julilili42/papers huggingface dataset:
Combined High‐Speed Atomic Force and Optical Microscopy Shows That Viscoelastic Properties of Melanoma Cancer Cells Change during the Cell Cycle
2021-12-22

Abstract Current high‐speed atomic force microscopy (HS‐AFM) setups reach imaging speeds of several images per second but often have limited options for imaging live cells because of a small scan range, a lack of environmental control, or a missing combination with optical phase‐contrast or fluorescence microscopy. A HS‐AFM setup is therefore developed with a large scan range optimized for imaging live cells. The setup is equipped with temperature and CO 2 control and is mounted on an inverted optical microscope providing high‐quality phase‐contrast and fluorescence microscopy. To demonstrate the capabilities of the setup, fast force mapping on live human platelets is performed. Further, HS‐AFM images and optical phase‐contrast and actin fluorescence images of live cancer cells are simultaneously recorded, and two state‐of‐the‐art AFM modes for imaging viscoelastic sample properties, force clamp force mapping and resonance compensating chirp mode, are compared. The setup is then applied to the investigation of viscoelastic material properties of cells in different cell cycle states. Using a melanoma cell line with a fluorescent cell cycle sensor, it is found that during the cell cycle not only cell volume and morphology, but also viscoelastic material properties significantly change, with increasing stiffness and decreasing fluidity from the G1 through the G1/S to the S/G2/M phases.
Gender differences in the labour market entry of STEM graduates
2021-12-22

Many women do not work in science, technology, engineering, and mathematics (STEM) occupations even though they have degrees in these subjects. To shed light on this problem, we use information from the German Graduate Panel and show a significant gender gap among STEM graduates working in degree-related occupations after graduation. Therefore, we focus on university graduates' transition into the labour market and include male and female non-STEM and STEM graduates. We find that male STEM graduates are more likely to work in a degree-related field than other men. A gender gap in degree-related work in STEM occupations shows that this is not the case for women. Separating STEM into engineering and computer science (EngComp) and mathematics and natural sciences (MatNat) shows that EngComp graduates are the main driver of the STEM effects. The estimations remain robust to a comprehensive set of individual background information. Moreover, bearing children before graduation or at the beginning of one's professional career does not explain the lower entry behaviour of female EngComp graduates. Possible channels for why women with an EngComp degree are not as likely as men to start their professional life in an EngComp occupation are discussed.
An integrated device for fast and sensitive immunosuppressant detection
2021-12-22

Abstract The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported. Graphical abstract
DNA Methylation in INA, NHLH2, and THBS4 Is Associated with Metastatic Disease in Renal Cell Carcinoma
2021-12-22

The detection of DNA methylation in primary tumor tissues could be relevant for early stratification of aggressive renal cell carcinomas (RCCs) as a basis for future personalized adjuvant therapy. Methylated TCGA KIRC based candidate CpG loci in INA, NHLH2, and THBS4 that are possibly associated with RCC metastasis were evaluated by pyrosequencing in 154 paired normal adjacent and primary tumor tissues, as well as in 202 metastatic tissues. Statistical analysis was carried out by bivariate logistic regression for group comparisons, log rank survival analysis, and unsupervised and supervised analysis for the classification of tumors. Increased methylation of INA, NHLH2, and THBS4 loci were significantly associated with distant metastasis in primary tumors (p &lt; 0.05), tissue-specific hypermethylation in metastatic (p = 7.88 × 10−8, 5.57 × 10−10, 2.06 × 10−7) and tumor tissues (p = 3.72 × 10−24, 3.17 × 10−13, 1.58 × 10−19), and shortened progression free survival in patients (p = 0.03). Combined use of CpG site-specific methylation permits the discrimination of tissues with metastatic disease and reveals a significant contribution of CpG sites in all genes to the statistical classification model. Thus, metastasis in RCC is significantly associated with methylation alterations in INA, NHLH2, and THBS4 loci, providing independent information for the potential early detection of aggressive renal cancers as a rationale for stratifying patients to adjuvant therapies.
Pilot Malacology Surveys for the Intermediate Hosts of Schistosomiasis in Rural and Semi-Urban Areas of the Moyen-Ogooué Province, Gabon
2021-12-22

The objective of this pilot malacological survey was to identify the snail intermediate hosts for Schistosoma haematobium in endemic rural and semi-urban areas of Gabon. Snails were collected, morphologically identified, and tested for infection by cercarial shedding. Released cercariae were morphologically identified using low-power light microscopy. A total of six species of snails were collected throughout the study area, with Bulinus truncatus, B. forskalii, and Potadoma spp. being the most predominant species collected. Only the Bulinus species were tested for infection by cercarial shedding, of which only B. truncatus shed cercariae. Some B. truncatus shed mammalian schistosome cercariae, while others shed Gymnocephalus cercariae. Our results indicate that B. truncatus appears to be a potential intermediate host of schistosomiasis in Gabon, where cases of S. haematobium, S. guineensis, and S. intercalatum infection are reported. However, it will be important to further understand the species diversity and transmission dynamics of schistosomes.
Angular structure factor of the hexatic-B liquid crystals: bridging theory and experiment
2021-12-22

We found experimentally that angular profiles of the in-plane X-ray scattering in the hexatic-B phase are well approximated by a convolution of the Gaussian and Lorentzian functions. This result is supported by the known theoretical considerations.
News and uncertainty about COVID-19: Survey evidence and short-run economic impact
2021-12-22

A tailor-made survey documents consumer perceptions of the U.S. economy's response to a large shock: the advent of the COVID-19 pandemic. The survey ran at a daily frequency between March 2020 and July 2021. Consumer perceptions regarding output and inflation react rapidly. Uncertainty is pervasive. A business-cycle model calibrated to the consumer views provides an interpretation. The rise in household uncertainty amplifies the pandemic recession by a factor of three. Different perceptions about monetary policy can explain why consumers and professional forecasters agree on the recessionary impact, but have sharply divergent views about inflation.
Seasonal fluctuations of the rusty carbon sink in thawing permafrost peatlands
2021-12-22

In permafrost peatlands, up to 20% of total organic carbon (OC) is bound to reactive iron (Fe) minerals in the active layer overlying intact permafrost, potentially protecting OC from microbial degradation and transformation into greenhouse gases (GHG) such as CO2 and CH4. During the summer, shifts in runoff and soil moisture influence redox conditions and therefore the balance of Fe oxidation and reduction. Whether this “rusty carbon sink” is stable or continuously dissolved by Fe(III) reduction and reformed by Fe(II) oxidation during redox shifts remains unknown. We exposed ferrihydrite (FH)-coated sand in the active layer along a permafrost thaw gradient in Stordalen mire (Abisko, Sweden) over the summer (June to September) to capture changes in redox conditions and quantify formation and dissolution of reactive Fe(III) (oxyhydr)oxides and associated OC. We found that Fe(III) minerals formed under the constantly oxic conditions in palsa soils overlying intact permafrost over the full summer season. In contrast, in fully-thawed fen areas, conditions were continuously anoxic and by late summer 50.4% of the original Fe(III) (oxyhydr)oxides were lost via dissolution while 44.7% and 4.9% of the Fe remained as Fe(III) and Fe(II) on the sand, respectively. Periodic redox shifts (from 0 mV to +300 mV) were observed over the summer season in the partially-thawed bog due to changes in active layer depth, runoff and soil moisture. This resulted in dissolution and loss of 47.5% of initial Fe(III) (oxyhydr)oxides and release of associated OC in early summer when conditions are wetter and more reduced, and new formation of Fe(III) minerals (34.7% gain in comparison to initial Fe) in the late summer under more dry and oxic conditions which again sequestered Fe-bound organic carbon. Our data suggests that the so-called rusty carbon sink is seasonally dynamic in partially-thawed permafrost peatlands, thus likely either promoting or suppressing carbon mineralization and leading to seasonal changes in GHG emissions.
Two-Component Systems of S. aureus: Signaling and Sensing Mechanisms
2021-12-23

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms underlying signal perception. The differences between the sensing of appropriate signals and the transcriptional activation of the TCS system are often not well described, and the signaling mechanisms are only partially understood. Here, we review present insights into which signals are sensed by histidine kinases in S. aureus to promote appropriate gene expression in response to diverse environmental challenges.
Clinical Trials of Oncolytic Viruses in Breast Cancer
2021-12-23

Breast cancer is the second most common kind of cancer worldwide and oncolytic viruses may offer a new treatment approach. There are three different types of oncolytic viruses used in clinical trials; (i) oncolytic viruses with natural anti-neoplastic properties; (ii) oncolytic viruses designed for tumor-selective replication; (iii) oncolytic viruses modified to activate the immune system. Currently, fourteen different oncolytic viruses have been investigated in eighteen published clinical trials. These trials demonstrate that oncolytic viruses are well tolerated and safe for use in patients and display clinical activity. However, these trials mainly studied a small number of patients with different advanced tumors including some with breast cancer. Future trials should focus on breast cancer and investigate optimal routes of administration, occurrence of neutralizing antibodies, viral gene expression, combinations with other antineoplastic therapies, and identify subtypes that are particularly suitable for oncolytic virotherapy.
The Diversity, Metabolomics Profiling, and the Pharmacological Potential of Actinomycetes Isolated from the Estremadura Spur Pockmarks (Portugal)
2021-12-23

The Estremadura Spur pockmarks are a unique and unexplored ecosystem located in the North Atlantic, off the coast of Portugal. A total of 85 marine-derived actinomycetes were isolated and cultured from sediments collected from this ecosystem at a depth of 200 to 350 m. Nine genera, Streptomyces, Micromonospora, Saccharopolyspora, Actinomadura, Actinopolymorpha, Nocardiopsis, Saccharomonospora, Stackebrandtia, and Verrucosispora were identified by 16S rRNA gene sequencing analyses, from which the first two were the most predominant. Non-targeted LC-MS/MS, in combination with molecular networking, revealed high metabolite diversity, including several known metabolites, such as surugamide, antimycin, etamycin, physostigmine, desferrioxamine, ikarugamycin, piericidine, and rakicidin derivatives, as well as numerous unidentified metabolites. Taxonomy was the strongest parameter influencing the metabolite production, highlighting the different biosynthetic potentials of phylogenetically related actinomycetes; the majority of the chemical classes can be used as chemotaxonomic markers, as the metabolite distribution was mostly genera-specific. The EtOAc extracts of the actinomycete isolates demonstrated antimicrobial and antioxidant activity. Altogether, this study demonstrates that the Estremadura Spur is a source of actinomycetes with potential applications for biotechnology. It highlights the importance of investigating actinomycetes from unique ecosystems, such as pockmarks, as the metabolite production reflects their adaptation to this habitat.
Tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and treatment
2021-12-23

The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase 1-mutated (IDH1-mutated) tumor entities affirmed the role of metabolism in cancer. However, large databases with tissue metabolites that are modulated by IDH1 mutation remain an area of development. Here, we present an unprecedented and valuable resource for tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and tumor treatments in 101 tissue samples from 73 diffuse glioma patients (24 astrocytoma, 17 oligodendroglioma, 32 glioblastoma), investigated by NMR-based metabolomics and supported by RNA-Seq. We discovered comparison-specific metabolites and pathways modulated by IDH1 (IDH1 mutation status cohort) and tumor entity. The Longitudinal investigation cohort provides metabolic profiles of untreated and corresponding treated glioma samples at first progression. Most interestingly, univariate and multivariate cox regressions and Kaplan-Meier analyses revealed that tissue metabolites correlate with progression-free and overall survival. Thus, this study introduces potentially novel candidate prognostic and surrogate metabolite biomarkers for future prospective clinical studies, aiming at further refining patient stratification in diffuse glioma. Furthermore, our data will facilitate the generation of so-far-unanticipated hypotheses for experimental studies to advance our molecular understanding of glioma biology.
Integrated Single-cell and Plasma Proteomic Modeling to Predict Surgical Site Complications: A Prospective Cohort Study
2021-12-23

Objective: The aim of this study was to determine whether single-cell and plasma proteomic elements of the host's immune response to surgery accurately identify patients who develop a surgical site complication (SSC) after major abdominal surgery. Summary Background Data: SSCs may occur in up to 25% of patients undergoing bowel resection, resulting in significant morbidity and economic burden. However, the accurate prediction of SSCs remains clinically challenging. Leveraging high-content proteomic technologies to comprehensively profile patients’ immune response to surgery is a promising approach to identify predictive biological factors of SSCs. Methods: Forty-one patients undergoing non-cancer bowel resection were prospectively enrolled. Blood samples collected before surgery and on postoperative day one (POD1) were analyzed using a combination of single-cell mass cytometry and plasma proteomics. The primary outcome was the occurrence of an SSC, including surgical site infection, anastomotic leak, or wound dehiscence within 30 days of surgery. Results: A multiomic model integrating the single-cell and plasma proteomic data collected on POD1 accurately differentiated patients with (n = 11) and without (n = 30) an SSC [area under the curve (AUC) = 0.86]. Model features included coregulated proinflammatory (eg, IL-6- and MyD88- signaling responses in myeloid cells) and immunosuppressive (eg, JAK/STAT signaling responses in M-MDSCs and Tregs) events preceding an SSC. Importantly, analysis of the immunological data obtained before surgery also yielded a model accurately predicting SSCs (AUC = 0.82). Conclusions: The multiomic analysis of patients’ immune response after surgery and immune state before surgery revealed systemic immune signatures preceding the development of SSCs. Our results suggest that integrating immunological data in perioperative risk assessment paradigms is a plausible strategy to guide individualized clinical care.
A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes
2021-12-23

Abstract Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neuronal cultures. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell–derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.
Dynamics of Apolipoprotein B-100 in Interaction with Detergent Probed by Incoherent Neutron Scattering
2021-12-23

Apolipoprotein B-100 (apo B-100) is the protein moiety of both low- and very-low-density lipoproteins, whose role is crucial to cholesterol and triglyceride transport. Aiming at the molecular dynamics' details of apo B-100, scarcely studied, we performed elastic and quasi-elastic incoherent neutron scattering (EINS, QENS) experiments combining different instruments and time scales. Similar to classical membrane proteins, the solubilization results in remaining detergent, here Nonidet P-40 (NP40). Therefore, we propose a framework for QENS studies of protein-detergent complexes, with the introduction of a combined model, including the experimental apo B-100/NP40 ratio. Relying on the simultaneous analysis of all QENS amplitudes, this approach is sensitive enough to separate both contributions. Its application identified two points: (i) apo B-100 slow dynamics and (ii) the acceleration of NP40 dynamics in the presence of apo B-100. Direct translation of the exposed methodology now makes the investigation of more membrane proteins by neutron spectroscopy achievable.
Defining a Synovial Fluid White Blood Cell Count Threshold to Predict Periprosthetic Infection after Shoulder Arthroplasty
2021-12-23

Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm3 showed a sensitivity of 87% and a specificity of 88% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76% and a specificity of 100%. Conclusions: A threshold of 2800 leucocytes/mm3 in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI.
Somatic Reversion of a Novel IL2RG Mutation Resulting in Atypical X-Linked Combined Immunodeficiency
2021-12-23

Mutations of the IL2RG gene, which encodes for the interleukin-2 receptor common gamma chain (γC, CD132), can lead to X-linked severe combined immunodeficiency (X-SCID) associated with a T−B+NK− phenotype as a result of dysfunctional γC-JAK3-STAT5 signaling. Lately, hypomorphic mutations of the IL2RG gene have been described causing atypical SCID with a milder phenotype. Here, we report three brothers with low-normal lymphocyte counts and susceptibility to recurrent respiratory infections and cutaneous warts. The clinical presentation combined with dysgammaglobulinemia suspected an inherited immunity disorder, which has been proven by Next Generation Sequencing as a novel c.458T &gt; C; p.Ile153Thr IL2RG missense-mutation. Subsequent functional characterization revealed impaired T-cell proliferation, low TREC levels and a skewed TCR Vβ repertoire in all three patients. Interestingly, investigation of various subpopulations showed normal expression of CD132 but with partially impaired STAT5 phosphorylation compared to healthy controls. Additionally, we performed precise genetic analysis of subpopulations revealing spontaneous somatic reversion, predominately in lymphoid derived CD3+, CD4+ and CD8+ T cells. Our data demonstrate that the atypical SCID phenotype noticed in these three brothers is due to the combination of hypomorphic IL-2RG function and somatic reversion.