bluuebunny/crossref_metadata_2025_split huggingface dataset:
A compositional mediation model for a binary outcome: Application to microbiome studies
Authors: Sohn Michael B , Lu Jiarui , Li Hongzhe 
Published: August 2021

AbstractMotivationThe delicate balance of the microbiome is implicated in our health and is shaped by external factors, such as diet and xenobiotics. Therefore, understanding the role of the microbiome in linking external factors and our health conditions is crucial to translate microbiome research into therapeutic and preventative applications.ResultsWe introduced a sparse compositional mediation model for binary outcomes to estimate and test the mediation effects of the microbiome utilizing the compositional algebra defined in the simplex space and a linear zero-sum constraint on probit regression coefficients. For this model with the standard causal assumptions, we showed that both the causal direct and indirect effects are identifiable. We further developed a method for sensitivity analysis for the assumption of the no unmeasured confounding effects between the mediator and the outcome. We conducted extensive simulation studies to assess the performance of the proposed method and applied it to real microbiome data to study mediation effects of the microbiome on linking fat intake to overweight/obesity.Availability and implementationAn R package can be downloaded from https://github.com/mbsohn/cmmb.Supplementary informationSupplementary files are available at Bioinformatics online.
Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity
Authors: Liebmann Marie , Korn Lisanne , Janoschka Claudia , Albrecht Stefanie , Lauks Sarah , Herrmann Alexander M , Schulte-Mecklenbeck Andreas , Schwab Nicholas , Schneider-Hohendorf Tilman , Eveslage Maria , Wildemann Brigitte , Luessi Felix , Schmidt Stephan , Diebold Martin , Bittner Stefan , Gross Catharina C , Kovac Stjepana , Zipp Frauke , Derfuss Tobias , Kuhlmann Tanja , König Simone , Meuth Sven G , Wiendl Heinz , Klotz Luisa 
Published: August 2021

Abstract
Dimethyl fumarate, an approved treatment for relapsing-remitting multiple sclerosis, exerts pleiotropic effects on immune cells as well as CNS resident cells.
Here, we show that dimethyl fumarate exerts a profound alteration of the metabolic profile of human CD4+ as well as CD8+ T cells and restricts their antioxidative capacities by decreasing intracellular levels of the reactive oxygen species scavenger glutathione. This causes an increase in mitochondrial reactive oxygen species levels accompanied by an enhanced mitochondrial stress response, ultimately leading to impaired mitochondrial function. Enhanced mitochondrial reactive oxygen species levels not only result in enhanced T-cell apoptosis in vitro as well as in dimethyl fumarate-treated patients, but are key for the well-known immunomodulatory effects of dimethyl fumarate both in vitro and in an animal model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis. Indeed, dimethyl fumarate immune-modulatory effects on T cells were completely abrogated by pharmacological interference of mitochondrial reactive oxygen species production.
These data shed new light on dimethyl fumarate as bona fide immune-metabolic drug that targets the intracellular stress response in activated T cells, thereby restricting mitochondrial function and energetic capacity, providing novel insight into the role of oxidative stress in modulating cellular immune responses and T cell-mediated autoimmunity.
Physiological response and survival of Atlantic mackerel exposed to simulated purse seine crowding and release
Authors: Anders Neil , Roth Bjørn , Breen Mike 
Published: August 2021

AbstractUnderstanding how animals physiologically respond to capture and release from wild capture fishing is fundamental for developing practices that enhance their welfare and survival. As part of purse seine fishing for small pelagic fish in northern European waters, excess and/or unwanted catches are routinely released from the net in a process called slipping. Due to excessive crowding in the net prior to release, post-slipping mortality rates can be unacceptably high. Atlantic mackerel (Scomber scombrus) support large and economically important purse seine fisheries but are known to be particularly vulnerable to such crowding-induced mortality. Developing management advice to promote post-slipping survival for this species is currently challenging, due to a lack of understanding of how crowding influences their physiology. Here we examine the physiological response, recovery and survival of wild caught mackerel exposed to various degrees and durations of simulated crowding stress in a series of sea cage trials. The magnitude of the physiological response and its time to recovery was positively correlated with crowding density and duration and was characterized by cortisol elevation, energy mobilization and anaerobic metabolite accumulation. There were also indications of osmoregulatory disturbance. Skin injury and mortality rates showed a similar positive relationship to crowding density. The physiological disturbance was recoverable for most fish. Instead, the rate at which mortalities developed and the physiological profile of moribund fish indicated that skin injury, likely arising from abrasive contact with netting and other fish during crowding, was the probable cause of mortality. Injured fish also exhibited a loss of allometric condition relative to non-injured survivors. Crowding treatments were potentially confounded by differences in ambient oxygen reduction, water temperature and pre-treatment fish condition between trials, and densities were replicated only once. These results contribute to the development of welfare conscious fishing practices that aim to reduce post-slipping mortality.
Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes
Authors: Luo Hao , Lan Cong , Fan Chao , Gong Xue , Chen Caiyu , Yu Cheng , Wang Jialiang , Luo Xiaoli , Hu Cuimei , Jose Pedro A , Xu Zaicheng , Zeng Chunyu 
Published: August 2021

Abstract

Aims
Exposure to maternal diabetes is associated with increased prevalence of hypertension in the offspring. The mechanisms underlying the prenatal programming of hypertension remain unclear. Because endoplasmic reticulum (ER) stress plays a key role in vascular endothelial dysfunction in hypertension, we investigated whether aberrant ER stress causes endothelial dysfunction and high blood pressure in the offspring of dams with diabetes.

Methods and results
Pregnant Sprague-Dawley rats were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at Day 0 of gestation. Compared with control mother offspring (CMO), the diabetic mother offspring (DMO) had higher blood pressure and impaired endothelium-dependent relaxation in mesenteric arteries, accompanied by decreased AMPK phosphorylation and PPARδ expression, increased ER stress markers, and reactive oxygen species (ROS) levels. The inhibition of ER stress reversed these aberrant changes in DMO. Ex vivo treatment of mesenteric arteries with an AMPK agonist (A769662) or a PPARδ agonist (GW1516) improved the impaired EDR in DMO and reversed the tunicamycin-induced ER stress, ROS production, and EDR impairment in mesenteric arteries from CMO. The effects of A769662 were abolished by co-treatment with GSK0660 (PPARδ antagonist), whereas the effects of GW1516 were unaffected by Compound C (AMPK inhibitor).

Conclusion
These results suggest an abnormal foetal programming of vascular endothelial function in offspring of rats with maternal diabetes that is associated with increased ER stress, which can be ascribed to down-regulation of AMPK/PPARδ signalling cascade.
A patient with pulmonary embolism takes a surprising HIT: a case report
Authors: Wasserstrum Yishay , Lubetzky Aaron , Goitein Orly , Matetzky Shlomo 
Published: August 2021

Abstract

Background
Venous thromboembolism (VTE) is a common condition that may manifest as intermediate or high-risk pulmonary embolism (PE), requiring either primary or subsequent fibrinolytic therapy. In these cases, catheter-directed thrombolysis (CDT) has been shown to be beneficial.

Case summary
We present the case of a borderline obese but otherwise healthy 43-year-old male individual, who was admitted with acute intermediate- to high-risk PE requiring treatment with intravenous unfractionated heparin. After initial therapy failure, the patient received CDT, with subsequent clinical worsening, and a mixed result of imaging studies suggesting partial central worsening and partial peripheral improvement of the thrombotic burden and right ventricular (RV) function. After a multidisciplinary PE response team (PERT) consultation, the diagnosis of heparin-induced thrombocytopenia (HIT) with normal platelet levels was made. Therapy was changed to intravenous bivalirudin, with an excellent clinical response and complete recovery of RV function. The patient was discharged with oral rivaroxaban therapy, and on follow-up was otherwise well.

Discussion
Apparent failure of thrombolytic therapy for VTE warrants a clinical investigation into possible causes of a pro-thrombotic state. In this case, the diagnosis of HIT was surprising, especially due to only a mild decline in platelet levels that were well within normal range. We also acknowledge the significance of our PERT in the key diagnosis made in this case.
Patient-reported outcomes, clinical, and demographic variables as predictors of withdrawal from the workforce after hospitalization with heart failure: findings from the national DenHeart survey
Authors: Tjustrup Nina Cecilie , Engel Schmidt Signe , Christensen Anne Vingaard , Rasmussen Trine Bernholdt , Borregaard Britt , Thrysoee Lars , Mols Rikke Elmose , Thorup Charlotte Brun , Juel Knud , Ankerstjerne Anne , Berg Selina Kikkenborg 
Published: August 2021

Abstract

Aims
Increased prevalence and survival among patients with heart failure draws attention to their everyday life, including their ability to work. Many patients with heart failure withdraw from the workforce, which can affect their quality of life. The aim was to investigate patient-reported outcomes (PROs) and clinical and demographic variables as predictors of withdrawal from the workforce after admission with a diagnose of heart failure.

Methods and results
Patients with heart failure, who were part of the workforce at admission were included from the national cross-sectional survey, DenHeart. Data were collected from five national heart centres in Denmark, from April 2013 to April 2014. Patient-reported outcomes measured at discharge included SF-12, HeartQoL, HADS, and ESAS. Clinical and demographic variables were obtained from registers, medical records, and index hospitalization. Patient-reported outcomes, clinical, and demographic variables were combined with labour market affiliation 3, 6, 9, and 12 months after admission. The response rate was 49.1% (n = 1517) and of those 364 patients were part of the workforce at index admission. Patients with lower QoL odds ratio (OR) 2.58 [95% confidence interval (CI) 1.24–5.37], symptoms of depression OR 2.57 (95% CI 1.47–4.50) and ejection fraction (EF) ≤35% OR 2.48 (95% CI 1.35–4.56) were more likely to withdraw from the workforce in the first year after admission. Patients with lower symptom burden OR 0.36 (95% CI 0.19–0.68) and a hospital stay of 0–2 days OR 0.18(95% CI 0.08–0.37) were less likely to withdraw.

Conclusion
Low QoL, high symptom burden, symptoms of depression, a longer length of hospital stay, and low EF can predict withdrawal from the workforce in the first year after admission with heart failure.
Genomic and molecular evidence reveals novel pathways associated with cell surface polysaccharides in bacteria
Authors: Simunović Vesna 
Published: August 2021

ABSTRACT
Amino acid (acyl carrier protein) ligases (AALs) are a relatively new family of bacterial amino acid adenylating enzymes with unknown function(s). Here, genomic enzymology tools that employ sequence similarity networks and genome context analyses were used to hypothesize the metabolic function(s) of AALs. In over 50% of species, aal and its cognate acyl carrier protein (acp) genes, along with three more genes, formed a highly conserved AAL cassette. AAL cassettes were strongly associated with surface polysaccharide gene clusters in Proteobacteria and Actinobacteria, yet were prevalent among soil and rhizosphere-associated α- and β-Proteobacteria, including symbiotic α- and β-rhizobia and some Mycolata. Based on these associations, AAL cassettes were proposed to encode a noncanonical Acp-dependent polysaccharide modification route. Genomic-inferred predictions were substantiated by published experimental evidence, revealing a role for AAL cassettes in biosynthesis of biofilm-forming exopolysaccharide in pathogenic Burkholderia and expression of aal and acp genes in nitrogen-fixing Rhizobium bacteroids. Aal and acp genes were associated with dltBD-like homologs that modify cell wall teichoic acids with d-alanine, including in Paenibacillus and certain other bacteria. Characterization of pathways that involve AAL and Acp may lead to developing new plant and human disease-controlling agents as well as strains with improved nitrogen fixation capacity.
Global analysis of Saccharomyces cerevisiae growth in mucin
Authors: Mercurio Kevin , Singh Dylan , Walden Elizabeth , Baetz Kristin 
Published: August 2021

Abstract
Metagenomic profiling of the human gut microbiome has discovered DNA from dietary yeasts like Saccharomyces cerevisiae. However, it is unknown if the S. cerevisiae detected by common metagenomic methods are from dead dietary sources, or from live S. cerevisiae colonizing the gut similar to their close relative Candida albicans. While S. cerevisiae can adapt to minimal oxygen and acidic environments, it has not been explored whether this yeast can metabolize mucin, the large, gel-forming, highly glycosylated proteins representing a major source of carbon in the gut mucosa. We reveal that S. cerevisiae can utilize mucin as their main carbon source, as well as perform both a transcriptome analysis and a chemogenomic screen to identify biological pathways required for this yeast to grow optimally in mucin. In total, 739 genes demonstrate significant differential expression in mucin culture, and deletion of 21 genes impact growth in mucin. Both screens suggest that mitochondrial function is required for proper growth in mucin, and through secondary assays we determine that mucin exposure induces mitogenesis and cellular respiration. We further show that deletion of an uncharacterized ORF, YCR095W-A, led to dysfunction in mitochondrial morphology and oxygen consumption in mucin. Finally, we demonstrate that Yps7, an aspartyl protease and homolog to mucin-degrading proteins in C. albicans, is important for growth on mucin. Collectively, our work serves as the initial step toward establishing how this common dietary fungus can survive in the mucus environment of the human gut.
Crafting for a better MAGIC: systematic design and test for Multiparental Advanced Generation Inter-Cross population
Authors: Yang Chin Jian , Edmondson Rodney N , Piepho Hans-Peter , Powell Wayne , Mackay Ian 
Published: August 2021

Abstract
Multiparental Advanced Generation Inter-Cross (MAGIC) populations are valuable crop resources with a wide array of research uses including genetic mapping of complex traits, management of genetic resources and breeding of new varieties. Multiple founders are crossed to create a rich mosaic of highly recombined founder genomes in the MAGIC recombinant inbred lines (RILs). Many variations of MAGIC population designs exist; however, a large proportion of the currently available populations have been created empirically and based on similar designs. In our evaluations of five MAGIC populations, we found that the choice of designs has a large impact on the recombination landscape in the RILs. The most popular design used in many MAGIC populations has been shown to have a bias in recombinant haplotypes and low level of unique recombinant haplotypes, and therefore is not recommended. To address this problem and provide a remedy for the future, we have developed the “magicdesign” R package for creating and testing any MAGIC population design via simulation. A Shiny app version of the package is available as well. Our “magicdesign” package provides a unifying tool and a framework for creativity and innovation in MAGIC population designs. For example, using this package, we demonstrate that MAGIC population designs can be found which are very effective in creating haplotype diversity without the requirement for very large crossing programs. Furthermore, we show that interspersing cycles of crossing with cycles of selfing is effective in increasing haplotype diversity. These approaches are applicable in species that are hard to cross or in which resources are limited.
RNAProt: an efficient and feature-rich RNA binding protein binding site predictor
Authors: Uhl Michael , Tran Van Dinh , Heyl Florian , Backofen Rolf 
Published: August 2021

Abstract

Background
Cross-linking and immunoprecipitation followed by next-generation sequencing (CLIP-seq) is the state-of-the-art technique used to experimentally determine transcriptome-wide binding sites of RNA-binding proteins (RBPs). However, it relies on gene expression, which can be highly variable between conditions and thus cannot provide a complete picture of the RBP binding landscape. This creates a demand for computational methods to predict missing binding sites. Although there exist various methods using traditional machine learning and lately also deep learning, we encountered several problems: many of these are not well documented or maintained, making them difficult to install and use, or are not even available. In addition, there can be efficiency issues, as well as little flexibility regarding options or supported features.

Results
Here, we present RNAProt, an efficient and feature-rich computational RBP binding site prediction framework based on recurrent neural networks. We compare RNAProt with 1 traditional machine learning approach and 2 deep-learning methods, demonstrating its state-of-the-art predictive performance and better run time efficiency. We further show that its implemented visualizations capture known binding preferences and thus can help to understand what is learned. Since RNAProt supports various additional features (including user-defined features, which no other tool offers), we also present their influence on benchmark set performance. Finally, we show the benefits of incorporating additional features, specifically structure information, when learning the binding sites of an hairpin loop binding RBP.

Conclusions
RNAProt provides a complete framework for RBP binding site predictions, from data set generation over model training to the evaluation of binding preferences and prediction. It offers state-of-the-art predictive performance, as well as superior run time efficiency, while at the same time supporting more features and input types than any other tool available so far. RNAProt is easy to install and use, comes with comprehensive documentation, and is accompanied by informative statistics and visualizations. All this makes RNAProt a valuable tool to apply in future RBP binding site research.
Exploring the potential of citizen science for public health through an alcohol advertising case study
Authors: Thomas Jessica A , Trigg Joshua , Morris Julia , Miller Emma , Ward Paul R 
Published: August 2021

Summary
Citizen science connects academic researchers with the public through combined efforts in scientific inquiry. The importance of involving impacted populations in health research is well established. However, how to achieve meaningful participation and the methodological impact of citizen science needs further examination. We examined the feasibility of using citizen science to understand the impact of alcohol advertising on Australian women through a breast cancer prevention project. Two hundred and eighty-two (‘participants’) citizen scientists completed demographic and behavioural questions via an online survey. The research participants moved into the role of citizen scientists by completing the data collection tasks of capturing and classifying images of alcohol advertising they saw online. Interrater reliability tests found high levels of agreement between citizen scientists and academic researchers with the classification of alcohol advertising brand (Kappa = 0.964, p &lt; 0.001) and image type (Kappa = 0.936, p &lt; 0.000). The citizen scientists were women aged 18 and over, with 62% between 35 and 55 years old. The majority were from major cities (78%), had attained a bachelor’s degree or higher-level education (62%) and were recruited via email or Facebook (86%). The use of citizen science provided methodological gains through the creation of a unique dataset with higher levels of validity than the existing literature, which employed traditional investigator-driven research methodologies. Citizen science enriched the dataset and provided a powerful methodological vehicle to understand an environmental determinant of health. The study illuminates how public participation benefitted the research process, the challenges and the potential for citizen science to improve public health.
TIDE Analysis of Cryptosporidium Infections by gp60 Typing Reveals Obscured Mixed Infections
Authors: Dettwiler Ines , Troell Karin , Robinson Guy , Chalmers Rachel M , Basso Walter , Rentería-Solís Zaida Melina , Daugschies Arwid , Mühlethaler Konrad , Dale Mariko I , Basapathi Raghavendra Jyothi , Ruf Marie-Thérèse , Poppert Sven , Meylan Mireille , Olias Philipp 
Published: August 2021

Abstract

Background
Cryptosporidiosis is a parasitic disease associated with potentially fatal diarrhea. The most used method in Cryptosporidium subtyping is based on the glycoprotein gene gp60. Each infection can represent a parasite population, and it is important to investigate the influence on transmission and virulence, as well as any impact on public health investigations. However, an easy-to-use method for detection is lacking.

Methods
Here we report on the use of the bioinformatic program TIDE for deconvolution of gp60 chromatograms. A combination of single oocyst analysis and cloning successfully confirmed the within-sample parasite population diversity. Retrospective sample analysis was conducted on archived chromatograms.

Results
For Cryptosporidium parvum, 8.6% multistrain infections (13 of 152) obscured by currently used consensus base calling were detected. Importantly, we show that single oocysts can harbor a mixed population of sporozoites. We also identified a striking dominance of unappreciated polymerase stutter artefacts in all 218 chromatograms analyzed, challenging the uncritical use of gp60 typing.

Conclusions
We demonstrate the value of a new, easy-to-use analytical procedure for critical characterization of C. parvum and Cryptosporidium hominis in epidemiological investigations, also applicable retrospectively. Our findings illuminate the hidden parasite diversity with important implications for tracing zoonotic and person-to-person transmissions.