julilili42/papers huggingface dataset:
External Model Performance Evaluation of Twelve Infliximab Population Pharmacokinetic Models in Patients with Inflammatory Bowel Disease
2021-08-31

Infliximab is approved for treatment of various chronic inflammatory diseases including inflammatory bowel disease (IBD). However, high variability in infliximab trough levels has been associated with diverse response rates. Model-informed precision dosing (MIPD) with population pharmacokinetic models could help to individualize infliximab dosing regimens and improve therapy. The aim of this study was to evaluate the predictive performance of published infliximab population pharmacokinetic models for IBD patients with an external data set. The data set consisted of 105 IBD patients with 336 infliximab concentrations. Literature review identified 12 published models eligible for external evaluation. Model performance was evaluated with goodness-of-fit plots, prediction- and variability-corrected visual predictive checks (pvcVPCs) and quantitative measures. For anti-drug antibody (ADA)-negative patients, model accuracy decreased for predictions &gt; 6 months, while bias did not increase. In general, predictions for patients developing ADA were less accurate for all models investigated. Two models with the highest classification accuracy identified necessary dose escalations (for trough concentrations &lt; 5 μg/mL) in 88% of cases. In summary, population pharmacokinetic modeling can be used to individualize infliximab dosing and thereby help to prevent infliximab trough concentrations dropping below the target trough concentration. However, predictions of infliximab concentrations for patients developing ADA remain challenging.
Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression
2021-08-31

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.
iPS Cell-Based Model for MAPT Haplotype as a Risk Factor for Human Tauopathies Identifies No Major Differences in TAU Expression
2021-08-31

The H1 haplotype of the microtubule-associated protein tau ( MAPT ) gene is a common genetic risk factor for some neurodegenerative diseases such as progressive supranuclear palsy, corticobasal degeneration, and Parkinson’s disease. The molecular mechanism causing the increased risk for the named diseases, however, remains unclear. In this paper, we present a valuable tool of eight small molecule neural precursor cell lines (smNPC) homozygous for the MAPT haplotypes (four H1/H1 and four H2/H2 cell lines), which can be used to identify MAPT -dependent phenotypes. The employed differentiation protocol is fast due to overexpression of NEUROGENIN-2 and therefore suitable for high-throughput approaches. A basic characterization of all human cell lines was performed, and their TAU and α-SYNUCLEIN profiles were compared during a differentiation time of 30 days. We could identify higher levels of conformationally altered TAU in cell lines carrying the H2 haplotype. Additionally, we found increased expression levels of α-SYNUCLEIN in H1/H1 cells. With this resource, we aim to fill a gap in neurodegenerative disease modeling with induced pluripotent stem cells (iPSC) for sporadic tauopathies.
nf-core/mag: a best-practice pipeline for metagenome hybrid assembly and binning
2021-08-31

ABSTRACT The analysis of shotgun metagenomic data provides valuable insights into microbial communities, while allowing resolution at individual genome level. In absence of complete reference genomes, this requires the reconstruction of metagenome assembled genomes (MAGs) from sequencing reads. We present the nf-core/mag pipeline for metagenome assembly, binning and taxonomic classification. It can optionally combine short and long reads to increase assembly continuity and utilize sample-wise group-information for co-assembly and genome binning. The pipeline is easy to install - all dependencies are provided within containers -, portable and reproducible. It is written in Nextflow and developed as part of the nf-core initiative for best-practice pipeline development. All code is hosted on GitHub under the nf-core organization https://github.com/nf-core/mag and released under the MIT license.
Enhanced Bioavailability of Dihydrotanshinone I–Bovine Serum Albumin Nanoparticles for Stroke Therapy
2021-08-31

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT–BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide–induced oxidative damage in PC12 cells. In addition, DHT–BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT–BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio–cerebrovascular diseases.
The Taphonomy of Echinoids: Skeletal Morphologies, Environmental Factors and Preservation Pathways
2021-08-31

The study of echinoid evolution, diversity, and ecology has always suffered from the fact that they are represented by taxa showing widely differing architectural designs of their multi-plated skeletons, inhabiting a large range of marine paleoenvironments, which result in highly varying taphonomic biases dictating their presence and recognition. This Element addresses the taphonomy of echinoids and includes: a general introduction to the morphological features of echinoids that play a role in their preservation; a review of processes which play an important role in the differential preservation of both regular and irregular echinoids including predation and transport; a summary of taphonomic pathways included in actualistic studies for recent sea urchins and then reconstructed for fossil taxa; and finally, a case study of the variation of echinoid taphonomy across a shelf gradient using the rich Miocene echinoid fauna of Sardinia
Feasibility and Acceptability of a Mobile-Based Emotion Recognition Approach for Bipolar Disorder.
2021-08-31

Over the past years, the mobile Health approach has motivated research projects to develop mood monitoring systems for bipolar disorder. Whereas mobile-based approaches have examined self-assessment or sensor data, so far, potentially important emotional aspects of this disease have been neglected. Thus, we developed an emotion-sensitive system that analyzes the verbal and facial expressions of bipolar patients in regard to their emotional cues. In this article, preliminary findings of a pilot study with five bipolar patients with respect to the acceptability and feasibility of the new approach are presented and discussed. There were individual differences in the usage frequency of the participants, and improvements regarding its handling were suggested. From the technical point of view, the video analysis was less dependable than the audio analysis and recognized almost exclusively the facial expressions of happiness. However, the system was feasible and well-accepted. The results indicate that further developments could facilitate the long-term analysis of expressed emotions in bipolar or other disorders without invading the privacy of patients.
Interface Properties of CoPc on Nanographene-Covered Au(111) and the Influence of Annealing
2021-08-31

Organic bilayer systems and heterostructures are of enormous importance for optoelectronic devices. We study interface properties and the structural ordering of cobalt phthalocyanine (CoPc) on a highly ordered monolayer hexa-peri-hexabenzocoronene (HBC), grown on Au(111), using photoemission, X-ray absorption, scanning tunneling microscopy, and low-energy electron diffraction. A charge transfer between CoPc and the gold substrate is almost completely prevented by the HBC intermediate layer. We show that HBC acts as a template for the initial growth of CoPc molecules. After annealing to 630 K, a molecular exchange takes place, resulting in a coexistence of domains of both CoPc and HBC molecules on the surface.
Synaptotagmin 13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
2021-08-31

Abstract Epithelial cell egression is important for organ development, but also drives cancer metastasis. Better understandings of pancreatic epithelial morphogenetic programs generating islets of Langerhans aid to diabetes therapy. Here we identify the Ca 2+ -independent atypical Synaptotagmin 13 (Syt13) as a key driver of endocrine cell egression and islet formation. We detected upregulation of Syt13 in endocrine precursors that correlates with increased expression of unique cytoskeletal components. High-resolution imaging reveals a previously unidentified apical-basal to front-rear repolarization during endocrine cell egression. Strikingly, Syt13 interacts with acetylated tubulin and phosphatidylinositol phospholipids and localizes to the leading-edge of egressing cells. Knockout of Syt13 impairs endocrine cell egression and skews the α- to-β-cell ratio. Mechanistically, Syt13 regulates endocytosis to remodel the basement membrane and cell-matrix adhesion at the leading-edge of egressing endocrine cells. Altogether, these findings implicate an unexpected role of Syt13 in regulating cell polarity to orchestrate endocrine cell egression and islet morphogenesis.
S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signalling
2021-08-31

Summary Plant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signalling molecules. Receptor kinases are regulated by numerous post-translational modifications. Here, using the immune receptor kinases FLS2 and EFR, we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biophysical properties and behaviour within the membrane environment. We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following perception of its ligand flg22, in a BAK1 co-receptor dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signalling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR supressed elf18 triggered signalling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents and native membrane DIBMA nanodiscs indicates that S-acylation stabilises and promotes retention of activated receptor kinase complexes at the plasma membrane to increase signalling efficiency.
Educational Gender Inequality in Sub‐Saharan Africa: A Long‐Term Perspective
2021-09-01

Abstract To what extent did sub‐Saharan Africa's twentieth century schooling revolution benefit boys and girls equally? Using census data and a cohort approach, we examine gender gaps in years of education over the twentieth century at world region, country and district levels. First, we find that compared to other developing regions, Africa had a small initial educational gender gap but subsequently made the least progress in closing the gap. Second, in most of the 21 African countries studied, gender gaps increased during most of the colonial era (ca. 1880–1960) and declined, albeit at different rates, after independence. At the world region and country level, the expansion of men's education was initially associated with a growing gender gap, and subsequently a decline, a pattern we refer to as “educational gender Kuznets curve.” Third, using data from six decadal cohorts across 1,177 birth districts, we explore subnational correlates of educational gender inequality. This confirms the inverse‐U relationship between the gender gap and male education. We also find that districts with railroads, more urbanization and early twentieth century Christian missions witnessed lower attainment gaps. We find no evidence that cash crop cultivation, agricultural division of labor or family systems were linked to gender gaps.
Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications
2021-09-01

As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.
United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia
2021-09-01

Abstract Background Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. Methods A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as &gt;80% agreement) was reached for 36 statements. Results The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long‐term prognosis and life expectancy are favorable. Conclusions and Inferences A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
Efficient ancestry and mutation simulation with msprime 1.0
2021-09-01

Abstract Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this necessity, a large number of specialised simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and tskit library. We summarise msprime ’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialised alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.
Intelligibility and recall of sentences spoken by adult and child talkers wearing face masks
2021-09-01

With the Covid-19 pandemic, face masks have become part of our daily lives. While face masks are effective in slowing down the spread of the virus, they also make face-to-face communication more challenging. The present study sought to examine the impact of face masks on listeners' intelligibility and recall of sentences produced by one German native adult and one child talker. In the intelligibility task, German native adult listeners watched video clips of either an adult or a child talker producing sentences with and without a face mask. In a cued-recall experiment, another group of German native listeners watched the same video clips and then completed a cued-recall task. The results showed that face masks significantly affected listeners' intelligibility and recall performance, and this effect was equally true for both talkers. The findings here contribute to the fast growing and urgent research regarding the impact of face masks on communication.
A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation
2021-09-01

Abstract The extracellular matrix regulates cell survival, proliferation, and differentiation. In vitro two-dimensional cell experiments are typically performed on a plastic plate or a substrate of a single extracellular matrix constituent such as collagen or calcium phosphate. As these approaches do not include extracellular matrix proteins or growth factors, they fail to mimic a complex cell microenvironment. The cell-derived matrix is an alternative platform for better representing the in vivo microenvironment in vitro. Standard decellularization of a cell-derived matrix is achieved by combining chemical and physical methods. In this study, we compared the decellularization efficacy of several methods: ammonium hydroxide, sodium dodecyl sulfate (SDS), or Triton X-100 with cold or heat treatment on a matrix of Saos-2 cells. We found that the protocols containing SDS were cytotoxic during recellularization. Heat treatment at 47 °C was not cytotoxic, removed cellular constituents, inactivated alkaline phosphatase activity, and maintained the levels of calcium deposition. Subsequently, we investigated the differentiation efficiency of a direct bone coculture system in the established decellularized Saos-2 matrix, an inorganic matrix of calcium phosphate, and a plastic plate as a control. We found that the decellularized Saos-2 cell matrix obtained by heat treatment at 47 °C enhanced osteoclast differentiation and matrix mineralization better than the inorganic matrix and the control. This simple and low-cost method allows us to create a Saos-2 decellularized matrix that can be used as an in vivo-like support for the growth and differentiation of bone cells.
How children learn to communicate discriminatively
2021-09-01

Abstract How do children learn to communicate, and what do they learn? Traditionally, most theories have taken an associative, compositional approach to these questions, supposing children acquire an inventory of form-meaning associations, and procedures for composing / decomposing them; into / from messages in production and comprehension. This paper presents an alternative account of human communication and its acquisition based on the systematic, discriminative approach embodied in psychological and computational models of learning, and formally described by communication theory. It describes how discriminative learning theory offers an alternative perspective on the way that systems of semantic cues are conditioned onto communicative codes, while information theory provides a very different view of the nature of the codes themselves. It shows how the distributional properties of languages satisfy the communicative requirements described in information theory, enabling language learners to align their expectations despite the vastly different levels of experience among language users, and to master communication systems far more abstract than linguistic intuitions traditionally assume. Topics reviewed include morphological development, the acquisition of verb argument structures, and the functions of linguistic systems that have proven to be stumbling blocks for compositional theories: grammatical gender and personal names.