julilili42/papers huggingface dataset:
Auditory Threshold Variability in the SAMP8 Mouse Model of Age-Related Hearing Loss: Functional Loss and Phenotypic Change Precede Outer Hair Cell Loss
2021-08-02

Age-related hearing loss (ARHL) is the most common sensory deficit in aging society, which is accompanied by increased speech discrimination difficulties in noisy environments, social isolation, and cognitive decline. The audiometric degree of ARHL is largely correlated with sensory hair cell loss in addition to age-related factors not captured by histopathological analysis of the human cochlea. Previous studies have identified the senescence-accelerated mouse prone strain 8 (SAMP8) as a model for studying ARHL and age-related modifications of the cochlear redox environment. However, the SAMP8 population exhibits a large variability in auditory function decline over age, whose underlying cause remains unknown. In this study, we analyzed auditory function of SAMP8 mice by measuring auditory brainstem response (ABR) thresholds at the age of 6 weeks (juvenile), 12 weeks (young adult), and 24 weeks (adult). Consistent with previous studies, SAMP8 mice exhibit an early progressive, age-related decline of hearing acuity. However, a spatiotemporal cytohistological analysis showed that the significant increase in threshold variability was not concurrently reflected in outer hair cell (OHC) loss observed in the lower and upper quartiles of the ABR threshold distributions over age. This functional loss was found to precede OHC loss suggesting that age-related phenotypic changes may be contributing factors not represented in cytohistological analysis. The expression of potassium channels KCNQ4 (K V 7.4), which mediates the current I K,n crucial for the maintenance of OHC membrane potential, and KCNQ1 (K V 7.1), which is an essential component in potassium circulation and secretion into the endolymph generating the endocochlear potential, showed differences between these quartiles and age groups. This suggests that phenotypic changes in OHCs or the stria vascularis due to variable oxidative deficiencies in individual mice may be predictors of the observed threshold variability in SAMP8 mice and their progressive ARHL. In future studies, further phenotypic predictors affected by accumulated metabolic challenges over age need to be investigated as potentially underlying causes of ARHL preceding irreversible OHC loss in the SAMP8 mouse model.
Testing the weak-equivalence principle near black holes
2021-08-02

Today we have quite stringent constraints on possible violations of the Weak\\nEquivalence Principle from the comparison of the acceleration of test-bodies of\\ndifferent composition in Earth's gravitational field. In the present paper, we\\npropose a test of the Weak Equivalence Principle in the strong gravitational\\nfield of black holes. We construct a relativistic reflection model in which\\neither the massive particles of the gas of the accretion disk or the photons\\nemitted by the disk may not follow the geodesics of the spacetime. We employ\\nour model to analyze the reflection features of a NuSTAR spectrum of the black\\nhole binary EXO 1846-031 and we constrain two parameters that quantify a\\npossible violation of the Weak Equivalence Principle by massive particles and\\nX-ray photons, respectively.\\n
Mucoadhesion and Mucopenetration of Cannabidiol (CBD)-Loaded Mesoporous Carrier Systems for Buccal Drug Delivery
2021-08-02

Transmucosal drug delivery represents a promising noninvasive option when drugs are employed which have a low oral bioavailability like CBD. However, this concept can only be successful as long as the formulation provides sufficient buccal retention and mucosal penetration. In this study, mucoadhesive carrier systems were evaluated consisting of CBD-loaded silica (Aeroperl 300) carriers, mucoadhesive polymers (Hypromellose (HPMC), chitosan and carbomer) and propylene glycol as a penetration enhancer. Mucoadhesive effect, drug release and penetration ability were evaluated for each carrier system. The results show that the addition of HPMC and carbomer substantially improve mucoadhesion compared to pure CBD, with an increase of 16-fold and 20-fold, respectively. However, due to their strong swelling, HPMC and carbomer hinder the penetration of CBD and rely on co-administration of propylene glycol as an enhancer to achieve sufficient mucosal absorption. Chitosan, on the other hand, achieves an 8-fold increase in mucoadhesion and enhances the amount of CBD absorbed by three times compared to pure CBD. Thus, chitosan represents a promising polymer to combine both effects. Considering the results, the development of silica-based buccal drug delivery systems is a promising approach for the effective delivery of CBD.
Captive great apes tend to innovate simple tool behaviors quickly
2021-08-02

Abstract Recent studies have highlighted the important role that individual learning mechanisms and different forms of enhancenment play in the acquisition of novel behaviors by naïve individuals. A considerable subset of these studies has focused on tool innovation by our closest living relatives, the great apes, to better undestand the evolution of technology in our own lineage. To be able to isolate the role that individual learning plays in great ape tool innovation, researchers usually employ what are known as baseline tests. Although these baselines are commonly used in behavioral studies in captivity, the length of these tests in terms of number of trials and duration remains unstandarized across studies. To address this methodological issue, we conducted a literature review of great ape tool innovation studies conducted in zoological institutions and compiled various methodological data including the timing of innovation. Our literature review revealed an early innovation tendency in great apes, which was particularly pronounced when simple forms of tool use were investigated. In the majority of experiments where tool innovation took place, this occurred within the first trial and/or the first hour of testing. We discuss different possible sources of variation in the latency to innovate such as testing setup, species and task. We hope that our literature review helps researchers design more data‐informed, resource‐efficient experiments on tool innovation in our closest living relatives.
Fully automated whole-liver volume quantification on CT-image data: Comparison with manual volumetry using enhanced and unenhanced images as well as two different radiation dose levels and two reconstruction kernels
2021-08-02

Objectives To evaluate the accuracy of fully automated liver volume quantification vs. manual quantification using unenhanced as well as enhanced CT-image data as well as two different radiation dose levels and also two image reconstruction kernels. Material and methods The local ethics board gave its approval for retrospective data analysis. Automated liver volume quantification in 300 consecutive livers in 164 male and 103 female oncologic patients (64±12y) performed at our institution (between January 2020 and May 2020) using two different dual-energy helicals: portal-venous phase enhanced, ref. tube current 300mAs (CARE Dose4D) for tube A (100 kV) and ref. 232mAs tube current for tube B (Sn140kV), slice collimation 0.6mm, reconstruction kernel I30f/1, recon. thickness of 0.6mm and 5mm, 80–100 mL iodine contrast agent 350 mg/mL, (flow 2mL/s) and unenhanced ref. tube current 100mAs (CARE Dose4D) for tube A (100 kV) and ref. 77mAs tube current for tube B (Sn140kV), slice collimation 0.6mm (kernel Q40f) were analyzed. The post-processing tool ( syngo .CT Liver Analysis) is already FDA-approved. Two resident radiologists with no and 1-year CT-experience performed both the automated measurements independently from each other. Results were compared with those of manual liver volume quantification using the same software which was supervised by a senior radiologist with 30-year CT-experience (ground truth). Results In total, a correlation of 98% was obtained for liver volumetry based on enhanced and unenhanced data sets compared to the manual liver quantification. Radiologist #1 and #2 achieved an inter-reader agreement of 99.8% for manual liver segmentation (p&lt;0.0001). Automated liver volumetry resulted in an overestimation (&gt;5% deviation) of 3.7% for unenhanced CT-image data and 4.0% for contrast-enhanced CT-images. Underestimation (&lt;5%) of liver volume was 2.0% for unenhanced CT-image data and 1.3% for enhanced images after automated liver volumetry. Number and distribution of erroneous volume measurements using either thin or thick slice reconstructions was exactly the same, both for the enhanced as well for the unenhanced image data sets (p&gt; 0.05). Conclusion Results of fully automated liver volume quantification are accurate and comparable with those of manual liver volume quantification and the technique seems to be confident even if unenhanced lower-dose CT image data is used.
Permanent Dipole Moments Enhance Electronic Coupling and Singlet Fission in Pentacene
2021-08-02

Singlet fission (SF), the photophysical process in which one singlet exciton is transformed into two triplets, depends <i>inter alia</i> on the coupling of electronic states. Here, we use fluorination and the resulting changes in partial charge distribution across the chromophore backbone as a particularly powerful tool to control this parameter in pentacene. We find that the introduction of a permanent dipole moment leads to an enhanced coupling of Frenkel exciton and charge transfer states and to an increased SF rate which we probed using ultrafast transient absorption spectroscopy. These findings are contrasted with H-aggregate formation and a significantly reduced triplet-pair state lifetime in a fluorinated pentacene for which the different partial charge distribution leads to a negligible dipole moment.
Visual Analysis of Large‐Scale Protein‐Ligand Interaction Data
2021-08-02

Abstract When studying protein‐ligand interactions, many different factors can influence the behaviour of the protein as well as the ligands. Molecular visualisation tools typically concentrate on the movement of single ligand molecules; however, viewing only one molecule can merely provide a hint of the overall behaviour of the system. To tackle this issue, we do not focus on the visualisation of the local actions of individual ligand molecules but on the influence of a protein and their overall movement. Since the simulations required to study these problems can have millions of time steps, our presented system decouples visualisation and data preprocessing: our preprocessing pipeline aggregates the movement of ligand molecules relative to a receptor protein. For data analysis, we present a web‐based visualisation application that combines multiple linked 2D and 3D views that display the previously calculated data The central view, a novel enhanced sequence diagram that shows the calculated values, is linked to a traditional surface visualisation of the protein. This results in an interactive visualisation that is independent of the size of the underlying data, since the memory footprint of the aggregated data for visualisation is constant and very low, even if the raw input consisted of several terabytes.
Exponentially Accelerated Approach to Stationarity in Markovian Open Quantum Systems through the Mpemba Effect
2021-08-02

Ergodicity-breaking and slow relaxation are intriguing aspects of nonequilibrium dynamics both in classical and in quantum settings. These phenomena are typically associated with phase transitions, e.g. the emergence of metastable regimes near a first-order transition or scaling dynamics in the vicinity of critical points. Despite being of fundamental interest the associated divergent time scales are a hindrance when trying to explore steady-state properties. Here we show that the relaxation dynamics of Markovian open quantum systems can be accelerated exponentially by devising an optimal unitary transformation that is applied to the quantum system immediately before the actual dynamics. This initial "rotation" is engineered in such a way that the state of the quantum system becomes orthogonal to the slowest decaying dynamical mode. We illustrate our idea -- which is inspired by the so-called Mpemba effect, i.e., water freezing faster when initially heated up -- by showing how to achieve an exponential speed-up in the convergence to stationarity in Dicke models, and how to avoid metastable regimes in an all-to-all interacting spin system.
Cryoturbation leads to iron-organic carbon associations along a permafrost soil chronosequence in northern Alaska
2021-08-02

In permafrost soils, substantial amounts of organic carbon (OC) are potentially protected from microbial degradation and transformation into greenhouse gases by association with reactive iron (Fe) minerals. As permafrost environments respond to climate change, increased drainage of thaw lakes in permafrost regions is predicted. Soils will subsequently develop on these drained thaw lakes, but the role of Fe-OC associations in future OC stabilization during this predicted soil development is unknown. To fill this knowledge gap, we have examined Fe-OC associations in organic, cryoturbated and mineral horizons along a 5500-year chronosequence of drained thaw lake basins in Utqiaġvik, Alaska. By applying chemical extractions, we found that ~17 % of the total OC content in cryoturbated horizons is associated with reactive Fe minerals, compared to ~10 % in organic or mineral horizons. As soil development advances, the total stocks of Fe-associated OC more than double within the first 50 years after thaw lake drainage, because of increased storage of Fe-associated OC in cryoturbated horizons (from 8 to 75 % of the total Fe-associated OC stock). Spatially-resolved nanoscale secondary ion mass spectrometry showed that OC is primarily associated with Fe(III) (oxyhydr)oxides which were identified by 57Fe Mössbauer spectroscopy as ferrihydrite. High OC:Fe mass ratios (&gt;0.22) indicate that Fe-OC associations are formed via co-precipitation, chelation and aggregation. These results demonstrate that, given the proposed enhanced drainage of thaw lakes under climate change, OC is increasingly incorporated and stabilized by the association with reactive Fe minerals as a result of soil formation and increased cryoturbation.
Strong Suppression of Thermal Conductivity in the Presence of Long Terminal Alkyl Chains in Low‐Disorder Molecular Semiconductors
2021-08-03

Abstract While the charge transport properties of organic semiconductors have been extensively studied over the recent years, the field of organics‐based thermoelectrics is still limited by a lack of experimental data on thermal transport and of understanding of the associated structure–property relationships. To fill this gap, a comprehensive experimental and theoretical investigation of the lattice thermal conductivity in polycrystalline thin films of dinaphtho[2,3‐b:2′,3′‐f]thieno[3,2‐b]thiophene (C n ‐DNTT‐C n with n = 0, 8) semiconductors is reported. Strikingly, thermal conductivity appears to be much more isotropic than charge transport, which is confined to the 2D molecular layers. A direct comparison between experimental measurements (3ω–Völklein method) and theoretical estimations (approach‐to‐equilibrium molecular dynamics (AEMD) method) indicates that the in‐plane thermal conductivity is strongly reduced in the presence of the long terminal alkyl chains. This evolution can be rationalized by the strong localization of the intermolecular vibrational modes in C8‐DNTT‐C8 in comparison to unsubstituted DNTT cores, as evidenced by a vibrational mode analysis. Combined with the enhanced charge transport properties of alkylated DNTT systems, this opens the possibility to decouple electron and phonon transport in these materials, which provides great potential for enhancing the thermoelectric figure of merit ZT .
A new latest Cretaceous pleurodiran turtle (Testudinata: Dortokidae) from the Haţeg Basin (Romania) documents end-Cretaceous faunal provinciality and selective survival during the K-Pg extinction
2021-08-03

Dortokidae is an endemic family of stem-pleurodiran turtles, known exclusively from the Cretaceous and early Paleogene of Europe. Here we describe a new dortokid taxon from the Upper Cretaceous (Maastrichtian) Sînpetru Formation of the southern Haţeg Basin, Romania. The type material of Dortoka vremiri sp. nov. comprises a well-preserved carapace and a nearly complete plastron as well as the in situ right scapula and right pubis. Phylogenetic analyses performed to assess the position and interrelationships of Dortoka vremiri sp. nov. within Dortokidae as well as within the wider Pleurodira recovered the new taxon firmly nested within Dortokidae, and together with other dortokids, placed along the stem lineage of pleurodires. Our analysis provides evidence for allopatric speciation in Dortoka through the presence of two distinct lineages – an eastern and a western European lineage, respectively. A similar east/west disjunct distribution pattern has also been established previously for several vertebrate groups such as other turtles, dinosaurs and mammals, probably resulting from isolation due to the particular palaeogeographical setting of the Late Cretaceous European Archipelago. The phylogeny demonstrates local survival of Dortoka across the K-Pg boundary as the sister-taxon of D. vremiri is D. botanica from the uppermost Paleocene deposits of Romania and points to geographical selectivity, as the western lineage of Dortoka went extinct before the Paleogene. Osteology and novel taphonomical data imply a semi-terrestrial lifestyle for Kallokibotion bajazidi, a turtle occurring in coeval faunas with the aquatic and smaller-sized D. vremiri and most likely going extinct at the K-Pg boundary. Altogether, this pattern is consistent with selective extinction of terrestrial taxa previously observed for other continental vertebrate assemblages across the end-Cretaceous mass extinction with only two other examples from turtles.http://zoobank.org/urn:lsid:zoobank.org:pub:871AD436-9448-40C6-85A4-0213CBC04A29
Chemical Gradients of Plant Substrates in an Atta texana Fungus Garden
2021-08-03

The study of complex ecosystems requires an understanding of the chemical processes involving molecules from several sources. Some of the molecules present in fungus-growing ants’ symbiotic system originate from plants.
Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study
2021-08-04

Objective Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. Methods We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015–2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. Results Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty‐five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty‐two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty‐four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). Conclusion Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.
Burkholderia in the genomic era: from taxonomy to the discovery of new antimicrobial secondary metabolites
2021-08-04

Species of <i>Burkholderia</i> are highly versatile being found not only abundantly in soil, but also as plants and animals' commensals or pathogens. Their complex multireplicon genomes harbour an impressive number of polyketide synthase (PKS) and nonribosomal peptide-synthetase (NRPS) genes coding for the production of antimicrobial secondary metabolites (SMs), which have been successfully deciphered by genome-guided tools. Moreover, genome metrics supported the split of this genus into <i>Burkholderia sensu stricto</i> (s.s.) and five new other genera. Here, we show that the successful antimicrobial SMs producers belong to <i>Burkholderia</i> s.s. Additionally, we reviewed the occurrence, bioactivities, modes of action, structural, and biosynthetic information of thirty-eight <i>Burkholderia</i> antimicrobial SMs shedding light on their diversity, complexity, and uniqueness as well as the importance of genome-guided strategies to facilitate their discovery. Several <i>Burkholderia</i> NRPS and PKS display unusual features, which are reflected in their structural diversity, important bioactivities, and varied modes of action. Up to now, it is possible to observe a general tendency of <i>Burkholderia</i> SMs being more active against fungi. Although the modes of action and biosynthetic gene clusters of many SMs remain unknown, we highlight the potential of <i>Burkholderia</i> SMs as alternatives to fight against new diseases and antibiotic resistance.
Vitreoretinal Lymphoma
2021-08-04

Vitreoretinal lymphoma (VRL) is a rare variant of primary central nervous system lymphoma (PCNSL), mostly of diffuse large B cell lymphoma, which affects the retina and/or the vitreous with or without optic nerve involvement. The disease course is aggressive. Up to 90% of the patients develop central nervous system lymphoma within one year. The diagnosis of VRL is challenging due to nonspecific chronic and relapsing uveitis and is made by anterior chamber tab or vitreous aspirate biopsy. There is no established treatment protocol for VRL patients with bilateral involvement without CNS involvement. There are suggestions to use only intravitreal chemotherapy with methotrexate and/or rituximab. Alternatively, systemic high-dose MTX treatment or external beam radiotherapy is used. Further studies are needed to prove and confirm the prophylactic systemic therapy in preventing CNS involvement in limited VRL.
Evaluation of Long-term Clearance Rates of Interventions for Actinic Keratosis
2021-08-04

This systematic review and network meta-analysis found that therapy including ALA-PDT, imiquimod, 5%, MAL-PDT, and cryosurgery was associated with significant long-term efficacy in the NMA. This study provides data for a possible use in an evidence-based framework for selecting interventions with sustained lesion clearance.