bluuebunny/crossref_metadata_2025 huggingface dataset:
Few shot domain adaptation forin situmacromolecule structural classification in cryoelectron tomograms
Authors: Yu Liangyong , Li Ran , Zeng Xiangrui , Wang Hongyi , Jin Jie , Ge Yang , Jiang Rui , Xu Min
Published: July 2020

Motivation

Cryoelectron tomography (cryo-ET) visualizes structure and spatial organization of macromolecules and their interactions with other subcellular components inside single cells in the close-to-native state at submolecular resolution. Such information is critical for the accurate understanding of cellular processes. However, subtomogram classification remains one of the major challenges for the systematic recognition and recovery of the macromolecule structures in cryo-ET because of imaging limits and data quantity. Recently, deep learning has significantly improved the throughput and accuracy of large-scale subtomogram classification. However, often it is difficult to get enough high-quality annotated subtomogram data for supervised training due to the enormous expense of labeling. To tackle this problem, it is beneficial to utilize another already annotated dataset to assist the training process. However, due to the discrepancy of image intensity distribution between source domain and target domain, the model trained on subtomograms in source domain may perform poorly in predicting subtomogram classes in the target domain.

Results

In this article, we adapt a few shot domain adaptation method for deep learning-based cross-domain subtomogram classification. The essential idea of our method consists of two parts: (i) take full advantage of the distribution of plentiful unlabeled target domain data, and (ii) exploit the correlation between the whole source domain dataset and few labeled target domain data. Experiments conducted on simulated and real datasets show that our method achieves significant improvement on cross domain subtomogram classification compared with baseline methods.

Availability and implementation

Software is available online https://github.com/xulabs/aitom.

Supplementary information

Supplementary data are available at Bioinformatics online.
A statistical approach for tracking clonal dynamics in cancer using longitudinal next-generation sequencing data
Authors: Vavoulis Dimitrios V , Cutts Anthony , Taylor Jenny C , Schuh Anna
Published: July 2020

Motivation

Tumours are composed of distinct cancer cell populations (clones), which continuously adapt to their local micro-environment. Standard methods for clonal deconvolution seek to identify groups of mutations and estimate the prevalence of each group in the tumour, while considering its purity and copy number profile. These methods have been applied on cross-sectional data and on longitudinal data after discarding information on the timing of sample collection. Two key questions are how can we incorporate such information in our analyses and is there any benefit in doing so?

Results

We developed a clonal deconvolution method, which incorporates explicitly the temporal spacing of longitudinally sampled tumours. By merging a Dirichlet Process Mixture Model with Gaussian Process priors and using as input a sequence of several sparsely collected samples, our method can reconstruct the temporal profile of the abundance of any mutation cluster supported by the data as a continuous function of time. We benchmarked our method on whole genome, whole exome and targeted sequencing data from patients with chronic lymphocytic leukaemia, on liquid biopsy data from a patient with melanoma and on synthetic data and we found that incorporating information on the timing of tissue collection improves model performance, as long as data of sufficient volume and complexity are available for estimating free model parameters. Thus, our approach is particularly useful when collecting a relatively long sequence of tumour samples is feasible, as in liquid cancers (e.g. leukaemia) and liquid biopsies.

Availability and implementation

The statistical methodology presented in this paper is freely available at github.com/dvav/clonosGP.

Supplementary information

Supplementary data are available at Bioinformatics online.
Triplet-based similarity score for fully multilabeled trees with poly-occurring labels
Authors: Ciccolella Simone , Bernardini Giulia , Denti Luca , Bonizzoni Paola , Previtali Marco , Della Vedova Gianluca
Published: July 2020

Motivation

The latest advances in cancer sequencing, and the availability of a wide range of methods to infer the evolutionary history of tumors, have made it important to evaluate, reconcile and cluster different tumor phylogenies. Recently, several notions of distance or similarities have been proposed in the literature, but none of them has emerged as the golden standard. Moreover, none of the known similarity measures is able to manage mutations occurring multiple times in the tree, a circumstance often occurring in real cases.

Results

To overcome these limitations, in this article, we propose MP3, the first similarity measure for tumor phylogenies able to effectively manage cases where multiple mutations can occur at the same time and mutations can occur multiple times. Moreover, a comparison of MP3 with other measures shows that it is able to classify correctly similar and dissimilar trees, both on simulated and on real data.

Availability and implementation

An open source implementation of MP3 is publicly available at https://github.com/AlgoLab/mp3treesim.

Supplementary information

Supplementary data are available at Bioinformatics online.
Co-phosphorylation networks reveal subtype-specific signaling modules in breast cancer
Authors: Ayati Marzieh , Chance Mark R , Koyutürk Mehmet
Published: July 2020

Motivation

Protein phosphorylation is a ubiquitous mechanism of post-translational modification that plays a central role in cellular signaling. Phosphorylation is particularly important in the context of cancer, as downregulation of tumor suppressors and upregulation of oncogenes by the dysregulation of associated kinase and phosphatase networks are shown to have key roles in tumor growth and progression. Despite recent advances that enable large-scale monitoring of protein phosphorylation, these data are not fully incorporated into such computational tasks as phenotyping and subtyping of cancers.

Results

We develop a network-based algorithm, CoPPNet, to enable unsupervised subtyping of cancers using phosphorylation data. For this purpose, we integrate prior knowledge on evolutionary, structural and functional association of phosphosites, kinase–substrate associations and protein–protein interactions with the correlation of phosphorylation of phosphosites across different tumor samples (a.k.a co-phosphorylation) to construct a context-specific-weighted network of phosphosites. We then mine these networks to identify subnetworks with correlated phosphorylation patterns. We apply the proposed framework to two mass-spectrometry-based phosphorylation datasets for breast cancer (BC), and observe that (i) the phosphorylation pattern of the identified subnetworks are highly correlated with clinically identified subtypes, and (ii) the identified subnetworks are highly reproducible across datasets that are derived from different studies. Our results show that integration of quantitative phosphorylation data with network frameworks can provide mechanistic insights into the differences between the signaling mechanisms that drive BC subtypes. Furthermore, the reproducibility of the identified subnetworks suggests that phosphorylation can provide robust classification of disease response and markers.

Availability and implementation

CoPPNet is available at http://compbio.case.edu/coppnet/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Rtpca: an R package for differential thermal proximity coaggregation analysis
Authors: Kurzawa Nils , Mateus André , Savitski Mikhail M
Published: July 2020

Rtpca is an R package implementing methods for inferring protein–protein interactions (PPIs) based on thermal proteome profiling experiments of a single condition or in a differential setting via an approach called thermal proximity coaggregation. It offers user-friendly tools to explore datasets for their PPI predictive performance and easily integrates with available R packages.

Availability and implementation

Rtpca is available from Bioconductor (https://bioconductor.org/packages/Rtpca).

Supplementary information

Supplementary data are available at Bioinformatics online.
Hive Panel Explorer: an interactive network visualization tool
Authors: Perez Sarah E I , Hahn Aria S , Krzywinski Martin , Hallam Steven J
Published: July 2020

Motivation

Networks are used to relate topological structure to system dynamics and function, particularly in ecology systems biology. Network analysis is often guided or complemented by data-driven visualization. Hive one of many network visualizations, distinguish themselves as providing a general, consistent and coherent rule-based representation to motivate hypothesis development and testing.

Results

Here, we present HyPE, Hive Panel Explorer, a software application that creates a panel of interactive hive plots. HyPE enables network exploration based on user-driven layout rules and parameter combinations for simultaneous of multiple network views. We demonstrate HyPE’s features by exploring a microbial co-occurrence network constructed from forest soil microbiomes.

Availability and implementation

HyPE is available under the GNU license: https://github.com/hallamlab/HivePanelExplorer.

Supplementary information

Supplementary data are available at Bioinformatics online.
Transcriptor: a comprehensive platform for annotation of the enzymatic functions of transcripts
Authors: Ren Ailin , Zhang Dachuan , Tian Yu , Cai Pengli , Zhang Tong , Hu Qian-Nan
Published: July 2020

Motivation

Rapid advances in sequencing technology have resulted huge increases in the accessibility of sequencing data. Moreover, researchers are focusing more on organisms that lack a reference genome. However, few easy-to-use web servers focusing on annotations of enzymatic functions are available. Accordingly, in this study, we describe Transcriptor, a novel platform for annotating transcripts encoding enzymes.

Results

The transcripts were evaluated using more than 300 000 in-house enzymatic reactions through bridges of Enzyme Commission numbers. Transcriptor also enabled ontology term identification and along with associated enzymes, visualization and prediction of domains and annotation of regulatory structure, such as long noncoding RNAs, which could facilitate the discovery of new functions in model or nonmodel species. Transcriptor may have applications in elucidation of the roles of organs transcriptomes and secondary metabolite biosynthesis in organisms lacking a reference genome.

Availability and implementation

Transcriptor is available at http://design.rxnfinder.org/transcriptor/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Persistent minimal sequences of SARS-CoV-2
Authors: Pratas Diogo , Silva Jorge M
Published: July 2020

Motivation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 14 million cases and more than half million deaths. Given the absence of implemented therapies, new analysis, diagnosis and therapeutics are of great importance.

Results

Analysis of SARS-CoV-2 genomes from the current outbreak reveals the presence of short persistent DNA/RNA sequences that are absent from the human genome and transcriptome (PmRAWs). For the PmRAWs with length 12, only four exist at the same location in all SARS-CoV-2. At the gene level, we found one PmRAW of size 13 at the Spike glycoprotein coding sequence. This protein is fundamental for binding in human ACE2 and further use as an entry receptor to invade target cells. Applying protein structural prediction, we localized this PmRAW at the surface of the Spike protein, providing a potential targeted vector for diagnostics and therapeutics. In addition, we show a new pattern of relative absent words (RAWs), characterized by the progressive increase of GC content (Guanine and Cytosine) according to the decrease of RAWs length, contrarily to the virus and host genome distributions. New analysis shows the same property during the Ebola virus outbreak. At a computational level, we improved the alignment-free method to identify pathogen-specific signatures in balance with GC measures and removed previous size limitations.

Availability and implementation

https://github.com/cobilab/eagle.

Supplementary information

Supplementary data are available at Bioinformatics online.
Bringing Botany into Focus: Addressing Plant Blindness in Undergraduates Through an Immersive Botanical Experience
Authors: Colon Jessica , Tiernan Nichole , Oliphant Simone , Shirajee Ateev , Flickinger Jonathan , Liu Hong , Francisco-Ortega Javier , McCartney Melissa
Published: July 2020

Undergraduate science, technology, engineering, and math students (STEM) are usually not attuned to the intricacies of plant life histories or to the dynamic role plants play in ecosystems and human society, a phenomenon termed plant blindness. Botany education has declined in the past decades, whereas career paths that need and benefit from a workforce with botanical knowledge have increased. Consequently, there is a need to reduce plant blindness among undergraduate students, regardless of their career trajectories. We provide evidence that participation in a botanical experience as part of a general biology course can positively shift undergraduates’ perception of botany, the study of plants. Students participating in the botanical experience showed significant positive shifts in their ability to connect botany to their college major and future careers. In addition, we show qualitative data indicating a new respect for plants and a new appreciation for the diversity among plants.
What prevents health policy being ‘evidence-based’? New ways to think about evidence, policy and interventions in health
Authors: Lancaster Kari , Rhodes Tim
Published: July 2020

Background

Evidence-based policy decision-making is a dominant paradigm in health but realizing this ideal has proven challenging.

Sources of data

This paper conceptually maps health policy, policy studies and social science literature critically engaged with evidence and decision-making. No new data were generated or analysed in support of this review.

Areas of agreement

Barriers to evidence-based policy have been documented, with efforts made to increase the uptake of evidence.

Areas of controversy

Evident complexities have been regarded as a problem of translation. However, this assumes that policy-making is a process of authoritative choice, and that ‘evidence’ is inherently valuable policy knowledge, which has been critiqued.

Growing points

Alternative accounts urge consideration of how evidence comes to bear on decisions made within complex systems, and what counts as evidence.

Areas timely for developing research

An ‘evidence-making intervention’ approach offers a framework for conceptualizing how evidence and interventions are made relationally in practices, thus working with the politics and contingencies of implementation and policy-making.
Vascular disease and multiple sclerosis: a post-mortem study exploring their relationships
Authors: Geraldes Ruth , Esiri Margaret M , Perera Rafael , Yee Sydney A , Jenkins Damian , Palace Jacqueline , DeLuca Gabriele C
Published: July 2020

Vascular comorbidities have a deleterious impact on multiple sclerosis clinical outcomes but it is unclear whether this is mediated by an excess of extracranial vascular disease (i.e. atherosclerosis) and/or of cerebral small vessel disease or worse multiple sclerosis pathology. To address these questions, a study using a unique post-mortem cohort wherein whole body autopsy reports and brain tissue were available for interrogation was established. Whole body autopsy reports were used to develop a global score of systemic vascular disease that included aorta and coronary artery atheroma, cardiac hypertensive disease, myocardial infarction and ischaemic stroke. The score was applied to 85 multiple sclerosis cases (46 females, age range 39 to 84 years, median 62.0 years) and 68 control cases. Post-mortem brain material from a subset of the multiple sclerosis (n = 42; age range 39–84 years, median 61.5 years) and control (n = 39) cases was selected for detailed neuropathological study. For each case, formalin-fixed paraffin-embedded tissue from the frontal and occipital white matter, basal ganglia and pons was used to obtain a global cerebral small vessel disease score that captured the presence and/or severity of arteriolosclerosis, periarteriolar space dilatation, haemosiderin leakage, microinfarcts, and microbleeds. The extent of multiple sclerosis-related pathology (focal demyelination and inflammation) was characterized in the multiple sclerosis cases. Regression models were used to investigate the influence of disease status on systemic vascular disease and cerebral small vessel disease scores and, in the multiple sclerosis group, the relationship between multiple sclerosis-related pathology and both vascular scores. We show that: (i) systemic cardiovascular burden, and specifically atherosclerosis, is lower and cerebral small vessel disease is higher in multiple sclerosis cases that die at younger ages compared with control subjects; (ii) the association between systemic vascular disease and cerebral small vessel disease is stronger in patients with multiple sclerosis compared with control subjects; and (iii) periarteriolar changes, including periarteriolar space dilatation, haemosiderin deposition and inflammation, are key features of multiple sclerosis pathology outside the classic demyelinating lesion. Our data argue against a common primary trigger for atherosclerosis and multiple sclerosis but suggest that an excess burden of cerebral small vessel disease in multiple sclerosis may explain the link between vascular comorbidity and accelerated irreversibility disability.
Stable high frequency background EEG activity distinguishes epileptic from healthy brain regions
Authors: Minthe Annika , Janzarik Wibke G , Lachner-Piza Daniel , Reinacher Peter , Schulze-Bonhage Andreas , Dümpelmann Matthias , Jacobs Julia
Published: July 2020

High-frequency oscillations are markers of epileptic tissue. Recently, different patterns of EEG background activity were described from which high-frequency oscillations occur: high-frequency oscillations with continuously oscillating background were found to be primarily physiological, those from quiet background were linked to epileptic tissue. It is unclear, whether these interactions remain stable over several days and during different sleep-wake stages. High-frequency oscillation patterns (oscillatory vs. quiet background) were analysed in 23 patients implanted with depth and subdural grid electrodes. Pattern scoring was performed on every channel in 10 s intervals in three separate day- and night-time EEG segments. An entropy value, measuring variability of patterns per channel, was calculated. A low entropy value indicated a stable occurrence of the same pattern in one channel, whereas a high value indicated pattern instability. Differences in pattern distribution and entropy were analysed for 143 280 10 s intervals with allocated patterns from inside and outside the seizure onset zone, different electrode types and brain regions. We found a strong association between high-frequency oscillations out of quiet background activity, and channels of the seizure onset zone (35.2% inside versus 9.7% outside the seizure onset zone, P < 0.001), no association was found for high-frequency oscillations from continuous oscillatory background (P = 0.563). The type of background activity remained stable over the same brain region over several days and was independent of sleep stage and recording technique. Stability of background activity was significantly higher in channels of the seizure onset zone (entropy mean value 0.56 ± 0.39 versus 0.64 ± 0.41; P < 0.001). This was especially true for the presumed epileptic high-frequency oscillations out of quiet background (0.57 ± 0.39 inside versus 0.72 ± 0.37 outside the seizure onset zone; P < 0.001). In contrast, presumed physiological high-frequency oscillations from continuous oscillatory backgrounds were significantly more stable outside the seizure onset zone (0.72 ± 0.45 versus 0.48 ± 0.53; P < 0.001). The overall low entropy values suggest that interactions between high-frequency oscillations and background activity are a stable phenomenon specific to the function of brain regions. High-frequency oscillations occurring from a quiet background are strongly linked to the seizure onset zone whereas high-frequency oscillations from an oscillatory background are not. Pattern stability suggests distinct underlying mechanisms. Analysing short time segments of high-frequency oscillations and background activity could help distinguishing epileptic from physiologically active brain regions.
Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling
Authors: Hamoya Takahiro , Fujii Gen , Iizumi Yosuke , Narita Takumi , Komiya Masami , Matsuzawa Yui , Miki Kohei , Kondo Tadashi , Kishimoto Shinji , Watanabe Kenji , Wakabayashi Keiji , Sakai Toshiyuki , Toshima Jiro , Mutoh Michihiro
Published: July 2020

Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.
Cell Surface Protein mRNAs Show Differential Transcription in Pyramidal and Fast-Spiking Cells as Revealed by Single-Cell Sequencing
Authors: Ravasz Lilla , Kékesi Katalin Adrienna , Mittli Dániel , Todorov Mihail Ivilinov , Borhegyi Zsolt , Ercsey-Ravasz Mária , Tyukodi Botond , Wang Jinhui , Bártfai Tamás , Eberwine James , Juhász Gábor
Published: July 2020

The prefrontal cortex (PFC) plays a key role in higher order cognitive functions and psychiatric disorders such as autism, schizophrenia, and depression. In the PFC, the two major classes of neurons are the glutamatergic pyramidal (Pyr) cells and the GABAergic interneurons such as fast-spiking (FS) cells. Despite extensive electrophysiological, morphological, and pharmacological studies of the PFC, the therapeutically utilized drug targets are restricted to dopaminergic, glutamatergic, and GABAergic receptors. To expand the pharmacological possibilities as well as to better understand the cellular and network effects of clinically used drugs, it is important to identify cell-type-selective, druggable cell surface proteins and to link developed drug candidates to Pyr or FS cell targets. To identify the mRNAs of such cell-specific/enriched proteins, we performed ultra-deep single-cell mRNA sequencing (19 685 transcripts in total) on electrophysiologically characterized intact PFC neurons harvested from acute brain slices of mice. Several selectively expressed transcripts were identified with some of the genes that have already been associated with cellular mechanisms of psychiatric diseases, which we can now assign to Pyr (e.g., Kcnn2, Gria3) or FS (e.g., Kcnk2, Kcnmb1) cells. The earlier classification of PFC neurons was also confirmed at mRNA level, and additional markers have been provided.
Systematic Severe Acute Respiratory Syndrome Coronavirus 2 Screening at Hospital Admission in Children: A French Prospective Multicenter Study
Authors: Poline Julie , Gaschignard Jean , Leblanc Claire , Madhi Fouad , Foucaud Elsa , Nattes Elodie , Faye Albert , Bonacorsi Stéphane , Mariani Patricia , Varon Emmanuelle , Smati-Lafarge Mounira , Caseris Marion , Basmaci Romain , Lachaume Noémie , Ouldali Naïm
Published: July 2020

To assess the relevance of systematic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening of all children admitted to hospital, we conducted a prospective multicenter study including 438 consecutive hospitalized children. A symptom-based SARS-CoV-2 testing strategy failed to identify 45% (95% confidence interval, 24%–68%) of hospitalized children infected by SARS-CoV-2. To limit intrahospital transmission, a systematic screening of children admitted to hospital should be considered.
Safety, Tolerability, and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine (PCV20) in Adults 60 to 64 Years of Age
Authors: Hurley Donald , Griffin Carl , Young Mariano , Scott Daniel A , Pride Michael W , Scully Ingrid L , Ginis John , Severs Joseph , Jansen Kathrin U , Gruber William C , Watson Wendy
Published: July 2020

Background

Pneumococcal conjugate vaccines (PCVs) have significantly decreased pneumococcal disease worldwide; however, expanding serotype coverage may further reduce disease burden. A 20-valent PCV (PCV20) containing capsular polysaccharide conjugates of serotypes present in the 13-valent PCV (PCV13) and 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) is currently in development. This phase 2 study evaluated safety, tolerability, and immunogenicity of PCV20 in adults without prior pneumococcal vaccination.

Methods

In this randomized, active-controlled, double-blinded trial, 444 adults 60 through 64 years of age were randomized to receive either a single dose of PCV20 followed 1 month later by saline placebo or a single dose of PCV13 followed 1 month later by 23-valent polysaccharide vaccine. Local injection site reactions, select systemic symptoms, and adverse events (AEs) were recorded. Immunogenicity was assessed by measuring serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month after each vaccination.

Results

Local reaction and systemic event rates were similar after vaccination with PCV20 or PCV13; no serious vaccine-related AEs were reported. In the PCV20 group, functional immune responses as measured by OPA were robust for all 20 serotypes included in the vaccine, with geometric mean fold rises from baseline ranging from 6.0 to 113.4.

Conclusions

PCV20 was well tolerated in adults 60 to 64 years of age, with a safety profile consistent with historical experience of PCVs in this age group. Substantial OPA responses were elicited against all serotypes. Results demonstrate the potential for PCV20 to expand pneumococcal disease protection.

Clinical Trials Registration

NCT03313037.
The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression
Authors: Moron-Lopez Sara , Urrea Victor , Dalmau Judith , Lopez Miguel , Puertas Maria C , Ouchi Dan , Gómez Antonio , Passaes Caroline , Mothe Beatriz , Brander Christian , Saez-Cirion Asier , Clotet Bonaventura , Esteller Manel , Berdasco Maria , Martinez-Picado Javier
Published: July 2020

Background

Human genetic variation—mostly in the human leukocyte antigen (HLA) and C–C chemokine receptor type 5 (CCR5) regions—explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection.

Methods

In total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART.

Results

We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg.

Conclusions

Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART.
Individual-level Association of Influenza Infection With Subsequent Pneumonia: A Case-control and Prospective Cohort Study
Authors: Kubale John , Kuan Guillermina , Gresh Lionel , Ojeda Sergio , Schiller Amy , Sanchez Nery , Lopez Roger , Azziz-Baumgartner Eduardo , Wraith Steph , Harris Eva , Balmaseda Angel , Zelner Jon , Gordon Aubree
Published: July 2020

Background

Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined.

Methods

We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0–14 years from 2011 through 2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian nonlinear survival model to estimate pneumonia hazard following influenza.

Results

Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR], 2.7 [95% confidence interval {CI}, 1.9–3.9]). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR, 3.7 [95% CI, 2.0–6.9]), followed by influenza B and A(H3N2). Participants’ odds of pneumonia following influenza were not constant, showing distinct peaks 0–6 days (mOR, 8.3 [95% CI, 4.8–14.5] days) and 14–20 (mOR, 2.5 [95% CI, 1.1–5.5] days) after influenza infection.

Conclusions

Influenza is a significant driver of both primary and secondary pneumonia among children. The presence of distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.
SARS-CoV-2 in Rural Latin America. A Population-based Study in Coastal Ecuador
Authors: Del Brutto Oscar H , Costa Aldo F , Mera Robertino M , Recalde Bettsy Y , Bustos Javier A , García Héctor H
Published: July 2020

Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were detected in 303/673 rural Ecuadorian adults (45%), 77% of whom had compatible clinical manifestations. Seropositivity was associated with the use of open latrines. Our findings support the fears of mass spread of SARS-CoV-2 in rural Latin America and cannot exclude a contributing role for fecal-oral transmission.
Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling
Authors: Vigil-Garcia Marta , Demkes Charlotte J , Eding Joep E C , Versteeg Danielle , de Ruiter Hesther , Perini Ilaria , Kooijman Lieneke , Gladka Monika M , Asselbergs Folkert W , Vink Aryan , Harakalova Magdalena , Bossu Alexander , van Veen Toon A B , Boogerd Cornelis J , van Rooij Eva
Published: July 2020

Aims

Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling.

Methods and results

Utilizing CM-specific reporter mice exposed to pressure overload by transverse aortic banding and CM isolation by flow cytometry, we obtained gene expression profiles of hypertrophic CMs in the more immediate phase after stress, and CMs showing pathological hypertrophy. We identified subsets of genes differentially regulated and specific for either stage. Among the genes specifically up-regulated in the CMs during the maladaptive phase we found known stress markers, such as Nppb and Myh7, but additionally identified a set of genes with unknown roles in pathological hypertrophy, including the platelet isoform of phosphofructokinase (PFKP). Norepinephrine-angiotensin II treatment of cultured human CMs induced the secretion of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and recapitulated the up-regulation of these genes, indicating conservation of the up-regulation in failing CMs. Moreover, several genes induced during pathological hypertrophy were also found to be increased in human HF, with their expression positively correlating to the known stress markers NPPB and MYH7. Mechanistically, suppression of Pfkp in primary CMs attenuated stress-induced gene expression and hypertrophy, indicating that Pfkp is an important novel player in pathological remodelling of CMs.

Conclusion

Using CM-specific transcriptomic analysis, we identified novel genes induced during pathological hypertrophy that are relevant for human HF, and we show that PFKP is a conserved failure-induced gene that can modulate the CM stress response.
A Global, Prospective, Observational Study Measuring Disease Burden and Suffering in Patients With Ulcerative Colitis, Using the Pictorial Representation of Illness and Self-measure Tool
Authors: Ghosh Subrata , Sensky Tom , Casellas Francesc , Rioux Louis-Charles , Ahmad Tariq , Márquez Juan R , Vanasek Tomas , Gubonina Irina , Sezgin Orhan , Ardizzone Sandro , Kligys Kristina , Petersson Joel , Suzuki Yasuo , Peyrin-Biroulet Laurent
Published: July 2020

Background

The understanding the Impact of ulcerative COlitis aNd Its assoCiated disease burden on patients study [ICONIC] was a 2-year, global, prospective, observational study evaluating the cumulative burden of ulcerative colitis [UC] using the Pictorial Representation of Illness and Self-Measure [PRISM] tool that is validated to measure suffering, but has not previously been used in UC.

Methods

ICONIC enrolled unselected outpatient clinic attenders with recent-onset UC. Patient- and physician-reported outcomes including PRISM, the Short Inflammatory Bowel Disease Questionnaire [SIBDQ], the Patient Health Questionnaire [PHQ-9], and the Simple Clinical Colitis Activity Indexes [patient: P-SCCAI; physician: SCCAI] were collected at baseline and follow-up visits every 6 months. Correlations between these measures were assessed using Spearman’s rank correlation coefficient.

Results

Overall, 1804 evaluable patients had ≥1 follow-up visit. Over 24 months, mean [SD] disease severity measured by P-SCCAI/SCCAI reduced significantly from 4.2 [3.6]/3.0 [3.0] to 2.4 [2.7]/1.3 [2.1] [p <0.0001]. Patient-/physician-assessed suffering, quantified by PRISM, reduced significantly over 24 months [p <0.0001]. P-SCCAI/SCCAI and patient-/physician-assessed PRISM showed strong pairwise correlations [rho ≥0.60, p <0.0001], although physicians consistently underestimated these disease severity and suffering measures compared with patients. Patient-assessed PRISM moderately correlated with other outcome measures, including SIBDQ, PHQ-9, P-SCCAI, and SCCAI (rho = ≤-0.38 [negative correlations] or ≥0.50 [positive correlations], p <0.0001).

Conclusions

Over 2 years, disease burden and suffering, quantified by PRISM, improved in patients with relatively early UC. Physicians underestimated burden and suffering compared with patients. PRISM correlated with other measures of illness perception in patients with UC, supporting its use as an endpoint reflecting patient suffering.
Dispersal of Lycorma delicatula (Hemiptera: Fulgoridae) Nymphs Through Contiguous, Deciduous Forest
Authors: Keller Joseph A , Johnson Anne E , Uyi Osariyekemwen , Wurzbacher Sarah , Long David , Hoover Kelli
Published: July 2020

Spotted lanternfly (Lycorma delicatula) is a recently introduced pest in the United States, where it threatens the wine, timber, and ornamentals industries. Knowledge of the dispersal ability of L. delicatula is key to developing effective management strategies for this invasive pest. We conducted a mark, release, re-sight study, marking nymphs with fluorescent powders and observing dispersal distances from a central release point at three time points over 7 d following release. To examine how dispersal patterns changed over the course of nymphal development, we repeated this process for each of L. delicatula’s four instars. All releases were conducted in contiguous, deciduous forest, which is a widespread habitat type within L. delicatula’s invaded range and a habitat where this pest may have negative ecological and economic impacts. We found that nymphs displayed clear directionality in their movement following release, apparently preferring to move uphill on the modest 6° grade at our release site. Most nymphs remained near the release location, while some moved tens of meters. The maximum displacement we observed was 65 m from the release point, 10 d after release. Nymphs were re-sighted singly and in small groups on a variety of trees, shrubs, and understory vegetation. All four instars had similar dispersal distances over time, though third instar nymphs moved farthest on average, with estimated median displacement of 16.9 m 7 d after release. Further studies are needed to provide additional information on what factors influence spotted lanternfly dispersal.
Carbon Neutral: The Failure of Dung Beetles (Coleoptera: Scarabaeidae) to Affect Dung-Generated Greenhouse Gases in the Pasture
Authors: Fowler Fallon , Denning Steve , Hu Shuijin , Watson Wes
Published: July 2020

Research suggests dung beetles can churn, aerate, and desiccate dung in ways that influence the dung and soil microbes producing greenhouse gases (GHGs). We examined the impacts of the tunneling beetle, Onthophagus taurus (Schreber), and the dwelling beetle, Labarrus pseudolividus (Balthasar), on the carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) emitted from pasture-laid bovine dung as well as their sum-total (CO2 + CH4 + N2O) effect on global warming, or their carbon dioxide equivalent (CO2e). Despite dung beetles potential effects on CH4 and N2O, the existing literature shows no ultimate CO2e reductions. We hypothesized that more dung beetles would degrade pats faster and reduce CO2e, and so we increased the average dung beetle biomass per dung volume 6.22× above previously published records, and visually documented any dung damage. However, the time effects were 2–5× greater for any GHG and CO2e (E = 0.27–0.77) than dung beetle effects alone (E = 0.09–0.24). This suggests that dung beetle communities cannot adequately reduce GHGs unless they can accelerate dung decomposition faster than time alone.
Risk of fracture in patients with non-valvular atrial fibrillation initiating direct oral anticoagulants vs. vitamin K antagonists
Authors: He Na , Dell'Aniello Sophie , Zhai Suodi , Suissa Samy , Renoux Christel
Published: July 2020

Aims

To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use.

Methods and results

Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46–0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31–0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79–1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls.

Conclusion

Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.
Water management and phenology influence the root-associated rice field microbiota
Authors: Chialva Matteo , Ghignone Stefano , Cozzi Paolo , Lazzari Barbara , Bonfante Paola , Abbruscato Pamela , Lumini Erica
Published: July 2020

Microbial communities associated with plants are greatly influenced by water availability in soil. In flooded crops, such as rice, the impact of water management on microbial dynamics is not fully understood. Here, we present a comprehensive study of the rice microbiota investigated in an experimental field located in one of the most productive areas of northern Italy. The microbiota associated with paddy soil and root was investigated using 454 pyrosequencing of 16S, ITS and 18S rRNA gene amplicons under two different water managements, upland (non-flooded, aerobic) and lowland (traditional flooding, anaerobic), at three plant development stages. Results highlighted a major role of the soil water status in shaping microbial communities, while phenological stage had low impacts. Compositional shifts in prokaryotic and fungal communities upon water management consisted in significant abundance changes of Firmicutes, Methanobacteria, Chloroflexi, Sordariomycetes, Dothideomycetes and Glomeromycotina. A vicariance in plant beneficial microbes and between saprotrophs and pathotrophs was observed between lowland and upland. Moreover, through network analysis, we demonstrated different co-abundance dynamics between lowland and upland conditions with a major impact on microbial hubs (strongly interconnected microbes) that fully shifted to aerobic microbes in the absence of flooding.
Improved multichannel singular spectrum analysis for post-processing GRACE monthly gravity field models
Authors: Wang Fengwei , Shen Yunzhong , Chen Tianyi , Chen Qiujie , Li Weiwei
Published: July 2020

Multichannel singular spectrum analysis (MSSA) is a powerful tool to extract spatiotemporal signals and filter errors from the noisy time-series of monthly gravity field models from the satellite data of gravity recovery and climate experiment (GRACE). Since the GRACE monthly gravity models are missed about 17 months, we develop an improved MSSA approach, which can directly process the incomplete time-series without either data interpolation or iteration. The time-series of 14-yr (2002.04–2016.08) monthly gravity field models of CSR-RL06 up to degree and order 60 are analysed with improved MSSA compared to the MSSA with linear data interpolation and iteration MSSA. By using our improved MSSA approach, the first 11 principal components derived can capture 91.18 per cent of the total variance, higher than 85.80 and 86.44 per cent of the total variance, derived by linear interpolation MSSA and iteration MSSA, respectively. The ratios of the latitude weighted RMS over the land and ocean signals are used to evaluate the efficiency of eliminating noise by the MSSA approach. For improved MSSA, the mean RMS ratio of land and ocean signals of all available months is higher than linear interpolation and iteration MSSA, which indicates that improved MSSA can suppress noise more efficiently and extract more geophysical signals from real GRACE data. Furthermore, the 50 repeated experiments show that all the root mean squared errors and mean absolute errors derived by our improved MSSA are smaller than other MSSA approaches. Moreover, the improved MSSA performs still better than other MSSA based approaches for the cases of large data gaps.
Erbb4 regulates the oocyte microenvironment during folliculogenesis
Authors: Veikkolainen Ville , Ali Nsrein , Doroszko Milena , Kiviniemi Antti , Miinalainen Ilkka , Ohlsson Claes , Poutanen Matti , Rahman Nafis , Elenius Klaus , Vainio Seppo J , Naillat Florence
Published: July 2020

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, endocrine and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-Müllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.