bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cautionary Tale and Update on Breast Implant–Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)
Authors: Ghosh Trina , Duncavage Eric , Mehta-Shah Neha , McGuire Patricia A , Tenenbaum Marissa , Myckatyn Terence M
Published: January 2020

Breast implant–associated anaplastic large T-cell lymphoma (BIA-ALCL) was first recognized by the World Health Organization in 2016. The total number of cases worldwide continues to increase, with >800 cases confirmed through a combination of Food and Drug Administration data, verified reports, and registries. To date, 33 deaths have been reported. Typical presentation includes a late seroma containing monoclonal T cells that are CD30 positive and anaplastic lymphoma kinase negative. We present a review of the current literature and report on 3 cases of BIA-ALCL at our institution, which serve to illustrate our approach to diagnosis and management of this disease. In 2 cases, the diagnosis of BIA-ALCL was not initially confirmed due to an incomplete workup but was recognized upon explantation. The seroma fluid was sent for flow cytometry. Initially, the cells were reported as morphologically suspicious for malignancy with phenotypically normal T cells based on standard CD3+ T-cell gating. Subsequent cytology specimens were reported as consistent with recurrent adenocarcinoma. However, upon regating of flow-cytometry data, a population of CD30+, CD3– T cells was noted and the diagnosis of BIA-ALCL was confirmed by immunohistochemical stains of the excised breast capsule specimen. Given the increasing incidence of this disease, as plastic surgeons we must stay informed to order the correct workup to avoid misdiagnosis and be prepared to appropriately refer affected patients to centers with multidisciplinary teams experienced in the management of BIA-ALCL.

Level of Evidence: 4
The bioinformatics toolbox for circRNA discovery and analysis
Authors: Chen Liang , Wang Changliang , Sun Huiyan , Wang Juexin , Liang Yanchun , Wang Yan , Wong Garry
Published: January 2020

Circular RNAs (circRNAs) are a unique class of RNA molecule identified more than 40 years ago which are produced by a covalent linkage via back-splicing of linear RNA. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field of types and biological functions of circRNAs. In parallel with technological developments, practical applications of circRNAs have arisen including their utilization as biomarkers of human disease. Currently, circRNA-associated bioinformatics tools can support projects including circRNA annotation, circRNA identification and network analysis of competing endogenous RNA (ceRNA). In this review, we collected about 100 circRNA-associated bioinformatics tools and summarized their current attributes and capabilities. We also performed network analysis and text mining on circRNA tool publications in order to reveal trends in their ongoing development.
Closing the circle: current state and perspectives of circular RNA databases
Authors: Vromman Marieke , Vandesompele Jo , Volders Pieter-Jan
Published: January 2020

Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs’ microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.
ChemBioServer 2.0: an advanced web server for filtering, clustering and networking of chemical compounds facilitating both drug discovery and repurposing
Authors: Karatzas Evangelos , Zamora Juan Eiros , Athanasiadis Emmanouil , Dellis Dimitris , Cournia Zoe , Spyrou George M
Published: January 2020

ChemBioServer 2.0 is the advanced sequel of a web server for filtering, clustering and networking of chemical compound libraries facilitating both drug discovery and repurposing. It provides researchers the ability to (i) browse and visualize compounds along with their physicochemical and toxicity properties, (ii) perform property-based filtering of compounds, (iii) explore compound libraries for lead optimization based on perfect match substructure search, (iv) re-rank virtual screening results to achieve selectivity for a protein of interest against different protein members of the same family, selecting only those compounds that score high for the protein of interest, (v) perform clustering among the compounds based on their physicochemical properties providing representative compounds for each cluster, (vi) construct and visualize a structural similarity network of compounds providing a set of network analysis metrics, (vii) combine a given set of compounds with a reference set of compounds into a single structural similarity network providing the opportunity to infer drug repurposing due to transitivity, (viii) remove compounds from a network based on their similarity with unwanted substances (e.g. failed drugs) and (ix) build custom compound mining pipelines.

Availability and implementation

http://chembioserver.vi-seem.eu.
BEM: Mining Coregulation Patterns in Transcriptomics via Boolean Matrix Factorization
Authors: Liang Lifan , Zhu Kunju , Lu Songjian
Published: January 2020

Motivation

The matrix factorization is an important way to analyze coregulation patterns in transcriptomic data, which can reveal the tumor signal perturbation status and subtype classification. However, current matrix factorization methods do not provide clear bicluster structure. Furthermore, these algorithms are based on the assumption of linear combination, which may not be sufficient to capture the coregulation patterns.

Results

We presented a new algorithm for Boolean matrix factorization (BMF) via expectation maximization (BEM). BEM is more aligned with the molecular mechanism of transcriptomic coregulation and can scale to matrix with over 100 million data points. Synthetic experiments showed that BEM outperformed other BMF methods in terms of reconstruction error. Real-world application demonstrated that BEM is applicable to all kinds of transcriptomic data, including bulk RNA-seq, single-cell RNA-seq and spatial transcriptomic datasets. Given appropriate binarization, BEM was able to extract coregulation patterns consistent with disease subtypes, cell types or spatial anatomy.

Availability and implementation

Python source code of BEM is available on https://github.com/LifanLiang/EM_BMF.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Possible Mechanism behind Faster Clearance and Higher Peak Concentrations of Cardiac Troponin I Compared with Troponin T in Acute Myocardial Infarction
Authors: Starnberg Karin , Fridén Vincent , Muslimovic Aida , Ricksten Sven-Erik , Nyström Susanne , Forsgard Niklas , Lindahl Bertil , Vukusic Kristina , Sandstedt Joakim , Dellgren Göran , Hammarsten Ola
Published: January 2020

Background

Although cardiac troponin I (cTnI) and troponin T (cTnT) form a complex in the human myocardium and bind to thin filaments in the sarcomere, cTnI often reaches higher concentrations and returns to normal concentrations faster than cTnT in patients with acute myocardial infarction (MI).

Methods

We compared the overall clearance of cTnT and cTnI in rats and in patients with heart failure and examined the release of cTnT and cTnI from damaged human cardiac tissue in vitro.

Results

Ground rat heart tissue was injected into the quadriceps muscle in rats to simulate myocardial damage with a defined onset. cTnT and cTnI peaked at the same time after injection. cTnI returned to baseline concentrations after 54 h, compared with 168 h for cTnT. There was no difference in the rate of clearance of solubilized cTnT or cTnI after intravenous or intramuscular injection. Renal clearance of cTnT and cTnI was similar in 7 heart failure patients. cTnI was degraded and released faster and reached higher concentrations than cTnT when human cardiac tissue was incubated in 37°C plasma.

Conclusion

Once cTnI and cTnT are released to the circulation, there seems to be no difference in clearance. However, cTnI is degraded and released faster than cTnT from necrotic cardiac tissue. Faster degradation and release may be the main reason why cTnI reaches higher peak concentrations and returns to normal concentrations faster in patients with MI.
Ensemble Technique for Toxicity Prediction of Small Drug Molecules of the Antioxidant Response Element Signalling Pathway
Authors: Kumar Gupta Vishan , Singh Rana Prashant
Published: January 2020

The in-silico toxicity prediction techniques are useful to reduce rodents testing (in-vivo). Authors have proposed a computational method (in silico) for the toxicity prediction of small drug molecules using their various physicochemical properties (molecular descriptors), which can bind to the antioxidant response elements (AREs). The software PaDEL-Descriptor is used for extracting the different features of drug molecules. The ARE data set has total 7439 drug molecules, of which 1147 are active and 6292 are inactive, and each drug molecule contains 1444 features. We have proposed a novel ensemble-based model that can efficiently classify active (binding) and inactive (non-binding) compounds of the data set. Initially, we performed feature selection using random forest importance algorithm in R, and subsequently, we have resolved the class imbalance issue by ensemble learning method itself, where we divided the data set into five data frames, which have an almost equal number of active and inactive drug molecules. An ensemble model based upon the votes of four base classifiers is proposed, which gives an accuracy of 97.14%. The K-fold cross-validation is conducted to measure the consistency of the proposed ensemble model. Finally, the proposed ensemble model is validated on some new drug molecules and compared with some existing models.
Hydra: a method for strain-minimizing hyperbolic embedding of network- and distance-based data
Authors: Keller-Ressel Martin , Nargang Stephanie
Published: January 2020

We introduce hydra (hyperbolic distance recovery and approximation), a new method for embedding network- or distance-based data into hyperbolic space. We show mathematically that hydra satisfies a certain optimality guarantee: it minimizes the ‘hyperbolic strain’ between original and embedded data points. Moreover, it is able to recover points exactly, when they are contained in a low-dimensional hyperbolic subspace of the feature space. Testing on real network data we show that the embedding quality of hydra is competitive with existing hyperbolic embedding methods, but achieved at substantially shorter computation time. An extended method, termed hydra+, typically outperforms existing methods in both computation time and embedding quality.
Parenting in a warming world: thermoregulatory responses to heat stress in an endangered seabird
Authors: Cook Timothée R , Martin Rowan , Roberts Jennifer , Häkkinen Henry , Botha Philna , Meyer Corlia , Sparks Emilee , Underhill Leslie G , Ryan Peter G , Sherley Richard B
Published: January 2020

The frequency of extreme weather events, including heat waves, is increasing with climate change. The thermoregulatory demands resulting from hotter weather can have catastrophic impacts on animals, leading to mass mortalities. Although less dramatic, animals also experience physiological costs below, but approaching, critical temperature thresholds. These costs may be particularly constraining during reproduction, when parents must balance thermoregulation against breeding activities. Such challenges should be acute among seabirds, which often nest in locations exposed to high solar radiation and predation risk. The globally endangered bank cormorant Phalacrocorax neglectus breeds in southern Africa in the winter, giving little scope for poleward or phenological shifts in the face of increasing temperatures. Physiological studies of endangered species sensitive to human disturbance, like the bank cormorant, are challenging, because individuals cannot be captured for experimental research. Using a novel, non-invasive, videographic approach, we investigated the thermoregulatory responses of this seabird across a range of environmental temperatures at three nesting colonies. The time birds spent gular fluttering, a behaviour enhancing evaporative heat loss, increased with temperature. Crouching or standing birds spent considerably less time gular fluttering than birds sitting on nests (ca 30% less at 22°C), showing that postural adjustments mediate exposure to heat stress and enhance water conservation. Crouching or standing, however, increases the vulnerability of eggs and chicks to suboptimal temperatures and/or expose nest contents to predation, suggesting that parents may trade-off thermoregulatory demands against offspring survival. We modelled thermoregulatory responses under future climate scenarios and found that nest-bound bank cormorants will gular flutter almost continuously for several hours a day by 2100. The associated increase in water loss may lead to dehydration, forcing birds to prioritize survival over breeding, a trade-off that would ultimately deteriorate the conservation status of this species.
Prot2HG: a database of protein domains mapped to the human genome
Authors: Stanek David , Bis-Brewer Dana M , Saghira Cima , Danzi Matt C , Seeman Pavel , Lassuthova Petra , Zuchner Stephan
Published: January 2020

Genetic variation occurring within conserved functional protein domains warrants special attention when examining DNA variation in the context of disease causation. Here we introduce a resource, freely available at www.prot2hg.com, that addresses the question of whether a particular variant falls onto an annotated protein domain and directly translates chromosomal coordinates onto protein residues. The tool can perform a multiple-site query in a simple way, and the whole dataset is available for download as well as incorporated into our own accessible pipeline. To create this resource, National Center for Biotechnology Information protein data were retrieved using the Entrez Programming Utilities. After processing all human protein domains, residue positions were reverse translated and mapped to the reference genome hg19 and stored in a MySQL database. In total, 760 487 protein domains from 42 371 protein models were mapped to hg19 coordinates and made publicly available for search or download (www.prot2hg.com). In addition, this annotation was implemented into the genomics research platform GENESIS in order to query nearly 8000 exomes and genomes of families with rare Mendelian disorders (tgp-foundation.org). When applied to patient genetic data, we found that rare (<1%) variants in the Genome Aggregation Database were significantly more annotated onto a protein domain in comparison to common (>1%) variants. Similarly, variants described as pathogenic or likely pathogenic in ClinVar were more likely to be annotated onto a domain. In addition, we tested a dataset consisting of 60 causal variants in a cohort of patients with epileptic encephalopathy and found that 71% of them (43 variants) were propagated onto protein domains. In summary, we developed a resource that annotates variants in the coding part of the genome onto conserved protein domains in order to increase variant prioritization efficiency.

Database URL: www.prot2hg.com
European citizens’ perspectives on direct-to-consumer genetic testing: an updated systematic review
Authors: Hoxhaj Ilda , Stojanovic Jovana , Boccia Stefania
Published: January 2020

Background

Direct-to-consumer genetic tests (DTC-GTs) are genetic tests for a medical or non-medical trait that are sold directly to the public, usually ordered without the engagement of a healthcare professional. Our aim was to explore the knowledge, attitudes and behaviors toward DTC-GTs among European citizens.

Methods

We updated the most recent systematic review on citizens’ perspectives toward DTC-GTs. Relevant English language studies were searched on PubMed, ISI Web of Science, Scopus, Embase and Google Scholar from October 2014 to April 2019. We extended our search on Scopus without publication date restriction, since it was not included in the former review. Eligible studies were conducted in European countries and reported original data. The quality of the studies was evaluated using a checklist developed by Kmet et al.

Results

We included six studies conducted in European countries between 2015 and 2018. The studies were performed among general population in the Netherlands, students in Italy and Greece, laypeople in Germany and older adults in Switzerland. The level of awareness, in overall low, differed by country and population group. Most of the participants were interested in undergoing a DTC-GT, mainly for knowing the risk predisposition to a common disease. Concerns were raised about tests’ validity and utility and data privacy.

Conclusions

Our review shows that European citizens, overall, have a low level of knowledge on DTC-GTs and a high interest in their purchase. This understanding might contribute to the development of educational programs in order to the increase of general public capabilities to make appropriate health decisions.
Emphasizing iterative practices for a sequential course-based undergraduate research experience in microbial biofilms
Authors: Light Caitlin J , Fegley Megan , Stamp Nancy
Published: January 2020

Iteration is a fundamental area of course design in course-based undergraduate research experiences (CUREs). Iteration includes development of many skills necessary for laboratory work, experimental design, data analysis, communication and teamwork. With a focus on the microbial biofilm research track of the First-year Research Immersion (FRI) program, the perceptions of four student cohorts were examined at the end of the three-term CURE sequence, relative to exposure to iterative tasks, learning gains and benefits from the research experience. Based on results from the first two cohorts, substantial changes were made in the CURE sequence to increase iterative tasks and discussion with students about the iterative nature of research. In turn, the results for the latter cohorts reached FRI program targets. In sum, novice researchers benefit from a deliberate step-wise approach for developing skills to meet the requirements and understand the complex role of iteration in real research.
Effect of betaine and selenium on the growth and photosynthetic pigment production in Dunaliella salina as biostimulants
Authors: Constantinescu-Aruxandei Diana , Vlaicu Alexandru , Marinaș Ioana Cristina , Vintilă Alin Cristian Nicolae , Dimitriu Luminița , Oancea Florin
Published: January 2020

The aim of our study was to establish the effect of selenium and betaine on the growth of D. salina, accumulation of photosynthetic pigments and antioxidant activity of the hydrophobic fraction. This approach was an attempt to demonstrate ‘microalgae biostimulant’ effects, similar to ‘plant biostimulant’ effects, i.e. increased tolerance to abiotic stress and enhanced accumulation of bioactive compounds. A high-throughput assay was done in 24-well microplates, at 15% NaCl and different concentrations of sodium selenite (0, 0.5, 2 and 8 µM) or betaine (0, 5, 50 and 500 µM). Both selenium and betaine induced a slight delay in algae growth during the actively growing stage but the final density reached similar values to the control. Betaine significantly enhanced (50%–100%) carotenoids and chlorophyll a accumulation, in a concentration depending manner. Antioxidant activity increased almost 3-fold in extracts of algae treated with 50 µM betaine. Selenium had a much more discrete effect than betaine on pigments biosynthesis. The antioxidant activity of the extracts increased 2-fold in the presence of Se compared to the control. Our work proves that it is possible to enhance production and activity of bioactive compounds from microalgae by using ingredients, which already proved to act as plant biostimulants.
Fertilization of Norway spruce forest with wood ash and nitrogen affected both tree growth and composition of chemical defence
Authors: Hanssen Kjersti Holt , Asplund Johan , Clarke Nicholas , Selmer Ruben , Nybakken Line
Published: January 2020

We fertilized a Norway spruce (Picea abies (L.) Karst.) stand on rich mineral soil with 3 t ha−1 of wood ash (ASH), 150 kg ha−1 of nitrogen (N) or a combination of wood ash and nitrogen (ASH + N), in addition to unfertilized control plots. After five growing seasons, we remeasured the trees and took core samples. Current- and previous-year needles were sampled and analyzed for total nitrogen and carbon, low-molecular weight phenolics and condensed tannins. Annual volume increment and standing volume were significantly higher in the ASH + N treatment than in control plots after 5 years. N gave a significant positive effect on basal area growth in the third year, after which the effect diminished. The ASH + N treated trees, on the other hand, showed an increasing basal area growth trend throughout the period. ASH reduced the total concentration of low-molecular weight phenolic compounds significantly in current-year needles. Phenolic acids increased under both ASH and ASH + N, while flavonoids decreased significantly under the same treatments compared to N. By including annual growth rate before fertilization in the analyses, the effect of N-treatment on flavonoids was positive only in trees with higher growth rates, and in those trees the concentration was higher than in both ASH-treated plots and controls. An acetophenone, constituting more than half of the total low-molecular weight phenolics concentration, was strongly reduced under all fertilization treatments. These results demonstrate that in addition to effects on tree growth, fertilization of the forest floor also has a strong influence on other metabolic processes of trees, with potential implications for ecosystem functioning.
Differential Expression in Testis and Liver Transcriptomes from Four Species of Peromyscus (Rodentia: Cricetidae)
Authors: Lindsey Laramie L , Platt Roy N , Phillips Caleb D , Ray David A , Bradley Robert D
Published: January 2020

The genus Peromyscus represents a rapidly diverged clade of Cricetid rodents that contains multiple cryptic species and has a propensity for morphologic conservation across its members. The unresolved relationships in previously proposed phylogenies reflect a suspected rapid adaptive radiation. To identify functional groups of genes that may be important in reproductive isolation in a reoccurring fashion across the Peromyscus phylogeny, liver and testis transcriptomes from four species (P. attwateri, P. boylii, P. leucopus, and P. maniculatus) were generated and differential expression (DE) tests were conducted. Taxa were selected to represent members diverged from a common ancestor: P. attwateri + P. boylii (clade A), and P. leucopus + P. maniculatus (clade B). Comparison of clades (A vs. B) suggested that 252 transcripts had significant DE in the liver data set, whereas significant DE was identified for 657 transcripts in the testis data set. Further, 45 genes had DE isoforms in the 657 testis transcripts and most of these functioned in major reproductive roles such as acrosome assembly, spermatogenesis, and cell cycle processes (meiosis). DE transcripts in the liver mapped to more broad gene ontology terms (metabolic processes, catabolic processes, response to chemical, and regulatory processes), and DE transcripts in the testis mapped to gene ontology terms associated with reproductive processes, such as meiosis, sperm motility, acrosome assembly, and sperm–egg fusion. These results suggest that a suite of genes that conduct similar functions in the testes may be responsible for the adaptive radiation events and potential reoccurring speciation of Peromyscus in terms of reproduction through varying expression levels.
Bring Back the Rat!
Authors: Carter Christy S , Richardson Arlan , Huffman Derek M , Austad Steven
Published: January 2020

As 2020 is “The Year of the Rat” in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging.
Genome and population sequencing of a chromosome-level genome assembly of the Chinese tapertail anchovy (Coilia nasus) provides novel insights into migratory adaptation
Authors: Xu Gangchun , Bian Chao , Nie Zhijuan , Li Jia , Wang Yuyu , Xu Dongpo , You Xinxin , Liu Hongbo , Gao Jiancao , Li Hongxia , Liu Kai , Yang Jian , Li Quanjie , Shao Nailin , Zhuang Yanbing , Fang Dian , Jiang Tao , Lv Yunyun , Huang Yu , Gu Ruobo , Xu Junmin , Ge Wei , Shi Qiong , Xu Pao
Published: January 2020

Background

Seasonal migration is one of the most spectacular events in nature; however, the molecular mechanisms related to this phenomenon have not been investigated in detail. The Chinese tapertail, or Japanese grenadier anchovy, Coilia nasus, is a valuable migratory fish of high economic importance and special migratory dimorphism (with certain individuals as non-migratory residents).

Results

In this study, an 870.0-Mb high-quality genome was assembled by the combination of Illumina and Pacific Biosciences sequencing. Approximately 812.1 Mb of scaffolds were linked to 24 chromosomes using a high-density genetic map from a family of 104 full siblings and their parents. In addition, population sequencing of 96 representative individuals from diverse areas along the putative migration path identified 150 candidate genes, which are mainly enriched in 3 Ca2+-related pathways. Based on integrative genomic and transcriptomic analyses, we determined that the 3 Ca2+-related pathways are critical for promotion of migratory adaption. A large number of molecular markers were also identified, which distinguished migratory individuals and non-migratory freshwater residents.

Conclusions

We assembled a chromosome-level genome for the Chinese tapertail anchovy. The genome provided a valuable genetic resource for understanding of migratory adaption and population genetics and will benefit the aquaculture and management of this economically important fish.
Incidence and Predictors of Flares in the Postpartum Year Among Women With Inflammatory Bowel Disease
Authors: Yu Amy , Friedman Sonia , Ananthakrishnan Ashwin N
Published: January 2020

Background

The postpartum period is marked by physiological and psychological stresses that may impact activity in inflammatory bowel disease. The predictors and outcomes of disease activity during this period have not been well characterized.

Methods

We performed a retrospective review of inflammatory bowel disease patients who underwent successful pregnancy and live birth at 2 referral institutions. Data on patient and disease factors including disease activity before and during pregnancy were abstracted from the medical records. We noted whether therapy was dose-reduced or stopped during pregnancy at each trimester and after delivery. Multivariable logistic regression of independent predictors of postpartum flare was performed, adjusting for relevant covariates.

Results

We identified a total of 206 eligible women (mean age, 33.2 years). Of these, 97 (47%) had a diagnosis of Crohn’s disease, whereas the remainder had ulcerative colitis. Nearly half the women delivered vaginally (53%), and the rest delivered by Caesarean section (47%). In the entire cohort, 65 (31.6%) experienced a postpartum flare within the year after delivery. In multivariable analysis, development of a postpartum flare was predicted by disease activity during the third trimester (odds ratio [OR], 6.27; 95% confidence interval [CI], 2.81–17.27), therapy de-escalation during pregnancy (OR, 3.00; 95% CI, 1.03–8.68), and therapy de-escalation after pregnancy (OR, 4.43; 95% CI, 1.55–12.65). Postpartum disease flare was not related to disease type, duration of disease, or mode of childbirth.

Conclusions

One-third of women with inflammatory bowel disease may experience disease flare during the postpartum year. Continued optimization of therapy before, during, and after pregnancy is essential to prevent this morbidity.
First indications for reduced mortality of non-target invertebrate benthic megafauna after pulse beam trawling
Authors: Bergman Magda J N , Meesters Erik H
Published: January 2020

Two alternative stimulation techniques to reduce mortality in benthic megafauna were tested relative to standard tickler chain beam trawling: longitudinal electrodes (pulse trawl) and longitudinal chains. Longitudinal chains caused higher mortality than pulse trawling in 3 species. Standard trawling gave higher mortality in Echinocardium cordatum than pulse trawling. Between longitudinal chain and standard trawling were no significant differences. This trend in decreasing mortality from longitudinal, to standard and then pulse trawling was confirmed by a similar decline in: i) numbers of significant species mortalities per trawl type, ii) average mortalities, i.e. longitudinal chain caused 41% more mortality than standard trawling and pulse trawling 43% less, iii) pre- and post-trawling community dissimilarities. A significant majority of species showed higher mortalities after longitudinal than after standard trawling and, conversely, lower mortalities after pulse trawling. Trawls with longitudinal chains instead of cross tickler chains increase megafaunal impact. On the contrary, pulse trawling can reduce the impact, although average mortality remains substantial (25%) even in impoverished benthic test assemblages in the southern North Sea. Power, generally was low and reference areas, free of (pulse) trawling, and inhabited by more vulnerable taxa will facilitate higher powered studies on the impact of standard and alternative trawling techniques.
An integrated investigation of the effects of ocean acidification on adult abalone (Haliotis tuberculata)
Authors: Avignon Solène , Auzoux-Bordenave Stéphanie , Martin Sophie , Dubois Philippe , Badou Aïcha , Coheleach Manon , Richard Nicolas , Di Giglio Sarah , Malet Loïc , Servili Arianna , Gaillard Fanny , Huchette Sylvain , Roussel Sabine
Published: January 2020

Ocean acidification (OA) and its subsequent changes in seawater carbonate chemistry are threatening the survival of calcifying organisms. Due to their use of calcium carbonate to build their shells, marine molluscs are particularly vulnerable. This study investigated the effect of CO2-induced OA on adult European abalone (Haliotis tuberculata) using a multi-parameter approach. Biological (survival, growth), physiological (pHT of haemolymph, phagocytosis, metabolism, gene expression), and structural responses (shell strength, nano-indentation measurements, Scanning electron microscopy imaging of microstructure) were evaluated throughout a 5-month exposure to ambient (8.0) and low (7.7) pH conditions. During the first 2 months, the haemolymph pH was reduced, indicating that abalone do not compensate for the pH decrease of their internal fluid. Overall metabolism and immune status were not affected, suggesting that abalone maintain their vital functions when facing OA. However, after 4 months of exposure, adverse effects on shell growth, calcification, microstructure, and resistance were highlighted, whereas the haemolymph pH was compensated. Significant reduction in shell mechanical properties was revealed at pH 7.7, suggesting that OA altered the biomineral architecture leading to a more fragile shell. It is concluded that under lower pH, abalone metabolism is maintained at a cost to growth and shell integrity. This may impact both abalone ecology and aquaculture.
The surgical management of retrograde type A aortic dissection after thoracic endovascular aortic repair
Authors: Dun Yaojun , Shi Yi , Guo Hongwei , Liu Yanxiang , Zhang Bowen , Sun Xiaogang , Qian Xiangyang , Yu Cuntao
Published: January 2020

OBJECTIVES

Our goal was to review the surgical treatment of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) in our centre.

METHODS

From January 2014 to April 2018, 22 patients with RTAD after TEVAR were operated on in our centre. The mean age at operation was 52.0 ± 8.0 years old. The median interval between the primary TEVAR procedure and RTAD was 4.6 months (range 0–120 months). The postoperative mortality and morbidity rates were calculated to evaluate the early and long-term results.

RESULTS

Twenty patients received total arch replacement with the frozen elephant trunk technique and 2 patients received total arch replacement alone. The mean cardiopulmonary bypass time, aortic cross-clamp time and selective cerebral perfusion time were 172.4 ± 39.3, 100.1 ± 30.3 and 19.7 ± 10.5 min, respectively. The incidence of major adverse events was 18.6% (4/22), including stroke in 1 patient, myocardial dysfunction in 1 patient and renal failure necessitating dialysis in 3 patients. Death within 30 days was 13.6% (3/22 patients). The follow-up data were available for all 19 survivors. The mean follow-up period was 32.2 ± 16.2 months (range 10–62 months). No deaths or aortic-related events occurred during the follow-up period.

CONCLUSIONS

Total arch replacement with or without the frozen elephant trunk technique was suitable for the management of RTAD after TEVAR, with acceptable early and long-term results.
The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?
Authors: Leonard Michael Z , Rostin Paul , Hill Kevin P , Grabitz Stephanie D , Eikermann Matthias , Miczek Klaus A
Published: January 2020

Background

Reexposure to methamphetamine with a single “priming dose” can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril “molecular container” calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats.

Methods

Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2.

Results

Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine.

Conclusions

These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.
A Basis of Casimirs in 3D Magnetohydrodynamics
Authors: Khesin Boris , Peralta-Salas Daniel , Yang Cheng
Published: January 2020

We prove that any regular Casimir in 3D magnetohydrodynamics (MHD) is a function of the magnetic helicity and cross-helicity. In other words, these two helicities are the only independent regular integral invariants of the coadjoint action of the MHD group $\textrm{SDiff}(M)\ltimes \mathfrak X^*(M)$, which is the semidirect product of the group of volume-preserving diffeomorphisms and the dual space of its Lie algebra.
Effect of high-dose rifampicin on efavirenz pharmacokinetics: drug–drug interaction randomized trial
Authors: Atwine Daniel , Baudin Elisabeth , Gelé Thibaut , Muyindike Winnie , Mworozi Kenneth , Kyohairwe Racheal , Kananura Keneth , Orikiriza Patrick , Nyehangane Dan , K.T. Nanjebe Deborah , Furlan Valérie , Verstuyft Céline , Barrail-Tran Aurélie , Taburet Anne-Marie , Bonnet Maryline ,   ANRS 12292 Rifavirenz study group, Logoose S , Akatuhebwa D , Asiimwe B , Arimpa A , Arinaitwe R , Mwanga-Amumpaire J , Taremwa I M , Mucunguzi E , Kyarimpa R , Muganzi D , Natukunda E , Atwine L , Kassaza K , Turyashemererwa E , Munyambabazi H , Nalusaji A , Turuho T , Tumwebaze B , Bertrand J , Rouveau N , Justumus P
Published: January 2020

Background

High-dose rifampicin is considered to shorten anti-TB treatment duration but its effect on antiretroviral metabolism is unknown.

Objectives

To assess the effect of doubling the rifampicin dose (to 20 mg/kg/day, R20) on efavirenz pharmacokinetics (PK) in HIV/TB coinfected patients.

Methods

Open-label Phase 2 drug–drug interaction randomized trial. Pulmonary TB, ART-naive adults were randomized to R20 and either efavirenz 600 mg (EFV600) or 800 mg (EFV800), or rifampicin 10 mg/kg/day (R10) and EFV600 with a 1:1:1 ratio. Patients were first started on TB treatment and 2–4 weeks later started on ART. They were switched to R10 and EFV600 after 8 weeks. Full PK sampling was done 4 weeks (on rifampicin) and 24 weeks (off rifampicin) after ART initiation. Transaminases, plasma HIV-1 RNA and sputum cultures were monitored. The efavirenz geometric mean ratio (GMR) of AUC at 4 and 24 weeks after ART initiation within the same patient was calculated in each arm and its 90% CI was compared with a preset range (0.70–1.43).

Results

Of 98 enrolled patients (32 in the R20EFV600 arm, 33 in the R20EFV800 arm and 33 in the R10EFV600 arm), 87 had full PK sampling. For the R20EFV600, R20EFV800 and R10EFV600 arms, GMRs of efavirenz AUC were 0.87 (90% CI: 0.75–1.00), 1.12 (90% CI: 0.96–1.30) and 0.96 (90% CI: 0.84–1.10). Twelve weeks after ART initiation, 78.6%, 77.4% and 72.4% of patients had HIV-1 RNA below 100 copies/mL and 85.7%, 86.7% and 80.0% had Week 8 culture conversion, respectively. Two patients per arm experienced a severe increase in transaminases.

Conclusions

Doubling the rifampicin dose had a small effect on efavirenz concentrations and was well tolerated.
A Novel Cell-Free Fluorescent Assay for HDL Function: Low Apolipoprotein A1 Exchange Rate Associated with Increased Incident Cardiovascular Events
Authors: Lorkowski Shuhui Wang , Brubaker Gregory , Li Lin , Li Xinmin S , Hazen Stanley L , Smith Jonathan D
Published: January 2020

Background

Cholesterol efflux capacity is a tissue culture assay for HDL function that is not amenable for high-throughput monitoring of risk assessment.

Methods

We devised a cell-free HDL function assay to measure the exchange rate of exogenous apoA1 into serum HDL using NBD/Alexa647 double-labeled apoA1, whose NBD/Alexa647 emission ratio increased upon exchange into HDL. ApoA1 exchange rate (AER) was assayed by incubating labeled apoA1 with human serum, and the rate of the increase of the NBD/Alexa647 ratio over time was calculated as AER.

Results

Fast protein liquid chromatography analysis of serum confirmed that the labeled apoA1 selectively exchanged into the HDL lipoprotein fraction. Characterization studies demonstrated that the AER assay had excellent intra- and inter-day reproducibility, was stable over 3 freeze-thaw cycles, and yielded similar results with serum or plasma. We quantified AER in serum from randomly selected stable subjects undergoing elective diagnostic coronary angiography (n = 997). AER was correlated with HDL-cholesterol (r = 0.58, P < 0.0001) and apoA1 levels (r = 0.56, P < 0.0001). Kaplan-Meier survival plot showed subjects in the lowest quartile of AER experienced a significantly higher rate of incident major adverse cardiovascular events (MACE = myocardial infarction, stroke, or death) (P < 0.0069 log rank). Moreover, compared to subjects in the lowest AER quartile, the remaining subjects showed significantly lower incident (3 year) risk for MACE, even after adjustment for traditional risk factors and apoA1 (HR 0.58; 95% CI 0.40–0.85; P = 0.005).

Conclusions

In a prospective cohort of stable subjects undergoing elective diagnostic cardiac evaluations, low AER was associated with increased incident risk of MACE.
A Single-Column Gas Chromatography Method for Quantifying Toxic Alcohols
Authors: Kemble David J , Cervinski Mark A
Published: January 2020

Background

Rapid identification and quantification of toxic alcohols and ethylene glycol is imperative for appropriate treatment. Clinical laboratories frequently rely on direct injection gas chromatography (GC) methods, but these methods require inlet maintenance and multiple GC systems. To overcome these challenges, we developed a single-column headspace GC method for both toxic alcohols and glycols that streamlines patient sample analysis for toxic alcohol ingestion.

Methods

Optimal parameters for nonderivatized (volatile) and derivatized (glycol) plasma samples were determined using a 7890 A headspace sampler, an Agilent 7697 A GC system, a DB-200 column, and a flame ionization detector. Limit of Quantification (LoQ), linearity, imprecision, carry-over, method comparison, and interference studies were performed using quality control materials and prepared plasma samples.

Results

Our volatile method is linear to 3000 mg/L (ethanol) with LoQ concentrations below 20 mg/L (ethanol). The glycol method is linear to 2000 mg/L (ethylene glycol) with LoQ concentrations below 40 mg/L (ethylene glycol). Total assay impression ranged from 1.7% for ethanol to 13.3% for propylene glycol. Both methods were free of sample carryover and compared favorably with a similar clinical method at an outside laboratory. Propionic acid, an accumulating metabolite in methylmalonic acidemia that interferes with ethylene glycol identification by a different method, did not interfere with the ethylene glycol method reported here.

Conclusions

Our single-column headspace GC method provides reliable, robust, and rapid identification and quantification of commonly encountered toxic alcohols. Clinical laboratories relying on direct injection Gas Chromatography (GC) for toxic alcohol analysis face challenges including frequent inlet maintenance, sample carryover, or the need for separate GC systems for volatile and glycol analysis. We summarize our development and optimization of two headspace GC methods for nonderivatized (volatile) and derivatized (glycol) plasma samples that use a single DB-200 analytical column. These methods are comparable to other GC methods, not prone to sample carryover, eliminate the need for multiple GC systems or columns, and are readily applicable to other laboratories that provide toxic alcohol analysis.
The Impact of Undetected In Vitro Hemolysis or Sample Contamination on Patient Care and Outcomes in Point-of-Care Testing: A Retrospective Study
Authors: O’Hara Matthew , Wheatley Elizabeth G , Kazmierczak Steven C
Published: January 2020

Background

Point-of-care (POC) testing is an integral diagnostic component in clinical settings like the emergency department (ED). However, most POC testing devices are unable to detect endogenous interferents such as hemolysis, which typically occurs during sample collection and handling and can falsely increase measured potassium (pseudohyperkalemia), a phenomenon we hypothesized may significantly impact patient care.

Methods

In this retrospective study, we evaluated 100 unique admissions to the Oregon Health & Science University ED, presenting with elevated potassium measured at the POC. To evaluate whether in vitro hemolysis had occurred, POC test results were compared to repeat testing of the original specimen, or other specimens tested within 90 minutes in the Core laboratory. Review of associated Electronic Health Records determined whether elevated potassium initially measured using the POC analyzer was real, or due to in vitro hemolysis or contamination, and whether pseudohyperkalemia impacted patient management or care.

Results

Of the 100 admissions with hyperkalemia measured using a POC analyzer, 40% were found to have pseudohyperkalemia due to hemolysis or contamination. Of these 40 patients, 6 experienced repeated testing, and an additional 5 were noted to have altered patient management, specifically due to pseudohyperkalemia.

Conclusions

This study demonstrates the incidence of in vitro hemolysis, which is unknown to the POC operator, is high in patients who show an elevated potassium as measured at the POC. Furthermore, in vitro hemolysis can significantly impact patient management, suggesting that minimizing the incidence of unrecognized hemolysis will benefit hospital efficiency, decrease waste, and improve patient care.