julilili42/papers huggingface dataset:
Periorbital Reconstruction by “Periorbital Patch” Technique Using a Pericardium-Based Collagen Membrane and Titanium Mesh
2019-07-24

Objective: Titanium mesh is a commonly used material for the reconstruction of orbital floor fractures. However, in some instances, a subsequent inflammatory reaction can occur that causes the adhesion of orbital tissue to the titanium mesh. The adhesion of the orbital soft tissue to the mesh causes diplopia, lid rigidity and extraocular movements restriction. This study was performed to determine if the placement of a collagen membrane over a titanium mesh can prevent the adhesion of orbital soft tissue for an improved clinical outcome. Clinical considerations: A case study was performed investigating 106 patients undergoing a periorbital restoration. Seventy-two patients received a titanium mesh without a barrier membrane, 12 patients received a barrier membrane composed of autologous auricular cartilage to provide a barrier function and 22 patients received a pericardium collagen membrane and titanium mesh. Conclusions: Titanium has been shown to generate an intense inflammatory reaction in host tissues, which can cause fibrosis to adjacent structures. Fibrosis is an essential factor in the repair of fracture sites, however this can lead to adverse effects in the orbital socket. Fibrosis can cause cicatrization and lower eyelid retraction when induced along the lower orbital rim. An improved outcome can be achieved by using a barrier between the titanium mesh and the soft tissue, such as autogenous auricular cartilage, however, only patients treated with a resorbable collagen membrane to act as a soft tissue barricade during site regeneration, prevented the fibrosis reaction and related problems from occurring.
Report of first recurrent glioma patients examined with PET-MRI prior to re-irradiation
2019-07-24

PET-MRI provides radiation treatment planning imaging with high spatial and timely conformity for high-grade glioma patients treated with re-RT with potential advancements for target volume delineation. Prospective randomised trials are warranted to further investigate the treatment benefits of PET-MRI based re-RT planning.
Optimization of Rheological Behaviour and Skin Penetration of Thermogelling Emulsions with Enhanced Substantivity for Potential Application in Treatment of Chronic Skin Diseases
2019-07-24

Topical formulations are an important pillar in the therapy of skin diseases. Nevertheless, after application the formulation will be exposed to environmental effects. Contact with other surfaces will reduce the available amount of formulation and drug substance. The resulting consequences for therapy range from reduced effects to therapeutic failure. The removed active ingredient also contaminates patients’ environment. The aim of this work was to develop preparations that remain at the application site. These will enhance safety and efficiency and thus improve of skin disease therapies. Therefore, we developed polymer-stabilised emulsions that show thermogelling properties. Emulsions with different methyl cellulose concentrations and macrogols of different molecular weights were investigated. The dispersed phase consisted of nonivamide as the active pharmaceutical ingredient, dissolved in medium-chain triglycerides. Rheological properties, droplet size, substantivity and ex vivo penetration experiments were performed to characterise the developed formulations. Droplet size and rheological parameters were affected by the composition of the preparations. The tested formulations showed benefits in their substantivity compared to a conventional semi-solid cream. We found a residual amount of up to 100% at the application site. The drug levels in viable epidermis were in a therapeutic range. The developed emulsions are a promising vehicle to improve therapy for chronic skin diseases.
Structural control for the coordinated assembly into functional pathogenic type-3 secretion systems
2019-07-24

Abstract Functional injectisomes of the type-3 secretion system assemble into highly defined and stoichiometric bacterial molecular machines essential for infecting human and other eukaryotic cells. However, the mechanism that governs the regulated step-wise assembly process from the nucleation-phase, to ring-assembly, and the filamentous phase into a membrane embedded needle complex is unclear. We here report that the formation of a megadalton-sized needle complexes from Salmonella enterica serovar Typhimurium (SPI-1, Salmonella pathogenicity island-1) with proper stoichiometries is highly structurally controlled competing against the self-assembly propensity of injectisome components, leading to a highly unusual structurally-pleiotropic phenotype. The structure of the entire needle complex from pathogenic injectisomes was solved by cryo electron microscopy, focused refinements (2.5-4 Å) and co-variation analysis revealing an overall asymmetric arrangement containing cyclic, helical, and asymmetric sub-structures. The centrally located export apparatus assembles into a conical, pseudo-helical structure and provides a structural template that guides the formation of a 24-mer cyclic, surrounding ring, which then serves as a docking interface comprising three different conformations for sixteen N-terminal InvG subunits of the outer secretin ring. Unexpectedly, the secretin ring excludes the 16 th protein chain at the C-terminal outer ring, resulting in a pleiotropic 16/15-mer ring and consequently to an overall 24:16/15 basal body structure. Finally, we report how the transition from the pseudo-helical export apparatus into the helical filament is structurally resolved to generate the protein secretion channel, which provides the structural basis to restrict access of unfolded effector substrates. These results highlight the diverse molecular signatures required for a highly coordinated assembly process and provide the molecular basis for understanding triggering and transport of unfolded proteins through injectisomes.
Motor speech and non-motor language endophenotypes of Parkinson’s disease
2019-07-25

<b>Introduction</b>: Idiopathic Parkinson's Disease (PD) results in a range of motor and non-motor impairments. Clinical diagnosis commonly occurs after substantial neurophysiological damage limiting the opportunity for neuroprotective treatments. Uncovering sensitive objective markers with the capacity to detect pre-symptomatic disease and track disease progression is therefore a priority. Speech may provide an ideal proxy marker for PD; a quantifiable biometric that displays salient changes in early disease and appears to evolve with disease progression.<b>Areas covered</b>: This review describes the endophenotype of speech, voice, cognition and language modalities in PD and investigates the speech as a 'proxy marker' of PD disease state.<b>Expert opinion</b>: Detailed characterization at different disease stages are needed and must incorporate longitudinal assessment to capture small but significant changes in speech, voice, cognition and language modalities within patient changes over time. Advances in technology are leading to new opportunities for acquiring data remotely and more frequently, offering more ecologically valid testing environments. Combined with automated signal processing and analysis, symptoms may also be tracked in-home readily. Features extracted may provide a 'proxy marker' for early identification of PD and objective monitoring of disease progression.
One-Step ARMS-PCR for the Detection of SNPs—Using the Example of the PADI4 Gene
2019-07-25

In eukaryotes, cellular functions are tightly controlled by diverse post-translational modifications (PTMs) of proteins. One such PTM affecting many proteins is the deimination of arginine to citrulline. This process, called citrullination is catalyzed by a group of hydrolases called protein arginine deiminases (PADs), of which five isoforms have been identified. Hypercitrullination, as a result of increased PAD expression or activity, is associated with autoimmune diseases e.g., rheumatoid arthritis, lupus, Alzheimer’s disease, ulcerative colitis, multiple sclerosis, and certain cancers. Three common single nucleotide polymorphisms (SNPs) in the PADI4 gene have been described, namely rs874881, rs11203366, and rs11203367, which are thought to affect PAD4 expression and activity. We here compared the suitability of four methods for the screening of SNPs in the PADI4 gene: (i) SYBR-green based real-time polymerase chain reaction followed by high resolution melting curve analysis (HRM-PCR); (ii) PCR followed by detection of restriction fragment length polymorphisms (PCR-RFLP); (iii) conventional tetra-primer amplification refractory mutation system PCR (ARMS-PCR); and (iv) real-time PCR based on the one-step ARMS-PCR. Of these, ARMS-PCR proved to be the most suitable method regarding handling, duration, and cost of experiments. Using the method with SYBR-green based real-time PCR reagents further diminished handling steps and thus potential sources of error.
Orthostatic hypotension as a risk factor for longitudinal deterioration of cognitive function in the elderly
2019-07-25

Background and purpose Orthostatic hypotension is frequent with aging with a prevalence of 20%–30% in people aged 65 or older and is considered to increase the risk for coronary events, strokes and dementia. Our objective was to characterize the association of orthostatic hypotension and cognitive function longitudinally over 6 years in a large cohort of the elderly aged over 50 years. Methods In all, 495 participants were assessed longitudinally with the Schellong test and comprehensive cognitive testing using the extended CERAD neuropsychological test battery at baseline and after 6 years. In a subgroup of 92 participants, cerebral magnetic resonance imaging was evaluated for white matter changes using a modified version of the Fazekas score. Results The prevalence of orthostatic hypotension increases with aging reaching up to 30% in participants aged &gt;70 years. Participants with orthostatic hypotension presented with a higher vascular burden index (1.03 vs. 0.69, P ≤ 0.001), tended to have a higher prevalence of cerebral white matter hyperintensities (91.7% vs. 68.8%, P = 0.091) and showed a faster deterioration in executive and memory function (Trail Making Test B 95 vs. 87 s, P ≤ 0.001; word list learning sum −0.53 vs. 0.38, P = 0.002) compared to participants without orthostatic hypotension. Conclusion Orthostatic hypotension seems to be associated with cognitive decline longitudinally.
FLASHDeconv: Ultrafast, high-quality feature deconvolution for top-down proteomics
2019-07-25

Abstract Feature deconvolution, the determination of intact proteoform masses, is crucial for top-down proteomics, but currently suffers from long runtimes and quality issues. We present FLASHDeconv, an algorithm based on a simple transformation of mass spectra, which turns deconvolution into the search for constant patterns thus greatly accelerating the process. We show higher deconvolution quality and two to three orders of magnitude faster execution speed than existing approaches.
Rotation of polarization in the gravitational field of a laser beam—Faraday effect and optical activity
2019-07-25

Abstract We investigate the rotation of the polarization of a light ray propagating in the gravitational field of a circularly polarized laser beam. The rotation consists of a reciprocal part due to gravitational optical activity, and a non-reciprocal part due to the gravitational Faraday effect. We discuss how to distinguish the two effects: letting light propagate back and forth between two mirrors, the rotation due to gravitational optical activity cancels while the rotation due to the gravitational Faraday effect accumulates. In contrast, the rotation due to both effects accumulates in a ring cavity and a situation can be created in which gravitational optical activity dominates. Such setups amplify the effects by up to five orders of magnitude, which however is not enough to make them measurable with state of the art technology. The effects are of conceptual interest as they reveal gravitational spin–spin coupling in the realm of classical general relativity, a phenomenon which occurs in perturbative quantum gravity.
Towards a new reconstruction of past regional land-cover in Central Asia
2019-07-25

Land cover and land use influence the climate system from regional to global scales through biogeochemical (e.g. CO2) and biophysical (e.g. energy exchanges in the biosphere) feedbacks. Quantitative information about these changes are critical for accurate vegetation and climate modelling in order to quantify their impacts on the climate system. A long-term perspective (centuries to millennia) of changes in land cover and land use can be assessed by using pollen-based modelling approaches such as the REVEALS model. REVEALS estimates are now available for much of the northern Hemisphere. However, few data exist for the vast area in the centre of the Eurasian continent, the Central Asian steppes and piedmonts. Since this region is situated at the intersection between the major northern hemispheric climate subsystems, it is necessary to apply REVEALS to Central Asia in order to understand vegetation-climate feedbacks and dynamics on the world’s largest continent. Central Asia is characterized by a variety of environmental (deserts/steppes to forests) and topographical (ranging between 3000-7500 m for the highest peaks) factors that affect pollen-vegetation relationships and thereby REVEALS estimates. Available pollen records in this region substantially overestimate pollen types deriving from lowlands and steppe-like environments, in particular Artemisia and Chenopodiaceae taxa. Relative pollen productivity estimates (RPPs) of these taxa have been difficult to assess so far and correspond to a vast range of values. The greatest challenge for RPPs in this region include the selection of sites and approach to vegetation collection; the inclusion of different species into a unique pollen type and landscape characteristics may play an additional role. The present study explores the pollen-vegetation relationships of steppe- and desert-like plant taxa, focusing on Artemisia and Chenopodiaceae pollen types. The study area is located in the Ili River basin lowlands of southeast Kazakhstan. We undertook botanical survey, created vegetation maps and took modern pollen samples at thirty-seven randomly selected locations dominated by steppe- and desert-like vegetation within a radius of 55km. Here, we 1) discuss pollen taphonomy in terms of preservation, production, dispersion and deposition, 2) estimate the relevant source area for pollen and 3) calculate RPPs for the major plant taxa. We used the Extended R-value model coupled with the Lagrangian Stochastic Model (LSM) and Gaussian Plume Model (GPM) for modelling. RPP outcomes based on both LSM and GPM models are required to analyze the effects of wind-driven uphill transport and the differential vertical dispersion of pollen, as well as the long-distance transport of pollen in the mountain ranges of Central Asia, and therefore to get accurate land-cover reconstructions for this region of the northern Hemisphere.
A multiple proxy approach to reconstruct landscape-scale vegetation in steppe-like environments : a case study from southern Kazakhstan
2019-07-25

Assessing landscape-scale vegetation mosaics based on pollen data is a challenge. In temperate environments, vegetation mosaics primarily correspond to the relative proportions of grasslands, crops and different types of forest cover. In steppe-like environments such as those of Central Asia, these mosaics consider the relative proportions of grasslands, Artemisia steppes, Chenopodiaceae steppes and semi-deserts, riverbanks and land-use categories. Most of these land cover types reflect open and semi-open landscapes, which increases the difficulties to identify some types of mosaic patterns. This leads us to the questions: Do pollen assemblages provide reliable information about landscape mosaics in steppe-like environments? and Can a multiproxy approach help us to disentangle such information? To answer these questions, we conducted a vegetation study in the diverse semi-arid Ili River basin in southeast Kazakhstan. This area includes two national parks (Altyn Emel and Charyn Canyon) well known for their desert and canyon landscapes, biodiversity and red-listed species. It is characterized by a variety of desert, semi-desert and steppe landscapes. We sampled surface modern soils at 37 randomly selected locations within a radius of 55 km. At each site, we undertook botanical surveys within a 100 m radius from the soil samples following the protocol of the Crackles Bequest Project, as well as within a radius of 5 km from samples. A study of “relative pollen productivity estimates” is in progress. Maps of the major land cover types for the 37 sites have been created by using Sentinel-2 optical satellite images at a spatial resolution of 10 m, obtaining an iterative supervised classification approach within the remote sensing software SNAP. We extracted and analysed pollen, phytolith and biomarker assemblages from each soil sample. We compared the observed and proxy-based information using modelling and statistical methods. Indices of plant, pollen and phytolith composition and diversity, and biomarkers (distribution of GDGTs and n-alkanes in sediments), are used for comparison.
A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration
2019-07-26

Abstract Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or “wet” form of AMD, no therapy is successful for the non-neovascular or “dry” form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.
Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination
2019-07-26

See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees of central and peripheral involvement. Abnormal expression of Nfasc155 is accompanied by severe loss of myelinated fibres.
To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment
2019-07-26

OBJECTIVE The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery. METHODS Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma. RESULTS One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance. CONCLUSIONS In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.
Regulation of expression of drug-metabolizing enzymes by oncogenic signaling pathways in liver tumors: a review
2019-07-26

Mutations in genes encoding key players in oncogenic signaling pathways trigger specific downstream gene expression profiles in the respective tumor cell populations. While regulation of genes related to cell growth, survival, and death has been extensively studied, much less is known on the regulation of drug-metabolizing enzymes (DMEs) by oncogenic signaling. Here, a comprehensive review of the available literature is presented summarizing the impact of the most relevant genetic alterations in human and rodent liver tumors on the expression of DMEs with a focus on phases I and II of xenobiotic metabolism. Comparably few data are available with respect to DME regulation by p53-dependent signaling, telomerase expression or altered chromatin remodeling. By contrast, DME regulation by constitutive activation of oncogenic signaling <i>via</i> the RAS/RAF/mitogen-activated protein kinase (MAPK) cascade or <i>via</i> the canonical WNT/<i>β</i>-catenin signaling pathway has been analyzed in greater depth, demonstrating mostly positive-regulatory effects of WNT/<i>β</i>-catenin signaling and negative-regulatory effects of MAPK signaling. Mechanistic studies have revealed molecular interactions between oncogenic signaling and nuclear xeno-sensing receptors which underlie the observed alterations in DME expression in liver tumors. Observations of altered DME expression and inducibility in liver tumors with a specific gene expression profile may impact pharmacological treatment options.