julilili42/papers huggingface dataset:
Facile Patterning of Thermoplastic Elastomers and Robust Bonding to Glass and Thermoplastics for Microfluidic Cell Culture and Organ-on-Chip
2021-05-18

The emergence and spread of microfluidics over the last decades relied almost exclusively on the elastomer polydimethylsiloxane (PDMS). The main reason for the success of PDMS in the field of microfluidic research is its suitability for rapid prototyping and simple bonding methods. PDMS allows for precise microstructuring by replica molding and bonding to different substrates through various established strategies. However, large-scale production and commercialization efforts are hindered by the low scalability of PDMS-based chip fabrication and high material costs. Furthermore, fundamental limitations of PDMS, such as small molecule absorption and high water evaporation, have resulted in a shift toward PDMS-free systems. Thermoplastic elastomers (TPE) are a promising alternative, combining properties from both thermoplastic materials and elastomers. Here, we present a rapid and scalable fabrication method for microfluidic systems based on a polycarbonate (PC) and TPE hybrid material. Microstructured PC/TPE-hybrid modules are generated by hot embossing precise features into the TPE while simultaneously fusing the flexible TPE to a rigid thermoplastic layer through thermal fusion bonding. Compared to TPE alone, the resulting, more rigid composite material improves device handling while maintaining the key advantages of TPE. In a fast and simple process, the PC/TPE-hybrid can be bonded to several types of thermoplastics as well as glass substrates. The resulting bond strength withstands at least 7.5 bar of applied pressure, even after seven days of exposure to a high-temperature and humid environment, which makes the PC/TPE-hybrid suitable for most microfluidic applications. Furthermore, we demonstrate that the PC/TPE-hybrid features low absorption of small molecules while being biocompatible, making it a suitable material for microfluidic biotechnological applications.
Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies
2021-05-18

The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.
Molecular Networking Leveraging the Secondary Metabolomes Space of Halophila stipulaceae (Forsk.) Aschers. and Thalassia hemprichii (Ehrenb. ex Solms) Asch. in Tandem with Their Chemosystematics and Antidiabetic Potentials
2021-05-18

The Red Sea is one of the most biodiverse aquatic ecosystems. Notably, seagrasses possess a crucial ecological significance. Among them are the two taxa Halophila stipulacea (Forsk.) Aschers., and Thalassia hemprichii (Ehrenb. ex Solms) Asch., which were formally ranked together with the genus Enhalus in three separate families. Nevertheless, they have been recently classified as three subfamilies within Hydrocharitaceae. The interest of this study is to explore their metabolic profiles through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS/MS) analysis in synergism with molecular networking and to assess their chemosystematics relationship. A total of 144 metabolites were annotated, encompassing phenolic acids, flavonoids, terpenoids, and lipids. Furthermore, three new phenolic acids; methoxy benzoic acid-O-sulphate (16), O-caffeoyl-O-hydroxyl dimethoxy benzoyl tartaric acid (26), dimethoxy benzoic acid-O-sulphate (30), a new flavanone glycoside; hexahydroxy-monomethoxy flavanone-O-glucoside (28), and a new steviol glycoside; rebaudioside-O-acetate (96) were tentatively described. Additionally, the evaluation of the antidiabetic potential of both taxa displayed an inherited higher activity of H. stipulaceae in alleviating the oxidative stress and dyslipidemia associated with diabetes. Hence, the current research significantly suggested Halophila, Thalassia, and Enhalus categorization in three different taxonomic ranks based on their intergeneric and interspecific relationship among them and supported the consideration of seagrasses in natural antidiabetic studies.
Intrinsic timescales in the visual cortex change with selective attention and reflect spatial connectivity
2021-05-18

ABSTRACT Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 while monkeys performed spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.
CUX1 Enhances Pancreatic Cancer Formation by Synergizing with KRAS and Inducing MEK/ERK-Dependent Proliferation
2021-05-18

The transcription factor CUX1 has been implicated in either tumor suppression or progression, depending on the cancer entity and the prevalent CUX1 isoform. Previously, we could show that CUX1 acts as an important mediator of tumor cell proliferation and resistance to apoptosis in pancreatic cancer cell lines. However, in vivo evidence for its impact on pancreatic carcinogenesis, isoform-specific effects and downstream signaling cascades are missing. We crossbred two different CUX1 isoform mouse models (p200 CUX1 and p110 CUX1) with KC (KrasLSL-G12D/+; Ptf1aCre/+) mice, a genetic model for pancreatic precursor lesions (PanIN). In the context of oncogenic KRASs, both mice KCCux1p200 and KCCux1p110 led to increased PanIN formation and development of invasive pancreatic ductal adenocarcinomata (PDAC). In KCCux1p110 mice, tumor development was dramatically more accelerated, leading to formation of invasive PDAC within 4 weeks. In vitro and in vivo, we could show that CUX1 enhanced proliferation by activating MEK-ERK signaling via an upstream increase of ADAM17 protein, which in turn led to an activation of EGFR. Additionally, CUX1 further enhanced MEK-ERK activation through upregulation of the serine/threonine kinase MOS, phosphorylating MEK in a KRAS-independent manner. We identified p110 CUX1 as major driver of pancreatic cancer formation in the context of mutant KRAS. These results provide the first in vivo evidence for the importance of CUX1 in the development of pancreatic cancer, and highlight the importance of CUX1-dependent signaling pathways as potential therapeutic targets.
Evaluation of a Three-Marker Panel for the Detection of Uveal Melanoma Metastases: A Single-Center Retrospective Analysis
2021-05-18

Blood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been identified to be promising biomarkers for the metastases of uveal melanoma (UM). This study intended to assess their kinetics and to evaluate their significance as a three-marker panel. A group of 36 UM patients with and 137 patients without metastases were included in the study. Their plasma OPN levels were measured by ELISA; serum BAFF and GDF-15 levels were determined with a Luminex MAGPIX system. Receiver operating characteristic (ROC) analysis was performed to calculate the cutoff values of the three markers for identifying the patients with metastases. The ability to identify patients with metastases was compared between the single markers and the combination as a three-marker panel. By using the Student’s t-test, we also investigated the kinetic changes of the levels of BAFF, GDF-15 and OPN across six periods (i.e., 0–6 months, 6–12 months, 12–18 months, 18–24 months, &gt;24 months and post-metastasis) before the imaging diagnosis of metastases. By maximizing the Youden’s index, the serum GDF-15 level of 1209 pg/mL and the plasma OPN level of 92 ng/mL were identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. The three-marker panel offered a better performance in distinguishing patients with metastases, with an area under the curve of 0.802, than any single biomarker. Increasing trends of the levels of three biomarkers were observed in the two-year period before the imaging diagnosis of metastases. The combined panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. In the bioinformatics study with two external datasets, the high expression of gene BAFF and GDF-15 in primary UM tissues was identified to be associated with poor overall survival rates. As the current work is a single-center retrospective study, more well-designed prospective investigations employing larger cohorts are urgently needed to validate our findings.
ESCAPED: Efficient Secure and Private Dot Product Framework for Kernel-based Machine Learning Algorithms with Applications in Healthcare
2021-05-18

Training sophisticated machine learning models usually requires many training samples. Especially in healthcare settings these samples can be very expensive, meaning that one institution alone usually does not have enough. Merging privacy-sensitive data from different sources is usually restricted by data security and data protection measures. This can lead to approaches that reduce data quality by putting noise onto the variables (e.g., in epsilon-differential privacy) or omitting certain values (e.g., for k-anonymity). Other measures based on cryptographic methods can lead to very time-consuming computations, which is especially problematic for larger multi-omics data. We address this problem by introducing ESCAPED, which stands for Efficient SeCure And PrivatE Dot product framework. ESCAPED enables the computation of the dot product of vectors from multiple sources on a third-party, which later trains kernel-based machine learning algorithms, while neither sacrificing privacy nor adding noise. We have evaluated our framework on drug resistance prediction for HIV-infected people and multi-omics dimensionality reduction and clustering problems in precision medicine. In terms of execution time, our framework significantly outperforms the best-fitting existing approaches without sacrificing the performance of the algorithm. Even though we only present the benefit for kernel-based algorithms, our framework can open up new research opportunities for further machine learning models that require the dot product of vectors from multiple sources.
Computational Treatment Simulations to Assess the Need for Personalized Tamoxifen Dosing in Breast Cancer Patients of Different Biogeographical Groups
2021-05-18

Tamoxifen is used worldwide to treat estrogen receptor-positive breast cancer. It is extensively metabolized, and minimum steady-state concentrations of its metabolite endoxifen (CSS,min ENDX) &gt;5.97 ng/mL have been associated with favorable outcome. Endoxifen formation is mediated by the enzyme CYP2D6, and impaired CYP2D6 function has been associated with lower CSS,min ENDX. In the Women’s Healthy Eating and Living (WHEL) study proposing the target concentration, 20% of patients showed subtarget CSS,min ENDX at tamoxifen standard dosing. CYP2D6 allele frequencies vary largely between populations, and as 87% of the patients in the WHEL study were White, little is known about the risk for subtarget CSS,min ENDX in other populations. Applying pharmacokinetic simulations, this study investigated the risk for subtarget CSS,min ENDX at tamoxifen standard dosing and the need for dose individualization in nine different biogeographical groups with distinct CYP2D6 allele frequencies. The high variability in CYP2D6 allele frequencies amongst the biogeographical groups resulted in an up to three-fold difference in the percentages of patients with subtarget CSS,min ENDX. Based on their CYP2D6 allele frequencies, East Asian breast cancer patients were identified as the population for which personalized, model-informed precision dosing would be most beneficial (28% of patients with subtarget CSS,min ENDX).
Multimodal host-guest complexation for efficient and stable perovskite photovoltaics
2021-05-18

Structural, optoelectronic, photovoltaic, and other characterization data for “Multimodal host-guest complexation for efficient and stable perovskite photovoltaics”, DOI:10.1038/s41467-021-23566-2. <strong>Fig_source_data.zip: </strong>Data described in Fig. 1–5 as Excel (*.xlsx) and image (*.tiff) files, as well as the file structure of the TopSpin software available from Bruker. <strong>Fig_SI.zip:</strong> Data described in the Supplementary Information as Origin (*.opj), text (*.txt), image (*.tif) files, and the file structure of the TopSpin software available from Bruker. <strong>MD_files.zip: </strong>Molecular dynamics simulations as *.cif files. <strong>DFT_files.zip: </strong>DFT calculations as *.cif files.
Advancing Research on Unconscious Priming: When can Scientists Claim an Indirect Task Advantage?
2021-05-18

Current literature holds that many cognitive functions can be performed outside consciousness. Evidence for this view comes from unconscious priming. In a typical experiment, visual stimuli are masked such that participants are close to chance performance when directly asked to which of two categories the stimuli belong. This close-to-zero sensitivity is seen as evidence that participants cannot consciously report the category of the masked stimuli. Nevertheless, the category of the masked stimuli can indirectly affect responses to other stimuli (e.g., reaction times or brain activity)—an effect called priming. The priming effect is seen as evidence for a higher sensitivity to the masked stimuli in the indirect responses as compared to the direct responses. Such an apparent difference in sensitivities is taken as evidence that processing occurred unconsciously. But we show that this “standard reasoning of unconscious priming” is flawed: Sensitivities are not properly compared, creating the wrong impression of a difference in sensitivities even if there is none. We describe the appropriate way to determine sensitivities, replicate the behavioral part of a landmark study, develop methods to estimate sensitivities from reported summary statistics of published studies, and use these methods to reanalyze 15 highly influential studies. Results show that the interpretations of many studies need to be changed and that a community effort is required to reassess the vast literature on unconscious priming. This process will allow scientists to learn more about the true boundary conditions of unconscious priming, thereby advancing the scientific understanding of consciousness.
Comment on esurf-2021-22
2021-05-18

<strong class="journal-contentHeaderColor">Abstract.</strong> Weathering of bedrock to produce regolith is essential for sustaining life on Earth and global biogeochemical cycles. The rate of this process is influenced not only by tectonics, but also by climate and biota. We present new data on soil production, chemical weathering, and physical erosion rates from the large climate and ecological gradient of the Chilean Coastal Cordillera (26Â to 38<span class="inline-formula"><sup>â</sup></span>âS). Four Chilean study areas are investigated and span (from north to south) arid (Pan de AzÃocar), semi-arid (Santa Gracia), Mediterranean (LaÂ Campana), and temperate humid (Nahuelbuta) climate zones. Observed soil production rates in granitoid soil-mantled hillslopes range from <span class="inline-formula">â1⁄47</span>Â to 290âtâkm<span class="inline-formula"><sup>â2</sup></span>âyr<span class="inline-formula"><sup>â1</sup></span> and are lowest in the sparsely vegetated and arid north and highest in the Mediterranean setting. Calculated chemical weathering rates range from zero in the arid north to a high of 211âtâkm<span class="inline-formula"><sup>â2</sup></span>âyr<span class="inline-formula"><sup>â1</sup></span> in the Mediterranean zone. Chemical weathering rates are moderate in the semi-arid and temperate humid zones (<span class="inline-formula">â1⁄420</span>Â to 50âtâkm<span class="inline-formula"><sup>â2</sup></span>âyr<span class="inline-formula"><sup>â1</sup></span>). Similarly, physical erosion rates are lowest in the arid zone (<span class="inline-formula">â1⁄411</span>âtâkm<span class="inline-formula"><sup>â2</sup></span>âyr<span class="inline-formula"><sup>â1</sup></span>) and highest in the Mediterranean climate zone (<span class="inline-formula">â1⁄491</span>âtâkm<span class="inline-formula"><sup>â2</sup></span>âyr<span class="inline-formula"><sup>â1</sup></span>). The contribution of chemical weathering to total denudation rates is lower in the arid north than further south. However, due to heterogeneities in lithologies and ZrÂ concentrations, reported chemical weathering rates and chemical depletion fractions are affected by large uncertainties. Comparison of Chilean results to published global data collected from hillslope settings underlain by granitoid lithologies documents similar patterns in soil production, chemical weathering, and total denudation rates for varying mean annual precipitation and vegetation cover amounts. We discuss the Chilean and global data in the light of contending model frameworks in the literature and find that observed variations in soil production rates bear the closest resemblance to models explicitly accounting for variations in soil thickness and biomass.
Ratio Between Lactobacillus Plantarum and Acetobacter Pomorum on the Surface of Drosophila Melanogaster Adult Flies Depends on Cuticle Melanisation
2021-05-18

<title>Abstract</title> Objectives As in most organisms, the surface of the fruit fly Drosophila melanogaster is associated with bacteria. In order to study the genetic parameters of this association, we developed a simple protocol for surface bacteria isolation and quantification. Results On wild-type flies maintained in the laboratory, we identified two persistently culturable species as Lactobacillus plantarum and Acetobacter pomorum by 16S rDNA sequencing. For quantification, we showered single flies for DNA extraction avoiding the rectum to prevent contamination from the gut. Using specific primers for quantitative PCR analyses, we determined the relative abundance of these two species in surface wash samples. Repeatedly, we found 20% more L. plantarum than A. pomorum . To tentatively study the importance of the cuticle for the interaction of the surface with these bacteria, applying Crispr/Cas9 gene editing in the initial wild-type flies, we generated flies mutant for the ebony gene needed for cuticle melanisation and determined the L. plantarum to A. pomorum ratio on these flies. We found that the relative abundance of L. plantarum increased substantially on ebony flies. We conclude that the cuticle chemistry is crucial for surface bacteria composition. This finding may inspire future studies on cuticle-microbiome interactions.
Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy
2021-05-19

Abstract Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug‐related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up‐to‐date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.
Perioperative Pembrolizumab Therapy in Muscle-Invasive Bladder Cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303
2021-05-19

Muscle-invasive bladder cancer (MIBC) is associated with high rates of recurrence and poor prognosis despite aggressive treatment. Neoadjuvant chemotherapy before radical cystectomy (RC) improves outcomes in cisplatin-eligible patients; however, the improvement in overall survival is modest. Standard of care for cisplatin-ineligible patients remains RC; more effective systemic therapies are needed. Recent Phase Ib/II studies suggest pembrolizumab monotherapy and combination therapy are effective neoadjuvant therapies for MIBC. The randomized Phase III KEYNOTE-866 and KEYNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-eligible patients with MIBC (KEYNOTE-866) and of pembrolizumab monotherapy versus pembrolizumab plus enfortumab vedotin versus RC plus pelvic lymph node dissection alone in cisplatin-ineligible patients with MIBC (KEYNOTE-905/EV-303). <b>Clinical trial registration:</b> NCT03924856 & NCT03924895 (ClinicalTrials.gov).