bluuebunny/crossref_metadata_2025 huggingface dataset:
A Liquid drop Falling in Another Fluid: A Two-Phase Flow Phenomenon
Authors: Xia Wendi
Published: September 2021

Liquid drops exist everywhere in daily life. However, such a common phenomenon involves complex mechanisms, and therefore has never been investigated thoroughly—the achievements of the studies are limited and unsatisfactory. In this article, the phenomenon of a liquid drop falling in another immiscible fluid (mostly its settling speed) was investigated. A series of experiments, in which liquid drops emerging from a syringe falls inside a measuring cylinder filled another fluid, was performed. Fluids used in the experiment include ethanol solutions and rice bran oil; for rice bran oil, its temperature-dependent viscosity was approximated by a function, which was proved effective on other similar oils. The dependence of the settling speed of the liquid drop on the density difference between the liquid drop and the surrounding fluid, as well as on the temperature of the surrounding fluid, was measured. Finite-Element Modeling (FEM) simulations were then carried out to model these situations, and lead to results that agreed with the experiments. It also visualized the flow field and revealed more details of the two-phase flow that were not detectable by our devices. Furthermore, inspired by some previous formulae, quantitative equations were derived semi-analytically by modifying an approximate drag formula originally developed for a rigid object at moderate Reynolds numbers. The form of the modification was never introduced in any other previous works. The equations were validated by simulations under ideal conditions.
Cryogenic pre-amplifier for liquid xenon applications
Authors: Arneodo F. , Bruno G. , Conicella V. , Di Giovanni A. , Franchi G. , Manenti L.
Published: September 2021

Several liquid xenon experiments for rare event searches are using the photomultiplier Hamamatsu R11410 for scintillation light detection.

In this work, a low-noise charge pre-amplifier designed for liquid xenon applications is tested at cryogenic temperatures, in combination with this specific photomultiplier. Results will be presented and discussed.
Metamorphic Evolution of Calc-silicate Rocks at Akarui Point, Lützow-Holm Complex, East Antarctica
Authors: Amnatmetta Bowornlak , Booth John , Nantasin Prayath , Kim Yoonsup
Published: September 2021

We report on the petrology and metamorphic history of boudined bodies of zoned calc-silicate rock, up to 1 m in width, which are enclosed in gneisses, transitional between upper amphibolite to granulite facies, at Akarui Point, Lützow-Holm Complex, East Antarctica. Zircons extracted from a closely related body of Mn-exhalative derived calc-silicates indicate that the metamorphism occurred in two separate events, at 546.6 ± 0.6 and 524.3 ± 0.6 Ma, during the Pan African Orogeny. Based on the meionite content of scapolite from different mineral zones in the calc-silicates, we derive a metamorphic history that involved a peak temperature of a minimum 810 – 820 °C, followed by a fall to 760-800 °C and then to 690-765 °C during uplift and decompression to 5.5 – 7 kbar. GAP geothermo-barometry indicates that the enclosing gneiss partially re-equilibrated during retrogression at 500-580 °C.
Literature Review: How Does Water Play a Role in Forming Land Value?
Authors: Adelina C , Gamal A , Marthanty D R
Published: September 2021

This research synthesizes the causality of water: the supply of clean water and water-related disasters in forming the land value. Water has a significant relation to real estate. For example, the developing design at the built area will take much investment value to supply its clean water individually. Secondly, the damaged property caused by water-related disasters will make much value to invest in repairs. In other words, the considerable investment will take a role in it. This research uses a qualitative method by synthesizing literature reviews of water-related disasters, clean water supply, and property. This research found that the previous researchers correlated water-related disasters, clean water supply, or quality to property, respectively. However, no research has examined all the water’s roles to property in our knowledge. Therefore, there is a suggestion for further research to prove this research using the quantitative method to relate the water’s roles and land value.
Biocompatibility of 2D silicon nitride: interaction at the nano-bio interface
Authors: Shekaari Ashkan , Jafari Mahmoud
Published: September 2021

Determining potential abilities of nanostructures to induce toxicity to biological molecules is still a convoluted challenge in the realm of nanomedicine. Based on the unprecedented achievements of two-dimensional nanomaterials in nearly all areas of applied sciences particularly medicine, we carried out all-atom molecular dynamics simulations to assess the biologically important, yet unmapped issue of biocompatibility of 2D, hexagonalβ-Si3N4nanosheet via investigating its possible cross interactions with both human serum albumin (HSA) and p53 tumor suppressor. Examining the conventional MD indicators in presence and absence of the monolayer revealed that hexagonal Si3N4nanosheet weakly binds to these two proteins without inducing any important, dramatic change to their secondary structures, revealing accordingly the biological compatibility of the monolayer in case it is released as therapeutics or carriersin vivo. This finding was also broadly supported by the related time-dependent behaviors of the protein-monolayer as well as the protein-water interaction energies.
Investigation on the serrated flow behavior of bulk metallic glasses based on machine learning
Authors: Zhao M S Z , Long Z L , Peng L
Published: September 2021

This study proposed a long short-term memory (LSTM) model for predicting the serrated flow behaviors of bulk metallic glasses (BMGs) under nanoindentation. A series of load-controlled nanoindentation tests were conducted on a Pd40Cu30Ni10P20 BMG. The LSTM model was introduced to establish a neural network for predicting the serrated flow at different loading rates, and was verified by the comparisons of experimental data with predictive results. Further investigation based on the predictive serrated flows under different loading rates showed that the serrations exhibit a significant self-organized critical (SOC) phenomenon at different loading rates. The SOC phenomena of the serrations under a lower loading rate were more obvious than that under a higher loading rate.
Indicators of climate risk in the UK at different levels of warming
Authors: Arnell Nigel W , Freeman Anna , Kay Alison L , Rudd Alison C , Lowe Jason A
Published: September 2021

Assessments of the impacts of climate change are typically made using climate scenarios based on assumptions about future emissions of greenhouse gases, but policymakers and climate risk communicators are increasingly asking for information on impacts at different levels of warming. This paper provides this information for a set of indicators of climate risks in the UK for levels of warming up to 4 °C above pre-industrial levels. The results show substantial increases in climate risks at 2 °C, which is often inferred in the media to be a ‘safe’ level of climate change. In a 2 °C world, the chance of a heatwave is doubled, and the frequency of heat stress affecting people, crops and animals can be increased by a factor of five. Cooling degree days more than double, wildfire danger can increase by 40%–70%, the frequency of agricultural and water resources droughts doubles in England, and flood frequency in Wales increases by 50%. At 4 °C the increases in risk are considerably greater: heatwaves occur in virtually every year. The frequency of cold weather extremes reduces, but is not eliminated, with increasing warming. The rate of change in an indicator with warming varies across the UK. For temperature-based indicators this reflects variability in current climate, but for rainfall-based indicators reflects variations in the change in climate. Most indicators show a generally linear increase in risk with level of warming (although the change in risk from now is around 2.4 times higher in a 4 °C world than a 2 °C world because of warming experienced so far). However, some indicators—particularly relating to heat extremes—show a highly non-linear increase with level of warming. The range in change in indicator at a given level of warming is primarily caused by uncertainty in the estimated regional response of to increasing forcing.
What is critical about criticality: in praise of the correlation function
Authors: Jensen Henrik Jeldtoft
Published: September 2021

We present a brief review of power laws and correlation functions as measures of criticality and the relation between them. By comparing phenomenology from rain, brain and the forest fire model we discuss the relevant features of self-organisation to the vicinity about a critical state. We conclude that organisation to a region of extended correlations and approximate power laws may be behaviour of interest shared between the three considered systems.
Dopant network processing units: towards efficient neural network emulators with high-capacity nanoelectronic nodes
Authors: Ruiz-Euler Hans-Christian , Alegre-Ibarra Unai , van de Ven Bram , Broersma Hajo , Bobbert Peter A , van der Wiel Wilfred G
Published: September 2021

The rapidly growing computational demands of deep neural networks require novel hardware designs. Recently, tuneable nanoelectronic devices were developed based on hopping electrons through a network of dopant atoms in silicon. These ‘dopant network processing units’ (DNPUs) are highly energy-efficient and have potentially very high throughput. By adapting the control voltages applied to its electrodes, a single DNPU can solve a variety of linearly non-separable classification problems. However, using a single device has limitations due to the implicit single-node architecture. This paper presents a promising novel approach to neural information processing by introducing DNPUs as high-capacity neurons and moving from a single to a multi-neuron framework. By implementing and testing a small multi-DNPU classifier in hardware, we show that feed-forward DNPU networks improve the performance of a single DNPU from 77% to 94% test accuracy on a binary classification task with concentric classes on a plane. Furthermore, motivated by the integration of DNPUs with memristor crossbar arrays, we study the potential of using DNPUs in combination with linear layers. We show by simulation that an MNIST classifier with only 10 DNPU nodes achieves over 96% test accuracy. Our results pave the road towards hardware neural network emulators that offer atomic-scale information processing with low latency and energy consumption.
A system design perspective on neuromorphic computer processors
Authors: Rose Garrett S , Shawkat Mst Shamim Ara , Foshie Adam Z , Murray John J , Adnan Md Musabbir
Published: September 2021

Neuromorphic computing has become an attractive candidate for emerging computing platforms. It requires an architectural perspective, meaning the topology or hyperparameters of a neural network is key to realizing sound accuracy and performance in neural networks. However, these network architectures must be executed on some form of computer processor. For machine learning, this is often done with conventional computer processing units, graphics processor units, or some combination thereof. A neuromorphic computer processor or neuroprocessor, in the context of this paper, is a hardware system that has been designed and optimized for executing neural networks of one flavor or another. Here, we review the history of neuromorphic computing and consider various spiking neuroprocessor designs that have emerged over the years. The aim of this paper is to identify emerging trends and techniques in the design of such brain-inspired neuroprocessor computer systems.
Feasibility of remote Memory Clinics using the plan, do, study, act (PDSA) cycle
Authors: Collins Jemima T , Mohamed Biju , Bayer Antony
Published: September 2021

Introduction

A timely diagnosis of dementia is crucial for initiating and maintaining support for people living with dementia. The coronavirus disease (COVID) pandemic temporarily halted Memory Clinics, where this is organised, and rate of dementia diagnosis has fallen. Despite increasing use of alternatives to face-to-face (F2F) consultations in other departments, it is unclear whether this is feasible within the traditional Memory Clinic model.

Aims

The main aim of this service improvement project performed during the pandemic was to explore feasibility of telephone (TC) and videoconference (VC) Memory Clinic consultations.

Methods

Consecutive patients on the Memory Clinic waiting list were telephoned and offered an initial appointment by VC or TC. Data extracted included: age, internet-enabled device ownership, reason for and choice of Memory Clinic assessment. We noted Montreal Cognitive Assessment-Blind (TC) and Addenbrooke’s Cognitive Examination-III (VC via Attend Anywhere) scores, and feasibility of consultation.

Results

Out of 100 patients, 12 had a home assessment, moved away, been hospitalised, or died. 45, 21 and 6 preferred F2F, VC and TC assessments respectively. 16 were not contactable and offered a F2F appointment. The main reason for preferring F2F was non-ownership, or inability to use an internet-enabled device (80%). VC and TC preference reasons were unwillingness to come to hospital (59%), and convenience (41%). Attendance rate was 100% for VC and TC, but 77% for F2F. Feasibility (successful consultations) was seen in 90% (VC) and 67% (TC) patients.

Conclusion

For able and willing patients, remote Memory Consultations can be both feasible and beneficial. This has implications for future planning in dementia services.
Estimation of Dermal Exposure to Oil Spill Response and Clean-up Workers after the Deepwater Horizon Disaster
Authors: Stewart Patricia A , Gorman Ng Melanie , Cherrie John W , Jones Anna , Kwok Richard K , Blair Aaron , Engel Lawrence S , Sandler Dale P , Stenzel Mark R
Published: September 2021

The GuLF STUDY is investigating health outcomes associated with oil spill-related chemical exposures among workers involved in the spill response and clean-up following the Deepwater Horizon disaster. Due to the lack of dermal exposure measurements, we estimated dermal exposures using a deterministic model, which we customized from a previously published model. Workers provided information on the frequency of contact with oil, tar, chemical dispersants applied to the oil spill and sea water, as well as the use of protective equipment, by job/activity/task. Professional judgment by industrial hygienists served as a source of information for other model variables. The model estimated dermal exposures to total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, n-hexane (BTEX-H), polycyclic aromatic hydrocarbons (PAHs), and dispersants in GuLF DREAM units (GDUs). Arithmetic means (AMs) of THC exposure estimates across study participants ranged from <0.02 to 5.50 GDUs for oil and <0.02 to 142.14 GDUs for tar. Statistical differences in the estimates were observed among the AMs of the estimates for some broad groups of worker activities over time and for some time periods across the broad groups of activities. N-Hexane had ranges similar to THC for oil exposures (e.g. AMs up to 2.22 GDUs) but not for tar (up to 5.56 GDUs). Benzene, ethylbenzene, toluene, and xylene, in contrast, were characterized by higher exposure levels than THC for oil (AMs up to 12.77, 12.17, 17.45, and 36.77 GDUs, respectively) but lower levels than THC to tar (AMs up to 3.69, 11.65, 42.37, and 88.18 GDUs, respectively). For PAHs, the AMs were as high as 219.31 and 587.98 for oil and tar, respectively. Correlations of these seven substances to each other were high (>0.9) for most of the substances in oil but were lower for some of the substances in tar. These data were linked to the study participants to allow investigation of adverse health effects that may be related to dermal exposures.
The Impact of COVID-19 on Transit Workers: Perceptions of Employer Responses and Associations with Health Factors
Authors: Rice Sean P M , Greenspan Leah S , Bauer Talya N , Rimby Jarred , Bodner Todd E , Olson Ryan
Published: September 2021

COVID-19 has had a substantial impact on transit workers’ lives, especially among public-facing vehicle operators. The current project examined relationships between workers’ knowledge and perceptions of their employer’s COVID-19 safety responses, job attitudes, and health. We surveyed transit workers (N = 174) between July and August 2020 and followed up 3 months later. Fifty-seven workers responded to the follow-up survey. Surveys addressed workers’ knowledge and perceptions of their employer implementing Centers for Disease Control and Prevention (CDC)-recommended COVID-19 safety responses, COVID-19 risk perceptions, job attitudes, and health factors. Employees reported knowledge of their employer implementing ~8 of 12 CDC-recommended responses. The most reported response was informational poster placements; the least reported was designating a point-person for COVID-19 concerns. Significant associations were found between knowledge of employer safety responses and lower COVID-19 risk perceptions, better job attitudes, and greater mental and global health. Operators (i.e. public-facing workers) reported worse perceptions of employer responses, and higher COVID-19 risk perceptions, work stress, and turnover intentions, compared with non-operators. A time-lagged panel model found that COVID-19 risk perceptions significantly mediated the relationship between public-facing work status and follow-up depression, anxiety, stress, and global health. Results reveal opportunities for transit authorities to broaden and better communicate their responses to emergent occupational safety and health crises.
Translanguaging Health
Authors: Brooks Emma
Published: September 2021

This article considers the complex communicative practices of contemporary consultations in a superdiverse London hospital, as staff and patients employ the breadth of their linguistic and semiotic resources to navigate health information, in an attempt to ensure mutual comprehension. Drawing on observations of antenatal appointments, I investigate how creative and flexible interaction appears to enhance patient experience, and present data which seem to extend notions of settings that can be understood to offer a translanguaging space. Yet tensions lie in the epistemological emancipation and parity that the conditions of superdiverse consultations can be seen to imply, as such circumstances may also hold the potential for situational, or clinical, consequences. Similarly, although creative repertoires appear to transcend and transform bounded notions of language, I note that their exploitation nevertheless remains contingent on the flexibility of the personal and institutional affordances available—the instigation of which ultimately rest with those in positions of authority.
CRIS: complete reconstruction of immunoglobulin V-D-J sequences from RNA-seq data
Authors: Islam Rashedul , Bilenky Misha , Weng Andrew P , Connors Joseph M , Hirst Martin
Published: September 2021

Motivation

B cells display remarkable diversity in producing B-cell receptors through recombination of immunoglobulin (Ig) V-D-J genes. Somatic hypermutation (SHM) of immunoglobulin heavy chain variable (IGHV) genes are used as a prognostic marker in B-cell malignancies. Clinically, IGHV mutation status is determined by targeted Sanger sequencing which is a resource-intensive and low-throughput procedure. Here, we describe a bioinformatic pipeline, CRIS (Complete Reconstruction of Immunoglobulin IGHV-D-J Sequences) that uses RNA sequencing (RNA-seq) datasets to reconstruct IGHV-D-J sequences and determine IGHV SHM status.

Results

CRIS extracts RNA-seq reads aligned to Ig gene loci, performs assembly of Ig transcripts and aligns the resulting contigs to reference Ig sequences to enumerate and classify SHMs in the IGHV gene sequence. CRIS improves on existing tools that infer the B-cell receptor repertoire from RNA-seq data using a portion IGHV gene segment by de novo assembly. We show that the SHM status identified by CRIS using the entire IGHV gene segment is highly concordant with clinical classification in three independent chronic lymphocytic leukemia patient cohorts.

Availability and implementation

The CRIS pipeline is available under the MIT License from https://github.com/Rashedul/CRIS.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
RoDiCE: robust differential protein co-expression analysis for cancer complexome
Authors: Matsui Yusuke , Abe Yuichi , Uno Kohei , Miyano Satoru
Published: September 2021

Motivation

The full spectrum of abnormalities in cancer-associated protein complexes remains largely unknown. Comparing the co-expression structure of each protein complex between tumor and healthy cells may provide insights regarding cancer-specific protein dysfunction. However, the technical limitations of mass spectrometry-based proteomics, including contamination with biological protein variants, causes noise that leads to non-negligible over- (or under-) estimating co-expression.

Results

We propose a robust algorithm for identifying protein complex aberrations in cancer based on differential protein co-expression testing. Our method based on a copula is sufficient for improving identification accuracy with noisy data compared to conventional linear correlation-based approaches. As an application, we use large-scale proteomic data from renal cancer to show that important protein complexes, regulatory signaling pathways and drug targets can be identified. The proposed approach surpasses traditional linear correlations to provide insights into higher-order differential co-expression structures.

Availability and implementation

https://github.com/ymatts/RoDiCE.

Supplementary information

Supplementary data are available at Bioinformatics online.
PsiNorm: a scalable normalization for single-cell RNA-seq data
Authors: Borella Matteo , Martello Graziano , Risso Davide , Romualdi Chiara
Published: September 2021

Motivation

Single-cell RNA sequencing (scRNA-seq) enables transcriptome-wide gene expression measurements at single-cell resolution providing a comprehensive view of the compositions and dynamics of tissue and organism development. The evolution of scRNA-seq protocols has led to a dramatic increase of cells throughput, exacerbating many of the computational and statistical issues that previously arose for bulk sequencing. In particular, with scRNA-seq data all the analyses steps, including normalization, have become computationally intensive, both in terms of memory usage and computational time. In this perspective, new accurate methods able to scale efficiently are desirable.

Results

Here, we propose PsiNorm, a between-sample normalization method based on the power-law Pareto distribution parameter estimate. Here, we show that the Pareto distribution well resembles scRNA-seq data, especially those coming from platforms that use unique molecular identifiers. Motivated by this result, we implement PsiNorm, a simple and highly scalable normalization method. We benchmark PsiNorm against seven other methods in terms of cluster identification, concordance and computational resources required. We demonstrate that PsiNorm is among the top performing methods showing a good trade-off between accuracy and scalability. Moreover, PsiNorm does not need a reference, a characteristic that makes it useful in supervised classification settings, in which new out-of-sample data need to be normalized.

Availability and implementation

PsiNorm is implemented in the scone Bioconductor package and available at https://bioconductor.org/packages/scone/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Structure-aware protein–protein interaction site prediction using deep graph convolutional network
Authors: Yuan Qianmu , Chen Jianwen , Zhao Huiying , Zhou Yaoqi , Yang Yuedong
Published: September 2021

Motivation

Protein–protein interactions (PPI) play crucial roles in many biological processes, and identifying PPI sites is an important step for mechanistic understanding of diseases and design of novel drugs. Since experimental approaches for PPI site identification are expensive and time-consuming, many computational methods have been developed as screening tools. However, these methods are mostly based on neighbored features in sequence, and thus limited to capture spatial information.

Results

We propose a deep graph-based framework deep Graph convolutional network for Protein–Protein-Interacting Site prediction (GraphPPIS) for PPI site prediction, where the PPI site prediction problem was converted into a graph node classification task and solved by deep learning using the initial residual and identity mapping techniques. We showed that a deeper architecture (up to eight layers) allows significant performance improvement over other sequence-based and structure-based methods by more than 12.5% and 10.5% on AUPRC and MCC, respectively. Further analyses indicated that the predicted interacting sites by GraphPPIS are more spatially clustered and closer to the native ones even when false-positive predictions are made. The results highlight the importance of capturing spatially neighboring residues for interacting site prediction.

Availability and implementation

The datasets, the pre-computed features, and the source codes along with the pre-trained models of GraphPPIS are available at https://github.com/biomed-AI/GraphPPIS. The GraphPPIS web server is freely available at https://biomed.nscc-gz.cn/apps/GraphPPIS.

Supplementary information

Supplementary data are available at Bioinformatics online.
Learning sparse log-ratios for high-throughput sequencing data
Authors: Gordon-Rodriguez Elliott , Quinn Thomas P , Cunningham John P
Published: September 2021

Motivation

The automatic discovery of sparse biomarkers that are associated with an outcome of interest is a central goal of bioinformatics. In the context of high-throughput sequencing (HTS) data, and compositional data (CoDa) more generally, an important class of biomarkers are the log-ratios between the input variables. However, identifying predictive log-ratio biomarkers from HTS data is a combinatorial optimization problem, which is computationally challenging. Existing methods are slow to run and scale poorly with the dimension of the input, which has limited their application to low- and moderate-dimensional metagenomic datasets.

Results

Building on recent advances from the field of deep learning, we present CoDaCoRe, a novel learning algorithm that identifies sparse, interpretable and predictive log-ratio biomarkers. Our algorithm exploits a continuous relaxation to approximate the underlying combinatorial optimization problem. This relaxation can then be optimized efficiently using the modern ML toolbox, in particular, gradient descent. As a result, CoDaCoRe runs several orders of magnitude faster than competing methods, all while achieving state-of-the-art performance in terms of predictive accuracy and sparsity. We verify the outperformance of CoDaCoRe across a wide range of microbiome, metabolite and microRNA benchmark datasets, as well as a particularly high-dimensional dataset that is outright computationally intractable for existing sparse log-ratio selection methods.

Availability and implementation

The CoDaCoRe package is available at https://github.com/egr95/R-codacore. Code and instructions for reproducing our results are available at https://github.com/cunningham-lab/codacore.

Supplementary information

Supplementary data are available at Bioinformatics online.
MR-Corr2: a two-sample Mendelian randomization method that accounts for correlated horizontal pleiotropy using correlated instrumental variants
Authors: Cheng Qing , Qiu Tingting , Chai Xiaoran , Sun Baoluo , Xia Yingcun , Shi Xingjie , Liu Jin
Published: September 2021

Motivation

Mendelian randomization (MR) is a valuable tool to examine the causal relationships between health risk factors and outcomes from observational studies. Along with the proliferation of genome-wide association studies, a variety of two-sample MR methods for summary data have been developed to account for horizontal pleiotropy (HP), primarily based on the assumption that the effects of variants on exposure (γ) and HP (α) are independent. In practice, this assumption is too strict and can be easily violated because of the correlated HP.

Results

To account for this correlated HP, we propose a Bayesian approach, MR-Corr2, that uses the orthogonal projection to reparameterize the bivariate normal distribution for γ and α, and a spike-slab prior to mitigate the impact of correlated HP. We have also developed an efficient algorithm with paralleled Gibbs sampling. To demonstrate the advantages of MR-Corr2 over existing methods, we conducted comprehensive simulation studies to compare for both type-I error control and point estimates in various scenarios. By applying MR-Corr2 to study the relationships between exposure–outcome pairs in complex traits, we did not identify the contradictory causal relationship between HDL-c and CAD. Moreover, the results provide a new perspective of the causal network among complex traits.

Availability and implementation

The developed R package and code to reproduce all the results are available at https://github.com/QingCheng0218/MR.Corr2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Integrating genome-scale metabolic modelling and transfer learning for human gene regulatory network reconstruction
Authors: Pio Gianvito , Mignone Paolo , Magazzù Giuseppe , Zampieri Guido , Ceci Michelangelo , Angione Claudio
Published: September 2021

Motivation

Gene regulation is responsible for controlling numerous physiological functions and dynamically responding to environmental fluctuations. Reconstructing the human network of gene regulatory interactions is thus paramount to understanding the cell functional organization across cell types, as well as to elucidating pathogenic processes and identifying molecular drug targets. Although significant effort has been devoted towards this direction, existing computational methods mainly rely on gene expression levels, possibly ignoring the information conveyed by mechanistic biochemical knowledge. Moreover, except for a few recent attempts, most of the existing approaches only consider the information of the organism under analysis, without exploiting the information of related model organisms.

Results

We propose a novel method for the reconstruction of the human gene regulatory network, based on a transfer learning strategy that synergically exploits information from human and mouse, conveyed by gene-related metabolic features generated in silico from gene expression data. Specifically, we learn a predictive model from metabolic activity inferred via tissue-specific metabolic modelling of artificial gene knockouts. Our experiments show that the combination of our transfer learning approach with the constructed metabolic features provides a significant advantage in terms of reconstruction accuracy, as well as additional clues on the contribution of each constructed metabolic feature.

Availability and implementation

The method, the datasets and all the results obtained in this study are available at: https://doi.org/10.6084/m9.figshare.c.5237687.

Supplementary information

Supplementary data are available at Bioinformatics online.
SplicingFactory—splicing diversity analysis for transcriptome data
Authors: Dankó Benedek , Szikora Péter , Pór Tamás , Szeifert Alexa , Sebestyén Endre
Published: September 2021

Motivation

Alternative splicing contributes to the diversity of RNA found in biological samples. Current tools investigating patterns of alternative splicing check for coordinated changes in the expression or relative ratio of RNA isoforms where specific isoforms are up- or down-regulated in a condition. However, the molecular process of splicing is stochastic and changes in RNA isoform diversity for a gene might arise between samples or conditions. A specific condition can be dominated by a single isoform, while multiple isoforms with similar expression levels can be present in a different condition. These changes might be the result of mutations, drug treatments or differences in the cellular or tissue environment. Here, we present a tool for the characterization and analysis of RNA isoform diversity using isoform level expression measurements.

Results

We developed an R package called SplicingFactory, to calculate various RNA isoform diversity metrics, and compare them across conditions. Using the package, we tested the effect of RNA-seq quantification tools, quantification uncertainty, gene expression levels and isoform numbers on the isoform diversity calculation. We analyzed a set of CD34+ hematopoietic stem cells and myelodysplastic syndrome samples and found a set of genes whose isoform diversity change is associated with SF3B1 mutations.

Availability and implementation

The SplicingFactory package is freely available under the GPL-3.0 license from Bioconductor for the Windows, MacOS and Linux operating systems (https://www.bioconductor.org/packages/release/bioc/html/SplicingFactory.html).

Supplementary information

Supplementary data are available at Bioinformatics online.
VeloViz: RNA velocity-informed embeddings for visualizing cellular trajectories
Authors: Atta Lyla , Sahoo Arpan , Fan Jean
Published: September 2021

Motivation

Single-cell transcriptomics profiling technologies enable genome-wide gene expression measurements in individual cells but can currently only provide a static snapshot of cellular transcriptional states. RNA velocity analysis can help infer cell state changes using such single-cell transcriptomics data. To interpret these cell state changes inferred from RNA velocity analysis as part of underlying cellular trajectories, current approaches rely on visualization with principal components, t-distributed stochastic neighbor embedding and other 2D embeddings derived from the observed single-cell transcriptional states. However, these 2D embeddings can yield different representations of the underlying cellular trajectories, hindering the interpretation of cell state changes.

Results

We developed VeloViz to create RNA velocity-informed 2D and 3D embeddings from single-cell transcriptomics data. Using both real and simulated data, we demonstrate that VeloViz embeddings are able to capture underlying cellular trajectories across diverse trajectory topologies, even when intermediate cell states may be missing. By considering the predicted future transcriptional states from RNA velocity analysis, VeloViz can help visualize a more reliable representation of underlying cellular trajectories.

Availability and implementation

Source code is available on GitHub (https://github.com/JEFworks-Lab/veloviz) and Bioconductor (https://bioconductor.org/packages/veloviz) with additional tutorials at https://JEF.works/veloviz/. Datasets used can be found on Zenodo (https://doi.org/10.5281/zenodo.4632471).

Supplementary information

Supplementary data are available at Bioinformatics online.
Evolutionary drivers of morphological differentiation among three bottlenose dolphin lineages,Tursiopsspp. (Delphinidae), in the northwest Indian Ocean utilizing linear and geometric morphometric techniques
Authors: Gray Howard , van Waerebeek Koen , Owen Joseph , Collins Tim , Minton Gianna , Ponnampalam Louisa , Willson Andrew , Baldwin Robert , Hoelzel A Rus
Published: September 2021

Local adaptation and adaptive radiations are typically associated with phenotypic variation suited to alternative environments. In the marine environment, the nature of relevant ecological or environmental transitions is poorly understood, especially for highly mobile species. Here we compare three genetic lineages in the genus Tursiops (bottlenose dolphins), using linear measurements and geometric morphometric techniques, in the context of environmental variation in the northwest Indian Ocean. Cranial morphology was clearly differentiated comparing Tursiops truncatus and Tursiops aduncus, while a recently discovered genetic lineage, found in the Arabian Sea, was morphologically most similar to T. aduncus from the same region, but distinct for various measures, particularly metrics associated with the lateral dimension of the skull. The extent of divergence between T. truncatus and T. aduncus compared to differences between the T. aduncus lineages is consistent with the recent phylogeny for these species. Therefore, with the corroboration of genetic and morphological inference, we propose two conservation units of T. aduncus be recognized in the region at a sub-specific level so that their conservation can be managed effectively. We consider possible evolutionary mechanisms associated with regional habitat characteristics and the exploitation of distinct prey resources.
Treatment and long-term outcome of breast cancer in very young women: nationwide population-based study
Authors: Chen L -J , Chang Y -J , Chang Y -J
Published: September 2021

Background

The study aimed to assess the correlation between long-term survival and treatment in very young women with breast cancer.

Methods

Data on women with breast cancer were retrieved from the Taiwan Cancer Registry between 2004 and 2014. Patients who did not undergo surgery or who had stage 0 or IV disease were excluded. Survival analysis was conducted. The participants were divided into very young (20–29.9 years), young (30–39.9 years), and adult (40–50.0 years) groups.

Results

Among 104 115 women, 24 474 (572 very young, 5565 young, and 18 337 adult) were eligible for the study. Median follow-up was 79.5 (range 24–158) months. The mortality rates in the very young, young, and adult groups were 12.9, 10.0, and 8.2 per cent respectively (P < 0.001). Very young patients had higher histological grade, unfavourable subtype, higher TNM stage, and received more breast-conserving surgery (BCS). Kaplan–Meier survival analysis showed that very young patients had the poorest long-term survival. Very young patients with stage II disease had the worst prognosis. In the multivariable regression model, radiotherapy was associated with decreased local recurrence but not with improved overall, cancer-specific, or disease-free survival for stage II disease in the very young group. Surgery type and chemotherapy were not associated with significant improvement in overall survival.

Conclusion

Very young patients with stage II disease had poor long-term outcomes. BCS had no detrimental effects on long-term outcomes.
Decision making in emergency laparotomy: the role of predicted life expectancy
Authors: Choong J X , McIlveen E , Quasim T , Moug S J
Published: September 2021

Introduction

Increasing numbers of older patients are undergoing emergency laparotomy (EL). They are at increased risk of adverse outcomes, making the shared decision on whether to operate challenging. This retrospective cohort study aimed to assess the role of age and life-expectancy predictions on short- and long-term survival in patients undergoing EL.

Methods

All patients who underwent EL at one hospital in the West of Scotland between March 2014 to December 2016 were included. Clinical parameters were collected, and patients were followed up to allow reporting of 30-, 60- and 90-day and 1-year mortality rates. Period life expectancy was used to stratify patients into below life expectancy (bLEP) and at-or-above life expectancy (aLEP) groups at presentation. Remaining life expectancy was used to calculate the net years of life gained (NYLG).

Results

Some 462 patients underwent EL: 20 per cent in the aLEP group. These patients were older (P < 0.001), had more co-morbidities (P < 0.001) and were high risk on P-POSSUM scoring (P = 0.008). The 30-, 60- and 90-day and 1-year mortality rates were 11, 14, 16 and 23 per cent respectively. Advanced age (P = 0.011) and high ASA score (P = 0.004) and P-POSSUM score (P < 0.001) were independent predictors of death at 1 year on multivariable analysis. The cohort NYLG were 19.2 years. Comparing patients aged less than 70 with those aged 70 years or older, the NYLG were 25.9 versus 5.5 years. Comparing bLEP and aLEP, the NYLG were 22.2 versus 4.4 years. In patients aged 70 years and older, NYLG decreased by more than half in patients with co-morbidities (ASA score 3,4,5) (9.3 versus 4.3 years).

Conclusion

Discussions around long-term outcomes after emergency surgery remain difficult. Although age is an influencing factor, predicted life expectancy alone does not provide additional value to shared decision making.
Organ preservation following short-course radiotherapy for rectal cancer
Authors: Nilsson Per J , Ahlberg Madelene , Kordnejad Shahrzad , Holm Torbjörn , Martling Anna
Published: September 2021

Background

Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients.

Methods

Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated.

Results

Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups.

Conclusion

In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.
‘My Contributions Made a Significant Difference’: Young Carers’ Reflections on Their Participation in Social Work Admissions
Authors: Newman Andrea , Carey Bridgit , Kinney Malcolm
Published: September 2021

Whilst the participation of service users and carers (SUCs) in Social Work admissions (SWAs) has significantly developed over the past decades, concerns have been raised about the tokenistic nature of SUC involvement (Barnes, D., Carpenter, J. and Bailey, D. (2000) ‘Partnerships with service users in interprofessinal education for community mental health: A case study’, Journal of Interprofessional Care, 14(2), pp. 189–200) particularly in relation to young people (YP). Liverpool John Moores University (LJMU) in partnership with Barnardo’s Action with Young Carers Liverpool have (BAWYC) worked to develop meaningful participation for YP in SWA. In this article, we discuss our approach to YPs’ participation, exploring their experiences of involvement. Using a co-production approach, drawing on participatory action research methodology, we utilise in-depth interviews from a purposive sample of young carers (YCs) to ask questions about the nature of YPs’ participation including: How meaningful they consider their involvement; what are the outcomes and benefits and what are the continuing barriers? Adopting a reflective thematic analysis, research findings indicate that YCs feel valued and respected in their SWA role, and surprised at the level of involvement and decision making ascribed to them. They report personal development and feelings of self-worth and increased confidence, helping them to consider their own futures in a more aspirational way.
Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis
Authors: Salman Mootaz M , Kitchen Philip , Halsey Andrea , Wang Marie Xun , Törnroth-Horsefield Susanna , Conner Alex C , Badaut Jerome , Iliff Jeffrey J , Bill Roslyn M
Published: September 2021

Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed in astrocytes. In the CNS, it is enriched in astrocyte endfeet, at synapses, and at the glia limitans, where it mediates water exchange across the blood–spinal cord and blood–brain barriers (BSCB/BBB), and controls cell volume, extracellular space volume, and astrocyte migration. Perivascular enrichment of AQP4 at the BSCB/BBB suggests a role in glymphatic function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease.