julilili42/papers huggingface dataset:
Reduced alpha diversity of the oral microbiome correlates with short progression‐free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib‐based therapy (AGMT MM 1, phase II trial)
2020-11-08

Abstract Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib‐thalidomide‐dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression‐free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (&gt;75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease ( P &lt; .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.
Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers
2020-11-08

Abstract The health impact of prolonged space flight on the human body is not well understood. Liquid biopsies based on cell-free DNA (cfDNA) or exosome analysis provide a noninvasive approach to monitor the dynamics of genomic, epigenomic and proteomic biomarkers, and the occurrence of DNA damage, physiological stress, and immune responses. To study the molecular consequences of spaceflight we profiled cfDNA isolated from plasma of an astronaut (TW) during a year-long mission on the International Space Station (ISS), sampling before, during, and after spaceflight, and compared the results to cfDNA profiling of the subject’s identical twin (HR) who remained on Earth, as well as healthy donors. We characterized cfDNA concentration and fragment size, and the positioning of nucleosomes on cfDNA, observing a significant increase in the proportion of cell-free mitochondrial DNA inflight, suggesting that cf-mtDNA is a potential biomarker for space flight-associated stress, and that this result was robust to ambient transit from the International Space Station (ISS). Analysis of exosomes isolated from post-flight plasma revealed a 30-fold increase in circulating exosomes and distinct exosomal protein cargo, including brain-derived peptides, in TW compared to HR and all known controls. This study provides the first longitudinal analysis of astronaut cfDNA during spaceflight, as well as the first exosome profiles, and highlights cf-mtDNA levels as a potential biomarker for physiological stress or immune system responses related to microgravity, radiation exposure, and other unique environmental conditions on the ISS.
De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy
2020-11-09

Abstract Claudin-11, a tight junction protein, is indispensable in the formation of the radial component of myelin. Here, we report de novo stop-loss variants in the gene encoding claudin-11, CLDN11, in three unrelated individuals presenting with an early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia. Brain MRI showed a myelin deficit with a discrepancy between T1-weighted and T2-weighted images and some progress in myelination especially involving the central and peripheral white matter. Exome sequencing identified heterozygous stop-loss variants c.622T&amp;gt;C, p.(*208Glnext*39) in two individuals and c.622T&amp;gt;G, p.(*208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T&amp;gt;C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein. Extended claudin-11 is predicted to form an alpha helix not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins. Our observations suggest that stop-loss variants in CLDN11 expand the genetically heterogeneous spectrum of hypomyelinating leukodystrophies.
In vitro investigation of an intracranial flow diverter with a fibrin-based, hemostasis mimicking, nanocoating
2020-11-09

Abstract Flow diversion aims at treatment of intracranial aneurysms via vessel remodeling mechanisms, avoiding the implantation of foreign materials into the aneurysm sack. However, complex implantation procedure, high metal surface and hemodynamic disturbance still pose a risk for thromboembolic complications in the clinical praxis. A novel fibrin and heparin based nano coating considered as a hemocompatible scaffold for neointimal formation was investigated regarding thrombogenicity and endothelialization. The fibrin-heparin coating was compared to a bare metal as well as fibrin- or heparin-coated flow diverters. The implants were tested separately in regard to inflammation and coagulation markers in two different in vitro hemocompatibility models conducted with human whole blood ( n = 5). Endothelialization was investigated through a novel dynamic in vitro cell seeding model containing primary human cells with subsequent viability assay. It was demonstrated that platelet loss and platelet activation triggered by presence of a bare metal stent could be significantly reduced by applying the fibrin-heparin, fibrin and heparin coating. Viability of endothelial cells after proliferation was similar in fibrin-heparin compared to bare metal implants, with a slight, non-significant improvement observed in the fibrin-heparin group. The results suggest that the presented nanocoating has the potential to reduce thromboembolic complications in a clinical setting. Though the new model allowed for endothelial cell proliferation under flow conditions, a higher number of samples is required to assess a possible effect of the coating.
Spatial Anisotropy of Charge Transfer at Perfluoropentacene–Pentacene (001) Single-Crystal Interfaces and its Relevance for Thin Film Devices
2020-11-09

Archetypal donor-acceptor (D-A) interfaces composed of perfluoropentacene (PFP) and pentacene (PEN) are examined for charge transfer (CT) state formation and energetics as a function of their respective molecular configuration. To exclude morphological interference, our structural as well as highly sensitive differential reflectance spectroscopy studies were carried out on PFP thin films epitaxially grown on PEN(001) single-crystal facets. Whereas the experimental data supported by complementary theoretical calculations confirm the formation of a strong CT state in the case of a cofacial PFP-PEN stacking, CT formation is energetically less favorable and thus absent for the corresponding head-to-tail configuration as disclosed for the first time. In view of technological implementations, the knowledge gained on the single-crystal references is transferred to thin-film diodes composed of either stacked PFP/PEN bilayers or mixed PFP:PEN heterojunction interfaces. As demonstrated, their electronic and electroluminescent behavior can be consistently described by the absence or presence of interfacial CT states. Thus, our results hint at the thorough design of D-A interfaces to achieve the highest device performances.
In-Hospital Mortality and Complication Rates According to Health Insurance Data in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies in Germany
2020-11-09

Abstract Background Morbidity and in-hospital mortality rates of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany are not known. Methods From 2009 to 2018 all patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRG). The “failure to rescue” (FTR) index, characterizing patients who died after severe but potentially manageable complications, was calculated. Results In total, 8463 patients were included and analyzed. Female sex predominated (1.5:1). Colonic origin of peritoneal metastasis was highest throughout all years, reaching its highest level in 2017 (55%; n = 563) and its lowest level in 2012 (40%; n = 349). Median length of hospital stay reached its maximum in 2017 at 23.9 days and its minimum in 2010 at 22.0 days. Analysis of the total FTR index showed a noticeable improvement over the years, reaching its lowest values in 2017 (9.8%) and 2018 (8.8%). The FTR index for sepsis, peritonitis, and pulmonary complications significantly improved over time. Of the 8463 included patients, 290 died during hospital stay, reflecting an in-hospital mortality rate of 3.4%. Conclusion In-hospital mortality after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is reasonably low compared with other surgical procedures. The improvement in the FTR index reflects efforts to centralize treatment at specialized high-volume centers.
Testing the Keplerian disk hypothesis using x-ray reflection spectroscopy
2020-11-09

The Novikov-Thorne model is the standard framework for the description of\\ngeometrically thin and optically thick accretion disks around black holes and\\nis widely used to study the electromagnetic spectra of accreting black holes.\\nOne of the assumptions of the model is that the particles of the gas move on\\nnearly-geodesic circular orbits on the equatorial plane. In this work, we\\npropose to test the Keplerian velocity of the particles in the accretion disk\\nusing X-ray reflection spectroscopy. We present a modified version of RELXILL\\nin which we introduce a phenomenological parameter, , to quantify\\npossible deviations from Keplerian motion. We use our model to fit a Suzaku\\nobservation of the black hole binary GRS 1915+105. We find that the estimate of\\n is correlated to that of the inclination angle of the disk, , and\\nthat we could test the Keplerian disk hypothesis in the presence of a robust\\nand independent measurement of .\\n
Cytokeratin expression in plasmablastic lymphoma – a possible diagnostic pitfall in the routine work‐up of tumours
2020-11-09

Aims Plasmablastic lymphoma (PBL) is a rare aggressive B‐cell lymphoma that frequently arises at extranodal sites in the setting of immunosuppression. The diagnosis of PBL is complex, owing to a frequent solid or cohesive growth pattern, and an often unusual immunophenotype. Several case reports have described cytokeratin (CK) expression in PBL, introducing a diagnostic pitfall. The aim of this study was to determine the frequency of CK expression in PBL in the largest series available to date. Methods and results By using immunohistochemistry in a cohort of 72 PBLs, we identified CK8/18 positivity in 11 of 72 cases (15%) and AE1/3 positivity in six of 65 cases (9%), clearly contrasting with a control series of non‐PBL aggressive B‐cell lymphomas (one of 96 diffuse large B‐cell lymphomas), as well as with data in the literature describing only occasional CK expression in haematological neoplasms. Conclusions Our data indicate CK expression in a substantial number (15%) of PBLs. In view of the particular morphological features of PBL and its frequent negativity for the common leukocyte antigen and B‐cell markers, this feature represents a pitfall in the routine diagnostic work‐up of PBL, and requires more extensive immunohistochemical and molecular characterisation of cases entering the differential diagnosis.
Plutarch’s Platonic Question IX: The Trichonomy of the Soul from the Perspective of Music Theory (Politeia 443d-e)
2020-11-09

In the IXth question of his Platonicae Quaestiones, Plutarch takes up the musical analogy of Politeia 443d-e, which applies the trichonomy of the soul to the concept of harmony by means of the three horoi. The concrete question of whether Plato assigned the place of mese to spirit or to reason is left open by Plutarch according to his zétema concept, but offers meaningful opportunities for the understanding of Platonic soul trichonomy: both the peculiarity of the horoi and the ambiguity of harmonia must be diligently assessed from a musictheoretical perspective in order to comprehensively understand the analogy of soul trichonomy.
Nano zinc elicited biochemical characterization, nutritional assessment, antioxidant enzymes and fatty acid profiling of rapeseed
2020-11-10

The use of nanomaterials in agriculture is a current need and could be helpful in overcoming food security risks. Brassica napus L. is the third most important crop for edible oil, having double low unsaturated fatty acids. In the present study, we investigated the effects of green synthesized Zn NPs on biochemical effects, antioxidant enzymes, nutritional quality parameters and on the fatty acid profile of rapeseed ( B . napus ). Plant-mediated synthesis of zinc nanoparticles (Zn NPs) was carried out using Mentha arvensis L. leaf extract followed by characterization through ultraviolet–visible spectroscopy (UV-vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-Ray (EDX), and X-Ray diffraction (XRD). NPs exhibited irregular shapes ranging in size from 30–70 nm and EDX analysis confirmed 96.08% of Zn in the sample. The investigated biochemical characterization (protein content, proline content, total soluble sugar (TSS), total flavonoid content (TFC), and total phenolic content (TPC) showed a substantial change on exposure to Zn NPs. A dose-dependent gradual increase was observed in the antioxidant enzymes, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Oil and moisture contents dropped significantly from the control level in the rapeseed ( B . napus ) varieties. However, different trends in nutritional (Zn, Na+, K+) and fatty acid profiling of B . napus have been noted. This study demonstrates that Zn NPs have the potential to improve the biochemical, nutritional, antioxidant enzymes, and fatty acid profile of B . napus varieties.
Aberrant COL11A1 splicing causes prelingual autosomal dominant nonsyndromic hearing loss in the DFNA37 locus
2020-11-10

Alpha-chain collagen molecules encoded by genes that include COL11A1 are essential for skeletal, ocular, and auditory function. COL11A1 variants have been reported in syndromes involving these organ systems. However, a description of the complete clinical spectrum is lacking, as evidenced by a recent association of autosomal dominant nonsyndromic hearing loss due to a splice-altering variant in COL11A1, mapping the DFNA37 locus. Here, we describe two German families presenting prelingual autosomal dominant nonsyndromic hearing loss with novel COL11A1 heterozygous splice-altering variants (c.652-1G>C and c.4338+2T>C) that were molecularly characterized. Interestingly, the c.652-1G>C variant affects the same intron 4 canonical splice site originally reported in the DFNA37 family (c.652-2A>C) but elicits a different splicing outcome. Furthermore, the c.4338+2T>C variant originated de novo. We provide clinical and molecular genetic evidence to unambiguously confirm that COL11A1 splice-altering variants cause DFNA37 hearing loss and affirm that COL11A1 be included in the genetic testing of patients with nonsyndromic deafness.
The Antarium: A Reconstructed Visual Reality Device for Ant Navigation Research
2020-11-10

We constructed a large projection device (the Antarium) with 20,000 UV-Blue-Green LEDs that allows us to present tethered ants with views of their natural foraging environment. The ants walk on an air-cushioned trackball, their movements are registered and can be fed back to the visual panorama. Views are generated in a 3D model of the ants' environment so that they experience the changing visual world in the same way as they do when foraging naturally. The Antarium is a biscribed pentakis dodecahedron with 55 facets of identical isosceles triangles. The length of the base of the triangles is 368 mm resulting in a device that is roughly 1 m in diameter. Each triangle contains 361 blue/green LEDs and nine UV LEDs. The 55 triangles of the Antarium have 19,855 Green and Blue pixels and 495 UV pixels, covering 360° azimuth and elevation from -50° below the horizon to +90° above the horizon. The angular resolution is 1.5° for Green and Blue LEDs and 6.7° for UV LEDs, offering 65,536 intensity levels at a flicker frequency of more than 9,000 Hz and a framerate of 190 fps. Also, the direction and degree of polarisation of the UV LEDs can be adjusted through polarisers mounted on the axles of rotary actuators. We build 3D models of the natural foraging environment of ants using purely camera-based methods. We reconstruct panoramic scenes at any point within these models, by projecting panoramic images onto six virtual cameras which capture a cube-map of images to be projected by the LEDs of the Antarium. The Antarium is a unique instrument to investigate visual navigation in ants. In an open loop, it allows us to provide ants with familiar and unfamiliar views, with completely featureless visual scenes, or with scenes that are altered in spatial or spectral composition. In closed-loop, we can study the behavior of ants that are virtually displaced within their natural foraging environment. In the future, the Antarium can also be used to investigate the dynamics of navigational guidance and the neurophysiological basis of ant navigation in natural visual environments.
Split-based points from the Swabian Jura highlight Aurignacian regional signatures
2020-11-10

The systematic use of antlers and other osseous materials by modern humans marks a set of cultural and technological innovations in the early Upper Paleolithic, as is seen most clearly in the Aurignacian. Split-based points, which are one of the most common osseous tools, are present throughout most regions where the Aurignacian is documented. Using results from recent and ongoing excavations at Geißenklösterle, Hohle Fels and Vogelherd, we nearly tripled the sample of split-based points from 31 to 87 specimens, and thereby enhance our understanding of the technological economy surrounding the production of osseous tools. Aurignacian people of the Swabian Jura typically left spit-based points at sites that appear to be base camps rich with numerous examples of personal ornaments, figurative art, symbolic imagery, and musical instruments. The artifact assemblages from SW Germany highlight a production sequence that resembles that of SW France and Cantabria, except for the absence of tongued pieces. Our study documents the life histories of osseous tools and demonstrates templates for manufacture, use, recycling, and discard of these archetypal artifacts from the Aurignacian. The study also underlines the diversified repertoire of modern humans in cultural and technological realms highlighting their adaptive capabilities.
Changes in Halogen (F, Cl, Br, and I) and S Ratios in Rock-Forming Minerals as Monitors for Magmatic Differentiation, Volatile-Loss, and Hydrothermal Overprint: The Case for Peralkaline Systems
2020-11-10

We determined the halogen (F, Cl, Br, and I) and sulfur (S) concentrations in Cl-rich rock-forming minerals from five peralkaline complexes. We investigated sodalite (N = 42), eudialyte-group minerals (N = 84), and tugtupite (N = 8) from representative rock samples derived from Ilímaussaq (South Greenland), Norra Kärr (Sweden), Tamazeght (Morocco), Lovozero, and Khibina (Russian Federation). Taken together, sodalite and eudialyte-group minerals dominate the Cl and Br budget of the investigated rocks. For F, however, several other phases (e.g., amphibole, fluorite, villiaumite, and minerals of the rinkite group and the apatite supergroup) are additional sinks, and parts of the S may be scavenged in generally rare sulfides. The investigated minerals contain Cl at the wt.% level, F and S concentrations are in the hundreds to thousands of μg/g-range, Br is less common (0.2–200 μg/g) and I is rare (mostly well below 1 μg/g). Normalized to Cl, sodalite prefers Br relative to eudialyte-group minerals, while F is always enriched in the latter. Our data show that both F and S may represent important components in eudialyte-group minerals, sometimes at similar levels as Cl, which normally dominates. Sulfur reveals redox-dependent behavior: Under reduced crystallization conditions, S is more compatible in eudialyte-group minerals (EGM) than in sodalite, which flips to the opposite under water-rich and presumably more oxidized conditions. We investigate the applicability of F/Cl, Br/Cl, and S/Cl ratios in these minerals in peralkaline systems to better understand the interplay of magmatic differentiation, fluid loss and hydrothermal overprint. Similar to apatite in metaluminous systems, fractionation of sodalite, and eudialyte-group minerals in peralkaline magmas leads to decreasing Br/Cl ratios. The data presented in this study bear implications for the mineral chemistry and compositional variation of sodalite and especially EGM in general. Volatile components in EGM that are not normally considered, such as F and S, can reach concentrations of thousands of μg/g. Especially in the case of F, with its low atomic weight, the results obtained in this study indicate that it is very significant for formulae calculations, neutral charge-balance, and similar aspects at such concentration levels. This study demonstrates that halogen contents and ratios are sensitive monitors for a variety of processes in magmatic-hydrothermal systems, including magmatic fractionation, volatile loss, and fluid–rock interaction.
In situ detection of protein interactions for recombinant therapeutic enzymes
2020-11-10

Abstract Despite their therapeutic potential, many protein drugs remain inaccessible to patients since they are difficult to secrete. Each recombinant protein has unique physicochemical properties and requires different machinery for proper folding, assembly, and posttranslational modifications (PTMs). Here we aimed to identify the machinery supporting recombinant protein secretion by measuring the protein–protein interaction (PPI) networks of four different recombinant proteins (SERPINA1, SERPINC1, SERPING1, and SeAP) with various PTMs and structural motifs using the proximity‐dependent biotin identification (BioID) method. We identified PPIs associated with specific features of the secreted proteins using a Bayesian statistical model and found proteins involved in protein folding, disulfide bond formation, and N‐glycosylation were positively correlated with the corresponding features of the four model proteins. Among others, oxidative folding enzymes showed the strongest association with disulfide bond formation, supporting their critical roles in proper folding and maintaining the ER stability. Knockdown of disulfide‐isomerase PDIA4 , a measured interactor with significance for SERPINC1 but not SERPINA1, led to the decreased secretion of SERPINC1, which relies on its extensive disulfide bonds, compared to SERPINA1, which has no disulfide bonds. Proximity‐dependent labeling successfully identified the transient interactions supporting synthesis of secreted recombinant proteins and refined our understanding of key molecular mechanisms of the secretory pathway during recombinant protein production.