julilili42/papers huggingface dataset:
Response of inflammatory cytokines to acute bout of exercise and 8-week intervention study in untrained subjects with obesity
2022-05-01

Background Acute physical exercise leads to rapid changes in blood cytokines. However, the changes are variable and can be influenced by reduced physical fitness and other type 2 diabetes risk factors. We investigated the influence of metabolic parameters and endurance training on the acute release of cytokines in subjects at high risk to develop type 2 diabetes.
Identification of functional defects promoting leukemogenesis in GATA2-deficient individuals
2022-05-01

Hematopoiesis is the process in which blood cells are produced by the proliferation of hematopoietic stem and progenitor cells (HSPCs) and their differentiation into the various blood cell subsets. This process is tightly regulated by different co- and transcription factors. Amongst them, GATA2 plays a pivotal role in the proliferation and balance of hematopoietic stem cells (HSCs). Thus, germline GATA2 mutations can disrupt hematopoiesis leading to cytopenia, immunodeficiency or myeloid neoplasia, for instance myelodysplastic syndrome (MDS) or leukemia. Using transgenic mice who are heterozygous in GATA2 (Gata2+/-) in the hematopoietic system, we have previously demonstrated that bone marrow (BM) failure and secondary leukemia can be induced by transplanting Gata2+/- HSPCs into lethally irradiated mice. Interestingly, two weeks after transplantation, HSPC numbers are significantly reduced in the BM of mice who were transplanted with Gata2+/- HSPCs. At later time points, Gata2+/- HSPCs reconstitute the BM of recipients before reaching exhaustion. We now investigate whether, after transplantation, Gata2+/- HSPC numbers decrease due to increased apoptosis or reduced proliferation.
Ketamine Metabolite Plasma Levels as Potential Blood Markers of Ketamine Efficacy in Treatment Resistant Depression
2022-05-01

Introduction Accumulating evidence has revealed robust fast-acting antidepressant effects of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, in patients with treatment-resistant depression (TRD). However, considering that clinical responses can only be observed in 50% of TRD patients [1], treatment decisions lack predictors on patients' individual benefit.
Is it Time to Reevaluate the Therapeutic Reference Range for the Antidepressant Drug Venlafaxine?
2022-05-01

Introduction Current guidelines recommend Therapeutic Drug Monitoring (TDM) of venlafaxine (VEN) for dose titration within 100-400 ng/mL, referring to the active moiety (VEN+O-desmethylvenlafaxine; ODV). A therapeutic reference range bases upon a sound concentration efficacy relationship, which has not been systematically verified for VEN/ODV yet.
Verschwörungstheorien zu 9/11
2022-05-01

Abstract This article discusses 9/11 conspiracy theories with a focus on the United States and Europe. After defining conspiracy theories – and thus distinguishing conspiracy theories about the attacks of September 11, 2001, from the official version, which also revolves around a conspiracy – the article traces the emergence of these theories and their development over the twenty years since the attacks. As I show, 9/11 conspiracy theories emerged quickly after the events. However, for two years they were far more popular in Germany and France where they were fueled by anti-Americanism than in the United States where they only gained traction with the invasion of Iraq in 2003. Their popularity peaked around 2005 with the release of the Loose Change films online, but they never went out of fashion entirely. As is typical of conspiracy theories revolving around specific events, they were over time integrated in larger conspiracist narratives such as that of the “Great Replacement.” People who believe in 9/11 conspiracy theories – just as those who believe in others – should not be dismissed as mentally ill, as their beliefs can be symptoms of real anxieties and grievances.
Sleep, Pain, and Neurodegeneration: A Mendelian Randomization Study
2022-05-02

Our aim was to determine whether the genetic liability to sleep and pain-related traits have a causal effect on risk of neurodegeneration in individuals of predominantly European ancestry. We selected five neurodegenerative disorders, namely, age-related macular degeneration (AMD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson's disease (PD). Sleep duration (SD), short sleep (SS), long sleep (LS), chronotype (CHR), morning person (MP), insomnia (INS), and multisite chronic pain (MCP) were considered as exposures. We conducted Mendelian randomization (MR) using an inverse-variance weighted (IVW) method to compute causal effect estimates using latest available GWAS data sets. The MP phenotype was observed as the strongest risk factor for genetic liability to AMD (OR IVW = 1.192; 95% CI 1.078, 1.318, P = 0.0007). We observed suggestive evidence of risky effects of CHR on AMD ( P = 0.0034), SS on AD ( P = 0.0044), and INS on ALS ( P = 0.0123). However, we failed to observe any role of pain. The results were robust on sensitivity analyses. Our study highlighted the role of MP as a risk factor for AMD.
Salinity Impact on Composition and Activity of Nitrate-Reducing Fe(II)-Oxidizing Microorganisms in Saline Lakes
2022-05-02

NRFeOx microorganisms are globally distributed in various types of environments and play a vital role in iron transformation and nitrate and heavy metal removal. However, most known NRFeOx microorganisms were isolated from freshwater and marine environments, while their identity and activity under hypersaline conditions remain unknown.
Chromoendoscopy in Combination with Random Biopsies for Patients with Pathogenic CDH1 Mutations Undergoing Endoscopic Surveillance
2022-05-02

Abstract Objectives Germline mutations in the CDH1 -gene are identified as the cause of 30–40% of cases of hereditary diffuse gastric cancer, an autosomal-dominant inherited cancer predisposition syndrome. Given this high risk of developing diffuse gastric cancer, carriers of a pathogenic CDH1 germline mutation are advised to undergo prophylactic gastrectomy. For patients preferring conservative management, endoscopic surveillance is recommended. The detection of diffuse gastric cancer using white light endoscopy, however, remains challenging. Methods Patients with pathogenic CDH1 mutation underwent (chromo)endoscopic surveillance or endoscopy prior to surgery. Biopsies were taken at suspicious sites identified by chromoendoscopy. In addition, endoscopically normal areas were assessed with mapping biopsies. Detection rates from endoscopic biopsies (mapping vs. targeted) and gastrectomy specimen were then compared. Result Between 11/2015 and 12/2020, ten patients from four families with a known CDH1 germline mutation had a total of n = 24 endoscopies with n = 518 total biopsies being examined. Three patients were diagnosed with GC during the study period. These patients all had suspicious chromoendoscopic lesions (= detection rate 100%). In two of three patients who had suspicious chromoendoscopic lesions, signet cell carcinoma was also detected in mapping biopsies and multiple additional cancer foci were identified in the gastrectomy specimen. Conclusion Chromoendoscopy facilitated detection of gastric carcinoma foci in CDH1 mutation carriers. Chromoendoscopy identified all patients with gastric cancer, but not all cancer foci present in these patients. We conclude that for patients opting against prophylactic total gastrectomy, the addition of chromoendoscopy to white light could be used to enhance diagnostic reliability of endoscopic surveillance.
CORK1, a LRR-Malectin Receptor Kinase for Cellooligomer Perception in Arabidopsis thaliana
2022-05-02

Abstract Cell wall integrity (CWI) maintenance is central for plant cells. Mechanical or chemical distortions, pH changes, or breakdown products of cell wall polysaccharides activate plasma membrane-localized receptors and induce appropriate downstream responses. Microbial interactions alter or destroy the structure of the plant cell wall, connecting CWI maintenance to immune responses. Cellulose is the major polysaccharide in the primary and secondary cell wall. Its breakdown generates short-chain cellooligomers which induce Ca 2+ -dependent CWI responses. We have shown here that these responses require the malectin domain-containing CELLOOLIGOMER-RECEPTOR KINASE 1 (CORK1) in Arabidopsis . CORK1 is required for cellooligomer-induced cytoplasmic Ca 2+ elevation, reactive oxygen species (ROS) production, mitogen associated protein kinase (MAPK) activation, cellulose synthase phosphorylation, and the regulation of CWI-related genes including those involved in biosynthesis of cell wall material, secondary metabolites and tryptophan. Phosphoproteome analyses identified early targets involved in signaling, cellulose synthesis, the endoplasmatic reticulum/Golgi secretory pathway, cell wall repair and immune responses. Two conserved phenylalanine residues in the malectin domain are crucial for CORK1 function. We propose that cellulose breakdown products bind to the malectin domain in CORK1, indicating its role as a novel receptor kinase for CWI maintenance.
Multi-methodological Characterisation of Medieval to Early Modern Coral Beads from a Cesspit of the “Fronerei auf dem Schrangen” in Lübeck (Germany)
2022-05-02

Eight late medieval to early modern red beads representative of a total of 41 from a cesspit of the “Fronerei auf dem Schrangen” in Lübeck, Germany, were investigated using micro X-ray computed tomography (3D-μXCT), X-ray microdiffraction (μ-XRD2), transmission electron microscopy (HRTEM) and Raman spectroscopy (RS). The microscopic properties of the material were characterised non- destructively or minimally invasively for colouration, mineralogical and chemical composition determination but also with regard to their macroscopic external appearance. The polished beads are spherical with flattered tops and boreholes perpendicular to the flattening and show partially traces of working. As base material for all examined beads, high Mg-Calcite with polyenes could be identified. Combined with density and microstructure data, the beads are undoubtedly red precious corals, identical with modern corallium rubrum from the Mediterranean also confirmed by C- and O-isotopic analyses. The studies provide general criteria for the determination of corallium rubrum, confirming the macroscopically determined identification of other coral artefacts associated with the Hanseatic League, and thus prove their iconographic importance as well as the trade contacts with the Mediterranean region. However, the extent to which the characteristics of the coral beads indicate accidental or intentional individual or collective societal or social circumstances is left to further study.
Research compendium for 'The contribution of integrated 3D model analysis to Protoaurignacian stone tool design'
2022-05-02

Abstract: Protoaurignacian foragers relied heavily on the production and use of bladelets. Techno-typological studies of these implements have provided insights into important aspects of cultural variability. However, new technologies have seldom been used to quantify patterns of stone tool design. Taking advantage of a new scanning protocol and open-source software, we conduct the first 3D analysis of a Protoaurignacian assemblage, focusing on the selection and modification of blades and bladelets. We study a large sample of complete blanks and retouched tools from the early Protoaurignacian assemblage at Fumane Cave in northeastern Italy. Our main goal is to validate and refine previous techno-typological considerations employing a 3D geometric morphometrics approach complemented by 2D analysis of cross-section outlines and computations of retouch angle. The encouraging results show the merits of the proposed integrated approach and confirm that bladelets were the main focus of stone knapping at the site. Among modified bladelets, various retouching techniques were applied to achieve specific shape objectives. We suggest that the variability observed among retouched bladelets relates to the design of multi-part artifacts that need to be further explored via renewed experimental and functional studies. Overview of contents: 01. AGMT3-D project of the first dataset used in the study; 02. AGMT3-D project of the second dataset used in the study; 03. Raw outline data of the middle cross-section. Each specimens has a dedicate .txt file; 04. Raw outline data of the upper cross-section. Each specimens has a dedicate .txt file; 05. Angles3-D project with all files generated by the software (.mat and .xlsx formats) to quantify the mean retouch angle of retouched bladelets; 06. R project and scripts for the 1) 2D shape analysis of the middle and upper cross-sections of retouched bladelets and the 2) design of all bivariate plots and boxplots with jittered points used in the paper. All related datasets, principal components, and generated figures are included in the folder; 07. Folder with all figures published in the paper and in its supplementary materials; 08. Dataset of the first study in .csv with all attributes used to run the statistical analysis presented in the paper; 09. Dataset of the second study in .csv with all attributes used to run the statistical analysis presented in the paper; 10. Dataset for the study of the upper cross-sections in .csv with all attributes used to run the statistical analysis presented in the paper; 11. Dataset for the study of the middle cross-sections in .csv with all attributes used to run the statistical analysis presented in the paper; 12. Dataset in .csv used to study the mean retouch angles; 13. Supplementary information file in .pdf with all supplementary figures and tables. Extra: All 3D meshes of blades and bladelets are available on Zenodo following this link: https://doi.org/10.5281/zenodo.6362150.
Correlates of individual voice and face preferential responses during resting state
2022-05-03

Abstract Human nonverbal social signals are transmitted to a large extent by vocal and facial cues. The prominent importance of these cues is reflected in specialized cerebral regions which preferentially respond to these stimuli, e.g. the temporal voice area (TVA) for human voices and the fusiform face area (FFA) for human faces. But it remained up to date unknown whether there are respective specializations during resting state, i.e. in the absence of any cues, and if so, whether these representations share neural substrates across sensory modalities. In the present study, resting state functional connectivity (RSFC) as well as voice- and face-preferential activations were analysed from functional magnetic resonance imaging (fMRI) data sets of 60 healthy individuals. Data analysis comprised seed-based analyses using the TVA and FFA as regions of interest (ROIs) as well as multi voxel pattern analyses (MVPA). Using the face- and voice-preferential responses of the FFA and TVA as regressors, we identified several correlating clusters during resting state spread across frontal, temporal, parietal and occipital regions. Using these regions as seeds, characteristic and distinct network patterns were apparent with a predominantly convergent pattern for the bilateral TVAs whereas a largely divergent pattern was observed for the bilateral FFAs. One region in the anterior medial frontal cortex displayed a maximum of supramodal convergence of informative connectivity patterns reflecting voice- and face-preferential responses of both TVAs and the right FFA, pointing to shared neural resources in supramodal voice and face processing. The association of individual voice- and face-preferential neural activity with resting state connectivity patterns may support the perspective of a network function of the brain beyond an activation of specialized regions.
Extremely low arylsulfatase A enzyme activity does not necessarily cause symptoms: A long‐term follow‐up and review of the literature
2022-05-04

Abstract Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency of arylsulfatase A (ARSA). Heterozygous carriers of disease‐causing variants and individuals harbouring pseudodeficiency alleles in the ARSA gene exhibit reduced ARSA activity. In the context of these genotypes, low ARSA activity has been suggested to lead to an atypical form of MLD or other neurological abnormalities, but data are limited. The aim of our study was to analyse the impact of low ARSA activity in two subjects who are heterozygous for the ARSA pseudodeficiency allele and a disease‐causing variant. Biochemical testing included ARSA activity measurements and urinary sulfatide analysis. Biochemical data of a large cohort of MLD patients, heterozygotes, pseudodeficient individuals and healthy controls were analysed. MRI was performed at 3T using T1‐ and T2‐weighted sequences and MR spectroscopy. We present two long‐term follow‐ups who are heterozygous for the ARSA pseudodeficiency allele and a disease‐causing variant in the ARSA gene in cis. The two related index cases exhibit markedly reduced ARSA activity compared to controls and heterozygous carriers. The neurological evaluation and MRI do not reveal any abnormalities. Our data underline that extremely low enzyme activity due to a pseudodeficiency allele and a disease‐causing variant in the ARSA gene even in cis does not lead to clinical symptoms or pre‐symptomatic MRI changes suspicious for MLD. The review of literature corroborates that any association of low ARSA activity with disease features remains questionable. It seems important to combine the measurement of ARSA activity with elevated sulfatide as well as genetic testing, as done in current newborn screening approaches. Heterozygosity for metachromatic leukodystrophy and an arylsulfatase A pseudodeficiency allele does not cause neurological or neuropsychiatric features.
Blood Eosinophils Are Associated with Efficacy of Targeted Therapy in Patients with Advanced Melanoma
2022-05-04

Background: Eosinophils appear to contribute to the efficacy of immunotherapy and their frequency was suggested as a predictive biomarker. Whether this observation could be transferred to patients treated with targeted therapy remains unknown. Methods: Blood and serum samples of healthy controls and 216 patients with advanced melanoma were prospectively and retrospectively collected. Freshly isolated eosinophils were phenotypically characterized by flow cytometry and co-cultured in vitro with melanoma cells to assess cytotoxicity. Soluble serum markers and peripheral blood counts were used for correlative studies. Results: Eosinophil-mediated cytotoxicity towards melanoma cells, as well as phenotypic characteristics, were similar when comparing healthy donors and patients. However, high relative pre-treatment eosinophil counts were significantly associated with response to MAPKi (p = 0.013). Eosinophil-mediated cytotoxicity towards melanoma cells is dose-dependent and requires proximity of eosinophils and their target in vitro. Treatment with targeted therapy in the presence of eosinophils results in an additive tumoricidal effect. Additionally, melanoma cells affected eosinophil phenotype upon co-culture. Conclusion: High pre-treatment eosinophil counts in advanced melanoma patients were associated with a significantly improved response to MAPKi. Functionally, eosinophils show potent cytotoxicity towards melanoma cells, which can be reinforced by MAPKi. Further studies are needed to unravel the molecular mechanisms of our observations.
Hybrid Chemoenzymatic Synthesis of C7‐Sugars for Molecular Evidence of in vivo Shikimate Pathway Inhibition
2022-05-04

Abstract The design of distinctive chemical synthesis strategies aims for the most efficient routes towards versatile compounds in drug target studies. Here, we establish a powerful hybrid synthetic approach of total chemical and chemoenzymatic synthesis to efficiently obtain various 7‐deoxy‐sedoheptulose (7dSh, 1 ) analogues, unique C 7 sugars, for structure‐activity relationship studies. 7dSh ( 1 ) is a rare microbial sugar with in planta herbicidal activity. As natural antimetabolite of 3‐dehydroquinate synthase (DHQS), 7dSh ( 1 ) inhibits the shikimate pathway, which is essential for the synthesis of aromatic amino acids in bacteria, fungi, and plants, but absent in mammals. As glyphosate, the most used chemical herbicide faces restrictions worldwide, DHQS has gained more attention as valid target of herbicides and antimicrobial agents. In vitro and in vivo analyses of the C 7 ‐deoxysugars confirm DHQS as enzymatic target, highlight the crucial role of uptake for inhibition and add molecular aspects to target mechanism studies of C 7 ‐sugars as our contribution to global efforts for alternative weed‐control strategies.
A scaled-up planetary system around a supernova progenitor
2022-05-05

Context. Virtually all known exoplanets reside around stars with M &lt; 2.3 M ⊙ either due to the rapid evaporation of the protostellar disks or to selection effects impeding detections around more massive stellar hosts. Aims. To clarify if this dearth of planets is real or a selection effect, we launched the planet-hunting B-star Exoplanet Abundance STudy (BEAST) survey targeting B stars (M &gt; 2.4 M ⊙ ) in the young (5−20 Myr) Scorpius-Centaurus association by means of the high-contrast spectro-imager SPHERE at the Very Large Telescope. Methods. In this paper we present the analysis of high-contrast images of the massive (M ~ 9 M ⊙ ) star μ 2 Sco obtained within BEAST. We carefully examined the properties of this star, combining data from Gaia and from the literature, and used state-of-the-art algorithms for the reduction and analysis of our observations. Results. Based on kinematic information, we found that μ 2 Sco is a member of a small group which we label Eastern Lower Scorpius within the Scorpius-Centaurus association. We were thus able to constrain its distance, refining in turn the precision on stellar parameters. Around this star we identify a robustly detected substellar companion (14.4 ± 0.8 M J )at a projected separation of 290 ± 10 au, and a probable second similar object (18.5 ± 1.5 M J ) at 21 ± 1 au. The planet-to-star mass ratios of these objects are similar to that of Jupiter to the Sun, and the flux they receive from the star is similar to those of Jupiter and Mercury, respectively. Conclusions. The robust and the probable companions of μ 2 Sco are naturally added to the giant 10.9 M J planet recently discovered by BEAST around the binary b Cen system. While these objects are slightly more massive than the deuterium burning limit, their properties are similar to those of giant planets around less massive stars and they are better reproduced by assuming that they formed under a planet-like, rather than a star-like scenario. Irrespective of the (needed) confirmation of the inner companion, μ 2 Sco is the first star that would end its life as a supernova that hosts such a system. The tentative high frequency of BEAST discoveries is unexpected, and it shows that systems with giant planets or small-mass brown dwarfs can form around B stars. When putting this finding in the context of core accretion and gravitational instability formation scenarios, we conclude that the current modeling of both mechanisms is not able to produce this kind of companion. The completion of BEAST will pave the way for the first time to an extension of these models to intermediate and massive stars.