bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of body mass index changes from childhood to adulthood with dyslipidemia in adults: Hanzhong adolescent cohort study
Authors: Liao Yue-Yuan , Chu Chao , Wang Yang , Zheng Wen-Ling , Ma Qiong , Hu Jia-Wen , Yan Yu , Wang Ke-Ke , Yuan Yue , Chen Chen , Mu Jian-Jun 
Published: June 2020

Abstract

Background
Dyslipidemia is a disorder of lipid metabolism and associated with insulin resistance. The relationship between longitudinal body mass index (BMI) changes from childhood to adulthood and long-term dyslipidemia was explored in this study.

Methods
We assessed the longitudinal relationship between BMI changes since childhood and dyslipidemia among 1738 participants in rural areas of Hanzhong City, Shaanxi. All participants were initially examined between the ages of 6 and 15 years in 1987 and were reexamined in 1995, 2013 and 2017; the total follow-up duration was 30 years. Anthropometric measurements and blood biochemistry indexes were measured.

Results
We found that gradual progression of normal weight to overweight (OR = 1.65; 95% CI = 1.27, 2.15) or persistent overweight (OR = 2.45; 95% CI = 1.52, 3.96) from childhood to adulthood was associated with an increased risk of dyslipidemia in adulthood. And these risks were largely disappeared if the overweight or obesity during childhood was resolved by adulthood. The higher the BMI in adulthood and the younger the age at which overweight begins, the higher the risk of dyslipidemia.

Conclusions
Early weight loss and any degree of weight loss from childhood to adulthood can help improve dyslipidemia in adulthood. We further emphasize the importance of weight management and control in public health primary prevention.
Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study
Authors: Ferruccio Naika P , Tosato Sarah , Lappin Julia M , Heslin Margaret , Donoghue Kim , Giordano Annalisa , Lomas Ben , Reininghaus Ulrich , Onyejiaka Adanna , Chan Raymond C K , Croudace Tim , Jones Peter B , Murray Robin M , Fearon Paul , Doody Gillian A , Morgan Craig , Dazzan Paola 
Published: June 2020

AbstractMinor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.
Out of Sight, Out of Mind: Widespread Nuclear and Plastid-Nuclear Discordance in the Flowering Plant GenusPolemonium(Polemoniaceae) Suggests Widespread Historical Gene Flow Despite Limited Nuclear Signal
Authors: Rose Jeffrey P , Toledo Cassio A P , Lemmon Emily Moriarty , Lemmon Alan R , Sytsma Kenneth J 
Published: June 2020

AbstractPhylogenomic data from a rapidly increasing number of studies provide new evidence for resolving relationships in recently radiated clades, but they also pose new challenges for inferring evolutionary histories. Most existing methods for reconstructing phylogenetic hypotheses rely solely on algorithms that only consider incomplete lineage sorting (ILS) as a cause of intra- or intergenomic discordance. Here, we utilize a variety of methods, including those to infer phylogenetic networks, to account for both ILS and introgression as a cause for nuclear and cytoplasmic-nuclear discordance using phylogenomic data from the recently radiated flowering plant genus Polemonium (Polemoniaceae), an ecologically diverse genus in Western North America with known and suspected gene flow between species. We find evidence for widespread discordance among nuclear loci that can be explained by both ILS and reticulate evolution in the evolutionary history of Polemonium. Furthermore, the histories of organellar genomes show strong discordance with the inferred species tree from the nuclear genome. Discordance between the nuclear and plastid genome is not completely explained by ILS, and only one case of discordance is explained by detected introgression events. Our results suggest that multiple processes have been involved in the evolutionary history of Polemonium and that the plastid genome does not accurately reflect species relationships. We discuss several potential causes for this cytoplasmic-nuclear discordance, which emerging evidence suggests is more widespread across the Tree of Life than previously thought. [Cyto-nuclear discordance, genomic discordance, phylogenetic networks, plastid capture, Polemoniaceae, Polemonium, reticulations.]
A Set of Six Gene Expression Biomarkers Identify Rat Liver Tumorigens in Short-term Assays
Authors: Corton J Christopher , Hill Thomas , Sutherland Jeffrey J , Stevens James L , Rooney John 
Published: June 2020

AbstractChemical-induced liver cancer occurs in rodents through well-characterized adverse outcome pathways. We hypothesized that measurement of the 6 most common molecular initiating events (MIEs) in liver cancer adverse outcome pathways in short-term assays using only gene expression will allow early identification of chemicals and their associated doses that are likely to be tumorigenic in the liver in 2-year bioassays. We tested this hypothesis using transcript data from a rat liver microarray compendium consisting of 2013 comparisons of 146 chemicals administered at doses with previously established effects on rat liver tumor induction. Five MIEs were measured using previously characterized gene expression biomarkers composed of gene sets predictive for genotoxicity and activation of 1 or more xenobiotic receptors (aryl hydrocarbon receptor, constitutive activated receptor, estrogen receptor, and peroxisome proliferator-activated receptor α). Because chronic injury can be important in tumorigenesis, we also developed a biomarker for cytotoxicity that had a 96% balanced accuracy. Characterization of the genes in each biomarker set using the unsupervised TXG-MAP network model demonstrated that the genes were associated with distinct functional coexpression modules. Using the Toxicological Priority Index to rank chemicals based on their ability to activate the MIEs showed that chemicals administered at tumorigenic doses clearly gave the highest ranked scores. Balanced accuracies using thresholds derived from either TG-GATES or DrugMatrix data sets to predict tumorigenicity in independent sets of chemicals were up to 93%. These results show that a MIE-directed approach using only gene expression biomarkers could be used in short-term assays to identify chemicals and their doses that cause tumors.
Aneugen Versus Clastogen Evaluation and Oxidative Stress-Related Mode-of-Action Assessment of Genotoxic Compounds Using the ToxTracker Reporter Assay
Authors: Brandsma Inger , Moelijker Nynke , Derr Remco , Hendriks Giel 
Published: June 2020

Abstract
Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with genotoxicity and cancer. ToxTracker consists of 6 different GFP reporter cell lines that can detect the induction of DNA damage, oxidative stress, and protein damage in a single test. The assay can thereby provide insight into the MOA of compounds. Genotoxicity is detected in ToxTracker by activation of 2 independent GFP reporters. Activation of the Bscl2-GFP reporter is associated with induction of DNA adducts and subsequent inhibition of DNA replication and the Rtkn-GFP reporter is activated following the formation of DNA double-strand breaks. Here, we show that the differential activation of these 2 genotoxicity reporters could be used to further differentiate between a DNA reactive and clastogenic or a non-DNA-reactive aneugenic MOA of genotoxic compounds. For further classification of aneugenic and clastogenic compounds, the ToxTracker assay was extended with cell cycle analysis and aneuploidy assessment. The extension was validated using a selection of 16 (genotoxic) compounds with a well-established MOA. Furthermore, indirect genotoxicity related to the production of reactive oxygen species was investigated using the DNA damage and oxidative stress ToxTracker reporters in combination with different reactive oxygen species scavengers. With these new extensions, ToxTracker was able to accurately classify compounds as genotoxic or nongenotoxic and could discriminate between DNA-reactive compounds, aneugens, and indirect genotoxicity caused by oxidative stress.
Reliable Assessment of Surgical Technical Skills Is Dependent on Context: An Exploration of Different Variables Using Generalizability Theory
Authors: Andersen Steven Arild Wuyts , Park Yoon Soo , Sørensen Mads Sølvsten , Konge Lars 
Published: June 2020

Purpose
Reliable assessment of surgical skills is vital for competency-based medical training. Several factors influence not only the reliability of judgments but also the number of observations needed for making judgments of competency that are both consistent and reproducible. The aim of this study was to explore the role of various conditions—through the analysis of data from large-scale, simulation-based assessments of surgical technical skills—by examining the effects of those conditions on reliability using generalizability theory.

Method
Assessment data from large-scale, simulation-based temporal bone surgical training research studies in 2012–2018 were pooled, yielding collectively 3,574 assessments of 1,723 performances. The authors conducted generalizability analyses using an unbalanced random-effects design, and they performed decision studies to explore the effect of the different variables on projections of reliability.

Results
Overall, 5 observations were needed to achieve a generalizability coefficient > 0.8. Several variables modified the projections of reliability: increased learner experience necessitated more observations (5 for medical students, 7 for residents, and 8 for experienced surgeons), the more complex cadaveric dissection required fewer observations than virtual reality simulation (2 vs 5 observations), and increased fidelity simulation graphics reduced the number of observations needed from 7 to 4. The training structure (either massed or distributed practice) and simulator-integrated tutoring had little effect on reliability. Finally, more observations were needed during initial training when the learning curve was steepest (6 observations) compared with the plateau phase (4 observations).

Conclusions
Reliability in surgical skills assessment seems less stable than it is often reported to be. Training context and conditions influence reliability. The findings from this study highlight that medical educators should exercise caution when using a specific simulation-based assessment in other contexts.
The University of Miami Infectious Disease Elimination Act Syringe Services Program: A Blueprint for Student Advocacy, Education, and Innovation
Authors: Tookes Hansel , Bartholomew Tyler S. , St. Onge Joan E. , Ford Henri 
Published: June 2020

After the closure of pill mills and implementation of Florida’s Prescription Drug Monitoring Program in 2010, high demand for opioids was met with counterfeit pills, heroin, and fentanyl. In response, medical students at the University of Miami Miller School of Medicine embarked on a journey to bring syringe services programs (SSPs) to Florida through an innovative grassroots approach. Working with the Florida Medical Association, students learned patient advocacy, legislation writing, and negotiation within a complex political climate. Advocacy over 4 legislative sessions (2013–2016) included committee testimony and legislative visit days, resulting in the authorization of a 5-year SSP pilot.
The University of Miami’s Infectious Disease Elimination Act (IDEA) SSP opened on December 1, 2016. Students identified an urgent need for expanded health care for program participants and founded a weekly free clinic at the SSP. Students who rotate through the clinic learn medicine and harm reduction through the lens of social justice, with exposure to people who use drugs, sex workers, individuals experiencing homelessness, and other vulnerable populations. The earliest success of the IDEA SSP was the distribution of over 2,000 boxes of nasal naloxone, which the authors believe positively contributed to a decrease in the number of opioid-related deaths in Miami-Dade County for the first time since 2013. The second was the early identification of a cluster of acute human immunodeficiency virus infections among program participants.
Inspired by these successes, students from across the state joined University of Miami students and met with legislators in their home districts, wrote op-eds, participated in media interviews, and traveled to the State Capitol to advocate for decisive action to mitigate the opioid crisis. The 2019 legislature passed legislation authorizing SSPs statewide. In states late to adopt SSPs, medical schools have a unique opportunity to address the opioid crisis using this evidence-based approach.
Paracoccus xiamenensis sp. nov., isolated from seawater on the Xiamen
Authors: Lyu Lina , Zhi Bin , Lai Qiliang , Shao Zongze , Yu Zhiqiang 
Published: June 2020

Strain 12-3T was isolated from seawater of the Guanyinshan Coast, Xiamen, Fujian Province, PR China. The bacterium was Gram-stain-negative, rod-shaped, aerobic, oxidase-positive and catalase-negative. Growth of strain 12-3T occurred at 10–37 °C (optimum, 20–30 °C), at pH 5.0–11.0 (optimum, pH 7.0–8.0) and at a salinity range of 0–10 % (optimum, 3–5 %). The results of phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain 12-3T belonged to the genus

Paracoccus

and had the highest sequence similarity to

Paracoccus lutimaris

HDM-25T (97.4 %), followed by

Paracoccus isoporae

SW-3T (96.9 %),

Paracoccus caeni

MJ17T (96.9 %),

Paracoccus pacificus

F14T (96.8 %) and other species in the genus

Paracoccus

(95.3–96.5 %). The average nucleotide identity (ANI) and DNA–DNA hybridization (DDH) values between strain 12-3T and

P. lutimaris

HDM-25T were 76.1 and 17.0 %, respectively. ANI and DDH values between strain 12-3T and

P. isoporae

SW-3T were 78.9 and 18.2 %, respectively. The principal fatty acid of strain 12-3T was summed feature 8 (C18 : 1
ω6c/ω7c) and C18 : 0. The respiratory quinone of strain 12-3T was Q10. The polar lipids included phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid. The G+C content of the chromosomal DNA was 63.9 mol%. The combination of the results of the phylogenetic, phenotypic and chemotaxonomic analyses, and its low ANI and DDH values indicate that strain 12-3T represents a novel species of the genus

Paracoccus

, for which the name Paracoccus xiamenensis sp. nov. is proposed. The type strain is 12-3T (=MCCC 1A16381T=KCTC 72687T).
A novelin vitro Caenorhabditis eleganstranscription system
Authors: Wibisono Phillip , Liu Yiyong , Sun Jingru 
Published: June 2020

AbstractCaenorhabditis elegansis an excellent model organism for biological research, but its contributions to biochemical elucidation of eukaryotic transcription mechanisms have been limited. One of the biggest obstacles for biochemical studies ofC. elegansis the high difficulty of preparing functionally active nuclear extract due to its thick surrounding cuticle. By employing Balch homogenization, we have achieved effective disruption of larval and adult worms and have obtained functionally active nuclear extract through subcellular fractionation.In vitrotranscription reactions were successfully re-constituted using such nuclear extract. Furthermore, two non-radioactive detection methods, PCR and qRT-PCR, have been adapted into our system to qualitatively and quantitatively detect transcription, respectively. Using this system to assess how pathogen infection affectsC. eleganstranscription revealed thatPseudomonas aeruginosainfection increased transcription activity. Ourin vitrosystem is useful for biochemically studyingC. eleganstranscription mechanisms and gene expression regulations. The effective preparation of functionally active nuclear extract in our system fills a technical gap in biochemical studies ofC. elegansand will expand the usefulness of this model organism in addressing many biological questions beyond transcription.
InstantDL - An easy-to-use deep learning pipeline for image segmentation and classification
Authors: Waibel Dominik , Boushehri Sayedali Shetab , Marr Carsten 
Published: June 2020

AbstractMotivationDeep learning contributes to uncovering and understanding molecular and cellular processes with highly performant image computing algorithms. Convolutional neural networks have become the state-of-the-art tool to provide accurate, consistent and fast data processing. However, published algorithms mostly solve only one specific problem and they often require expert skills and a considerable computer science and machine learning background for application.ResultsWe have thus developed a deep learning pipeline called InstantDL for four common image processing tasks: semantic segmentation, instance segmentation, pixel-wise regression and classification. InstantDL enables experts and non-experts to apply state-of-the-art deep learning algorithms to biomedical image data with minimal effort. To make the pipeline robust, we have automated and standardized workflows and extensively tested it in different scenarios. Moreover, it allows to assess the uncertainty of predictions. We have benchmarked InstantDL on seven publicly available datasets achieving competitive performance without any parameter tuning. For customization of the pipeline to specific tasks, all code is easily accessible.Availability and ImplementationInstantDL is available under the terms of MIT licence. It can be found on GitHub:https://github.com/marrlab/InstantDLContactcarsten.marr@helmholtz-muenchen.de
Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis
Authors: Srinivasan Mythily , Zunt Susan L , Goldblatt Lawrence I 
Published: June 2020

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses the angiotensin converting enzyme (ACE)-2 as the host receptor for target cell entry. The extent and distribution of ACE-2 has been associated with the clinical symptoms of coronavirus disease (COVID)-19. Here we show by immunofluorescence analysis that the ACE2 is abundantly expressed in oral mucosa, particularly in the surface epithelial cells suggesting that these cells could represent sites of entry for SARS-CoV-2. Further, together with the reports on ACE2 ectodomain shedding, we discuss the rationale for the hypothesis that the ACE-2 measurement in saliva could be a marker for COVID-19 infection during early phase following SARS-CoV-2 exposure.
CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2
Authors: Amraei Razie , Yin Wenqing , Napoleon Marc A. , Suder Ellen L. , Berrigan Jacob , Zhao Qing , Olejnik Judith , Chandler Kevin Brown , Xia Chaoshuang , Feldman Jared , Hauser Blake M. , Caradonna Timothy M. , Schmidt Aaron G. , Gummuluru Suryaram , Muhlberger Elke , Chitalia Vipul , Costello Catherine E. , Rahimi Nader 
Published: June 2020

AbstractAs the COVID-19 pandemic continues to spread, investigating the processes underlying the interactions between SARS-CoV-2 and its hosts is of high importance. Here, we report the identification of CD209L/L-SIGN and the related protein CD209/DC-SIGN as receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed prominent expression of CD209L in the lung and kidney epithelium and endothelium. Multiple biochemical assays using a purified recombinant SARS-CoV-2 spike receptor binding domain (S-RBD) or S1 encompassing both NTB and RBD and ectopically expressed CD209L and CD209 revealed that CD209L and CD209 interact with S-RBD. CD209L contains twoN-glycosylation sequons, at sites N92 and N361, but we determined that only site N92 is occupied. Removal of theN-glycosylation at this site enhances the binding of S-RBD with CD209L. CD209L also interacts with ACE2, suggesting a role for heterodimerization of CD209L and ACE2 in SARS-CoV-2 entry and infection in cell types where both are present. Furthermore, we demonstrate that human endothelial cells are permissive to SARS-CoV-2 infection and interference with CD209L activity by knockdown strategy or with soluble CD209L inhibits virus entry. Our observations demonstrate that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This property is particularly important in tissues where ACE2 has low expression or is absent, and may have implications for antiviral drug development.
epiGBS2: an improved protocol and automated snakemake workflow for highly multiplexed reduced representation bisulfite sequencing
Authors: Gawehns Fleur , Postuma Maarten , van Gurp Thomas P. , Wagemaker Niels C. A. M. , Fatma Samar , Van Antro Morgane , Mateman Christa , Milanovic-Ivanovic Slavica , van Oers Kees , Grosse Ivo , Vergeer Philippine , Verhoeven Koen J. F. 
Published: June 2020

AbstractepiGBS is an existing reduced representation bisulfite sequencing method to determine cytosine methylation and genetic polymorphismsde novo. Here, we present epiGBS2, an improved epiGBS laboratory protocol and user-friendly bioinformatics pipeline for a wide range of species with or without reference genome. epiGBS2 decreases costs and time investment and increases user-friendliness and reproducibility. The library protocol was adjusted to allow for a flexible choice of restriction enzymes and a double digest. Instead of fully methylated adapters, semi-methylated adapters are now used. The bioinformatics pipeline was improved in speed and integrated in the snakemake workflow management system, which now makes the pipeline easy to execute, modular, and parameter settings flexible. We also provide a detailed description of the laboratory protocol, an extensive manual of the bioinformatics pipeline, which is publicly accessible on github (https://github.com/nioo-knaw/epiGBS2) and zenodo (https://doi.org/10.5281/zenodo.3819996), and example output.