julilili42/papers huggingface dataset:
Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia
2020-11-20

Abstract Introduction The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data‐driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure‐function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non‐carriers, and increased with proximity to the expected onset of disease. Discussion Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.
New insights in the coordinated amidase and glucosaminidase activity of the major autolysin (Atl) in Staphylococcus aureus
2020-11-20

Abstract After bacterial cell division, the daughter cells are still covalently interlinked by the peptidoglycan network which is resolved by specific hydrolases (autolysins) to release the daughter cells. In staphylococci, the major autolysin (Atl) with its two domain enzymes, N-acetylmuramyl-L-alanine amidase (AmiA) and β-N-acetylglucosaminidase (GlcA), resolves the peptidoglycan to release the daughter cells. Internal deletions in each of the enzyme domains revealed defined morphological alterations such as cell cluster formation in Δ amiA , Δ glcA and Δ atl , and asymmetric cell division in the Δ glcA . A most important finding was that GlcA activity requires the prior removal of the stem peptide by AmiA for its activity thus the naked glycan strand is its substrate. Furthermore, GlcA is not an endo -β-N-acetylglucosaminidase but an exo -enzyme that cuts the glycan backbone to disaccharides independent of its O -acetylation modification. Our results shed new light into the sequential peptidoglycan hydrolysis by AmiA and GlcA during cell division in staphylococci.
Lepton-jet correlation in deep inelastic scattering
2020-11-20

We study the lepton-jet correlation in deep inelastic scattering. We perform\\none-loop calculations for the spin averaged and transverse spin dependent\\ndifferential cross sections depending on the total transverse momentum of the\\nfinal state lepton and the jet. The transverse momentum dependent (TMD)\\nfactorization formalism is applied to describe the relevant observables. To\\nshow the physics reach of this process, we perform a phenomenological study for\\nHERA kinematics and comment on an ongoing analysis of experimental data. In\\naddition, we highlight the potential of this process to constrain small- \\ndynamics.\\n
Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotic Drugs
2020-11-20

Background: The use of therapeutic drug monitoring (TDM) to guide treatment with long-acting injectable (LAI) antipsychotics, which are increasingly prescribed, remains a matter of debate. The aim of this review was to provide a practical framework for the integration of TDM when switching from an oral formulation to the LAI counterpart, and in maintenance treatment. Methods: The authors critically reviewed 3 types of data: (1) positron emission tomography data evaluating dopamine (D2/D3) receptor occupancy related to antipsychotic concentrations in serum or plasma; D2/D3 receptors are embraced as target sites in the brain for antipsychotic efficacy and tolerability, (2) pharmacokinetic studies evaluating the switch from oral to LAI antipsychotics, and (3) pharmacokinetic data for LAI formulations. Based on these data, indications for TDM and therapeutic reference ranges were considered for LAI antipsychotics. Results: Antipsychotic concentrations in blood exhibited interindividual variability not only under oral but also under LAI formulations because these concentrations are affected by demographic characteristics such as age and sex, genetic peculiarities, and clinical variables, including comedications and comorbidities. Reported data combined with positron emission tomography evidence indicated a trend toward lower concentrations under LAI administration than under oral medications. However, the available evidence is insufficient to recommend LAI-specific therapeutic reference ranges. Conclusions: Although TDM evidence for newer LAI formulations is limited, this review suggests the use of TDM when switching an antipsychotic from oral to its LAI formulation. The application of TDM practice is more accurate for dose selection than the use of dose equivalents as it accounts more precisely for individual characteristics.
Bioavailable Environmental Pollutant Patterns in Sediments from Passive Equilibrium Sampling
2020-11-20

Sediment-associated risks depend on the bioavailable fraction of organic chemicals and cannot be comprehended by their total concentrations. The present study investigated contamination patterns of bioavailable chemicals in sediments from various sites around the globe by using passive equilibrium sampling. The extracts had been characterized previously for mixture effects by in vitro reporter gene assays and were in this study analyzed using gas chromatography-high resolution mass spectrometry for 121 chemicals including both legacy and emerging contaminants. The spatial distribution of the detected chemicals revealed distinct contamination patterns among sampling sites. We identified compounds in common at the different sites but most contaminant mixtures were site-specific. The mixture effects of the detected chemicals were predicted with a mixture toxicity model from effect concentrations of bioactive single chemicals and detected concentrations, applying a joint model for concentration addition and independent action. The predicted mixture effects were dominated by polycyclic aromatic hydrocarbons, and among the chemicals with available effect data, 17% elicited oxidative stress response and 18% activated the arylhydrocarbon receptor. Except for two sites in Sweden, where 11 and 38% of the observed oxidative stress response were explained by the detected chemicals, less than 10% of effects in both biological end points were explained. These results provide a comprehensive investigation of bioavailable contamination patterns of sediments and may serve as an example of employing passive equilibrium sampling as a monitoring technique to integrate the risk of bioavailable sediment-associated chemicals in aquatic environments.
FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma
2020-11-20

Abstract Background Fibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear. Methods We performed RT-PCR in 101 glioblastoma samples to detect FGFR3-TACC3 fusions (“RT-PCR cohort”) and correlated results with FGFR3 immunohistochemistry (IHC). Further, we applied FGFR3 IHC in 552 tissue microarray glioma samples (“TMA cohort”) and validated these results in two external cohorts with 319 patients. Gene panel sequencing was carried out in 88 samples (“NGS cohort”) to identify other possible FGFR3 alterations. Molecular modeling was performed on newly detected mutations. Results In the “RT-PCR cohort,” we identified FGFR3-TACC3 fusions in 2/101 glioblastomas. Positive IHC staining was observed in 73/1024 tumor samples of which 10 were strongly positive. In the “NGS cohort,” we identified FGFR3 fusions in 9/88 cases, FGFR3 amplification in 2/88 cases, and FGFR3 gene mutations in 7/88 cases in targeted sequencing. All FGFR3 fusions and amplifications and a novel FGFR3 K649R missense mutation were associated with FGFR3 overexpression (sensitivity and specificity of 93% and 95%, respectively, at cutoff IHC score &amp;gt; 7). Modeling of these data indicated that Tyr647, a residue phosphorylated as a part of FGFR3 activation, is affected by the K649R mutation. Conclusions FGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.
Ventricular assist device for a coronavirus disease 2019‐affected heart
2020-11-20

Abstract Coronavirus disease 2019 (COVID‐19) is challenging the care for cardiovascular patients, resulting in serious consequences with increasing mortality in pre‐diseased heart failure patients. In the current state of the pandemic, the physiopathology of COVID‐19 affecting pre‐diseased hearts and the management of terminal heart failure in COVID‐19 patients remain unclear. We outline the findings of a young COVID‐19 patient suffering from idiopathic cardiomyopathy who was treated for acute multi‐organ failure and required cardiac surgery with implantation of a temporary right ventricular and durable left ventricular assist device (LVAD). For deeper translational insights, we used in‐depth tissue analysis by electron and light sheet fluorescence microscopy revealing evidence for spatial distribution of severe acute respiratory syndrome coronavirus 2 in the heart. This indicates that in‐depth analysis may represent a valuable tool in understanding indistinct clinical cases. We conclude that COVID‐19 directly affects pre‐diseased hearts, but the consequences can be treated successfully with LVAD implantation.
Investigations on Alkanediols as Alternative Preservatives in a Nonionic Hydrophilic Cream
2020-11-20

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect of four different alkanediols, namely 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol, and 1,2-octanediol on the physical stability of a nonionic hydrophilic cream was investigated. Further, the incorporation of the alkanediols into lamellar structures of the cream was evaluated using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) measurements. The interaction with the mixed crystals of the cream was found to increase with raising alkyl chain length of the added alkanediol. As a result, consistency and stability of the cream are slightly impaired. A test for efficacy of antimicrobial preservation according to the European Pharmacopoeia (Ph.Eur.) revealed that the antimicrobial activity is directly linked to the length of the alkyl chain of the alkanediols. 2-Methyl-2,4-pentanediol differs from both findings. This compound has non-vicinal hydroxy groups which result in a reduced amphiphilicity compared to the others. Consequently, it has a smaller impact on the colloidal structure of the cream and shows a comparatively low antimicrobial activity.
Coiled-coil and RPW8-type immune receptors function at the plasma membrane in a phospholipid dependent manner
2020-11-20

Abstract Activation of intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) results in immunity and a localized cell death response of infected cells. Cell death activity of many NLRs requires oligomerization and in some cases plasma membrane (PM) localization. However, the exact mechanisms underlying PM localization of NLRs lacking recognizable N- or C-terminal lipidation motifs or predicted transmembrane domains remains elusive. Here we show that the PM localization and stability of members of the RPW8-like coiled-coil (CC R ) domain NLRs (RNLs) and a CC-type NLR (CNL) depend on the interaction with PM phospholipids. Depletion of phosphatidylinositol-4-phosphate (PI4P) from the PM led to a mislocalization of the analyzed NLRs and consequently inhibited their cell death activity. We further demonstrate activation-dependent self-association of cell death inducing RNLs. Our results provide new insights into the molecular mechanism of NLR PM localization and defines an important role of phospholipids for CNL and RNL activity during immunity.
Rational Drug Repurposing: Focus on Lysosomotropism, Targets in Disease Process, Drug Profile, and Pulmonary Tissue Accumulation in SARS-CoV-2 Infection/COVID-19
2020-11-20

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the disease-causing pathogen of Coronavirus disease 2019 (COVID-19). (Pre)clinical research to identify rapidly available small molecules for the treatment of SARS-CoV-2 infections/COVID-19 has focused to date on the approved lysosomotropic antimalarials chloroquine and hydroxychloroquine, the investigational remdesivir (GS-5734, compassionate use), and the anti-inflammatory corticosteroid dexamethasone (COVID-19 Treatment Guidelines Panel, 2020). Lopinavir/ritonavir and other HIV protease inhibitors, however, were discontinued as treatment options in COVID-19 demonstrating no clinical benefit in clinical trials. Despite encouraging results in treating hospitalized patients with COVID-19 requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) with remdesivir and dexamethasone, there is still a lack of active compounds exhibiting pan-coronavirus antiviral activity, tackling or preventing host cell infection, forming syncytia, endotheliitis, or the cytokine release syndrome (CRS)/cytokine storm syndrome in COVID-19. Target-oriented and in particular site of action-oriented drug repurposing of small molecules has the potential to close the gap in prophylaxis and treatment of mild and moderate COVID-19 and to reduce mortality in severe cases.
Parallel Adaptation to Spatially Distinct Distortions
2020-11-20

Optical distortions as a visual disturbance are inherent in many optical devices such as spectacles or virtual reality headsets. In such devices, distortions vary spatially across the visual field. In progressive addition lenses, for example, the left and right regions of the lens skew the peripheral parts of the wearers visual field in opposing directions. The human visual system adapts to homogeneous distortions and the respective aftereffects are transferred to non-retinotopic locations. This study investigates simultaneous adaptation to two opposing distortions at different retinotopic locations. Two oppositely skewed natural image sequences were presented to 10 subjects as adaptation stimuli at two distinct locations in the visual field. To do so, subjects were instructed to keep fixation on a target. Eye tracking was used for gaze control. Change of perceived motion direction was measured in a direction identification task. The point of subjective equality (PSE), that is, the angle at which a group of coherently moving dots was perceived as moving horizontal, was determined for both retinal locations. The shift of perceived motion direction was evaluated by comparing PSE before and after adaptation. A significant shift at both retinal locations in the direction of the skew distortion of the corresponding adaptation stimulus is demonstrated. Consequently, parallel adaptation to two opposing distortions in a retinotopic reference frame was confirmed by this study.
The wizard and the computer: An introduction to preprocessing corpora using R
2020-11-20

The present text adresses readers without any programming skills or experience. It shows in (hopefully) comprehensible and short steps how to use the programming language R. The main focus of this text is to introduce basic functions as well as basic knowledge how to perform your programming task which you will need to preprocess corpora. Later in the text I also introduce how to simulate learning using an error-driven learning rule.
Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study
2020-11-21

The variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochemical method within real-world scenarios such as clinical diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a 'primary' setup and the test data are generated on 'replicate' setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin experiment investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technology) action Raman4clinics. The experiment was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fibre-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-laboratory studies.
Improved protection of outdoor workers from solar ultraviolet radiation: position statement
2020-11-21

Abstract The vast majority of non‐melanoma skin cancer (NMSC) is attributable to excessive exposure to ultraviolet radiation (UVR). Outdoor workers are exposed to an UVR dose at least 2 to 3 times higher than indoor workers and often to daily UVR doses 5 times above internationally recommended limits. The risk of UVR workplace exposure is vastly neglected, and the evident future challenges presented in this statement are contrasted with the current situation regarding legal recognition, patient care and compensation. While prevention is crucial to reduce cancer risks for outdoor workers, it is as much of relevance to better protect them through legally binding rules and regulations. Specific actions are outlined in five recommendations based on a Call to Action (table 1). The role of health professionals, including dermatologists, in this context is crucial.
Baiting/Luring Improves Detection Probability and Species Identification—A Case Study of Mustelids with Camera Traps
2020-11-22

Motion-triggered trail cameras (hereafter camera traps) are powerful tools which are increasingly used in biological research, especially for species inventories or the estimation of species activity. However, camera traps do not always reliably detect animal visits, as a target species might be too fast, too small, or too far away to trigger an image. Therefore, researchers often apply attractants, such as food or glandular scents, to increase the likelihood of capturing animals. Moreover, with attractants, individuals might remain in front of a camera trap for longer periods leading to a higher number of images and enhanced image quality, which in turn might aid in species identification. The current study compared how two commonly used attractants, bait (tuna) and glandular scent (mustelid mix), affected the detection and the number of images taken by camera traps compared to control camera sites with conventional camera traps. We used a before–after control group design, including a baseline. Attractants increased the probability of detecting the target species and number of images. Tuna experiments produced on average 7.25 times as many images per visit than control camera traps, and scent lures produced on average 18.7 times as many images per visit than the control traps.
Arabidopsiscell surface LRR immune receptor signaling through the EDS1-PAD4-ADR1 node
2020-11-23

Abstract Plants use both cell surface and intracellular immune receptors with leucine rich-repeat (LRRs) to detect pathogens. LRR receptor kinases (LRR-RKs) and LRR receptor-like proteins (LRR-RPs) recognize extracellular microbe-derived molecules to confer pattern-triggered immunity (PTI), while nucleotide-binding LRR (NLR) proteins detect microbial effectors inside the cell to confer effector-triggered immunity (ETI). Despite PTI and ETI signaling being initiated in different compartments, both rely on the transcriptional activation of similar sets of genes, suggesting convergence in signaling upstream of nuclear events. Here we report that two sets of molecules, helper NLRs from the ADR1 (ACTIVATED DISEASE RESISTANCE 1) family as well as lipase-like proteins EDS1 (ENHANCED DISEASE SUSCEPTIBILITY 1) and PAD4 (PHYTOALEXIN DEFICIENT 4), are required not only for ETI, but also for PTI. A further similarity is seen in the evolutionary patterns of some PTI and ETI receptor genes, with both often being highly polymorphic, and with nevertheless distinct roles of LRR-RK and LRR-RP receptors in immunity. We find that the LRR-RK SOBIR1 directly links LRR-RPs with the ADR1 helper NLR as well as EDS1 and PAD4, suggesting the formation of constitutive supramolecular signalosome complexes at the inner side of the plasma membrane. We propose that the EDS1-PAD4-ADR1 node is an essential component and convergence point for immune signaling cascades activated by both surface-resident LRR-RP receptors and intracellular NLR receptors.
Selected Rhizosphere Bacteria Help Tomato Plants Cope with Combined Phosphorus and Salt Stresses
2020-11-23

Plants are often challenged by multiple abiotic stresses simultaneously. The inoculation of beneficial bacteria is known to enhance plant growth under these stresses, such as phosphorus starvation or salt stress. Here, for the first time, we assessed the efficiency of selected beneficial bacterial strains in improving tomato plant growth to better cope with double stresses in salty and P-deficient soil conditions. Six strains of Arthrobacter and Bacillus with different reservoirs of plant growth-promoting traits were tested in vitro for their abilities to tolerate 2–16% (w/v) NaCl concentrations, and shown to retain their motility and phosphate-solubilizing capacity under salt stress conditions. Whether these selected bacteria promote tomato plant growth under combined P and salt stresses was investigated in greenhouse experiments. Bacterial isolates from Cameroonian soils mobilized P from different phosphate sources in shaking culture under both non-saline and saline conditions. They also enhanced plant growth in P-deficient and salt-affected soils by 47–115%, and their PGP effect was even increased in higher salt stress conditions. The results provide valuable information for prospective production of effective bio-fertilizers based on the combined application of local rock phosphate and halotolerant phosphate-solubilizing bacteria. This constitutes a promising strategy to improve plant growth in P-deficient and salt-affected soils.