nonselective IL-1 inhibitor anakinra resulting in rapid remission; switch to the selective IL-1β antagonist canakinumab led to a flare within 6 weeks. Re-start of anakinra recaptured remission, last documented at the recent 19-month follow-up. Conclusion This is the first report of a novel late-onset DIRA confirmed by advanced diagnostic testing. In patients with systemic inflammation and CRMO-like bone lesions, IL1RN testing should be considered; even in the absence of skin manifestations. Non-selective IL-1 inhibition is an effective therapy.
Convergent evolution and possible constraint in the posterodorsal retraction of the external nares in pelagic crocodylomorphs
2020-02-25

Abstract Amongst Mesozoic marine reptiles, metriorhynchid crocodylomorphs were unique in evolving into pelagically adapted forms with little-to-no posterodorsal retraction of the external nares. Narial retraction is a common adaptation seen in sustained swimmers, notably occurring during cetacean evolution. Mesosaurids and the basalmost known members of ichthyosauriforms, thalattosaurians, saurosphargids, sauropterygians, pleurosaurids and mosasauroids had the external nares divided by an ossified bar, bound by multiple cranial bones and were positioned back from the tip of the rostrum. However, metriorhynchids evolved from taxa with a single external naris bound solely by the premaxilla, and positioned near the tip of an elongate rostrum. We posit that metriorhynchids were uniquely disadvantaged in evolving into sustained swimmers. Herein we describe three Late Jurassic metriorhynchid cranial rostra that display differing degrees of narial retraction. In our new phylogenetic analyses, the backwards migration of the narial fossa posterior margin occurred independently at least four times in Metriorhynchidae, whereas the backwards migration of the anterior margin only occurred twice. Although Rhacheosaurini share the backwards migration of the anterior and posterior narial margins, posterodorsal retraction occurred differently along three lineages. This culminated in the Early Cretaceous, where a rhacheosaurin evolved nares bound by the premaxilla and maxilla, and significantly posterodorsally retracted.
Metascience on Peer Review: Testing the Effects of a Study’s Originality and Statistical Significance in a Field Experiment
2020-02-25

Peer review has become the gold standard in scientific publishing as a selection method and a refinement scheme for research reports. However, despite its pervasiveness and conferred importance, relatively little empirical research has been conducted to document its effectiveness. Further, there is evidence that factors other than a submission’s merits can substantially influence peer reviewers’ evaluations. We report the results of a metascientific field experiment on the effect of the originality of a study and the statistical significance of its primary outcome on reviewers’ evaluations. The general aim of this experiment, which was carried out in the peer-review process for a conference, was to demonstrate the feasibility and value of metascientific experiments on the peer-review process and thereby encourage research that will lead to understanding its mechanisms and determinants, effectively contextualizing it in psychological theories of various biases, and developing practical procedures to increase its utility.
The Impact of Perceived Etiology, Treatment Type, and Wording of Treatment Information on the Assessment of Gastritis Treatments
2020-02-25

How patients assess the suitability of a certain therapy for treating a disease depends on a variety of influencing factors. Three key factors are people's subjective perceptions of a disease, the type of treatment, and the kind of communication used to convey information. The study presented here was a randomized controlled experiment in which we examined these three factors. We used a mixed design where we manipulated perceived etiology of gastritis (biopsychosocial vs. biomedical) as a between-group factor, and treatment type (behavioral vs. pharmacological) and wording of treatment information (holistic vs. scientific) as within-group factors. We found that gastritis treatments that matched the perceived etiology of the illness were assessed to be more effective. Moreover, treatments that matched the perceived etiology enhanced participants' intention to undergo the treatment themselves and their willingness to recommend it to a person close to them. Finally, participants' intention to undergo the treatment was also enhanced when the wording of the treatment information matched the perceived etiology. We discuss the implications of our findings in terms of health communication and patient education.
MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma
2020-02-26

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients’ responses to ICI and survival. Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of &gt;50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or &lt;1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.