bluuebunny/crossref_metadata_2025 huggingface dataset:
Few-shot link prediction with meta-learning for temporal knowledge graphs
Authors: Zhu Lin , Xing Yizong , Bai Luyi , Chen Xiwen
Published: March 2023

With the deepening of the research on knowledge graph embedding, temporal knowledge graphs (TKGs), which are dynamic changes over time, have gradually gained the attention of researchers. Although some TKG-embedding models have been proposed, they did not perform well for certain relationships with insufficient samples, since they all require tremendous training samples. Thus, few-shot link prediction tasks, namely predicting new relation-specific quadruples by observing only a few samples, are still very challenging. In this paper, a method named meta-reasoning for TKGs (MetaRT) is proposed to solve this universal but challenging problem. MetaRT works by extracting the meta-information of a specific relation and updating it quickly, so that the model can learn the most critical information in TKG swiftly and independently. In the meantime, temporal information can be managed well by a TKG learner. Finally, through a large number of experiments, it shows that MetaRT outperforms other existing TKG-embedding models on the problem of few-shot learning.
Opposition-based learning boosted orca predation algorithm with dimension learning: a case study of multi-degree reduction for NURBS curves
Authors: Hu Gang , Jing Wenlong , Wei Guo , Abbas Muhammad
Published: March 2023

The approximate degree reduction of ball non-uniform rational B-splines (NURBS) curves is a pivotal and knotty technique in computer-aided design/computer-aided manufacture. As we all know, the multi-degree reduction of NURBS ones is a mathematical optimization problem that a swarm intelligence algorithm can deal with. This paper uses an improved orca predation algorithm (IOPA) to accomplish the optimal multi-degree reduction of NURBS curves. Firstly, by incorporating a dimension learning strategy and opposition-based learning strategy into the orca predation algorithm (OPA), an IOPA is developed to increase the population diversity and enhance its capability of jumping out of the local minima. Secondly, the superiority of the proposed IOPA is comprehensively verified by comparing it with the original OPA and numerous celebrated and newly developed algorithms on the IEEE Congress on Evolutionary Computation (CEC) 2014 test suite and IEEE CEC2017 benchmark functions, respectively. Meanwhile, the practicability of IOPA is also highlighted by solving three real-world engineering design problems. Furthermore, statistical testing of IOPA has been conducted to validate its significance. Finally, the optimization model of multi-degree reduction for NURBS curves is established by minimizing the distance between the original curve and the approximate curve. The IOPA is utilized to solve the optimization model, and the optimal approximate NURBS curves are obtained. Some representative numerical examples illustrate the ability of the proposed IOPA to effectively solve the multi-degree reduction problem of NURBS curves in terms of precision, robustness, and convergence characteristics.
Hierarchical reinforcement learning from competitive self-play for dual-aircraft formation air combat
Authors: Kong Wei-ren , Zhou De-yun , Zhou Ying , Zhao Yi-yang
Published: March 2023

The recent development of technology helps in the revolutionary war and it controls the war which is influenced by brilliant planning. The maneuver aircraft of intelligent algorithm aids the pilot to decide the particular position on the battlefield. Nowadays the hardware components of radar and missiles are widely used and the beyond visual range is the most popular method applied in air combat. The introduction of close-range air combat maneuver decisions generates the attention of researchers in artificial intelligence. Most of the existing methods are based on autonomous aircraft focused in air combat scenario but manual air combats are widely applied in dual aircraft. Based on the factors mentioned above, a novel hierarchical maneuver decision architecture is applied to a dual-aircraft close-range air combat scenario. Subsequently, the soft actor-critic algorithm is merged with competitive self-play which integrates the knowledge of sub-strategies. Further, the reinforcement learning technique is employed to achieve an approximate Nash equilibrium master strategy. The experimental results show that the hierarchical architecture exhibits good performance, symmetry, and robustness. The research generates a solution for intelligent formation of air combat in the future and guidance for manned or unmanned aircraft cooperative combat.
In Between Breaths: Memories, Stories, and Otherwise Design Histories
Authors: Cheang Sarah , Irani Katie , Rezende Livia , Suterwalla Shehnaz
Published: March 2023

Decolonial approaches foreground the necessity for design historians to rethink their methodologies and terms of debate to recognize the impact of colonial legacies. Only then is it possible to make changes toward social and cognitive justice. This piece explores new models for working collectively with history and memory across oral registers to include the colloquial and moments of pause, of taking breath.

In mid-2020, four design historians teamed up to develop experimental, multimedia methods of working to explore new critical design histories. By using “otherwise” methods to look, listen, and read closely, this piece foregrounds the making of space for new interpretations of thinking and writing. The tensions between memories, stories, and histories are interpreted and challenged using concepts such as breath, voice, palimpsest, circle and rhythm. Exploring translation, opacity, embodiment, positionality, and nonlinearity emerged as crucial to questioning the terms under which design history can be transformed.
U-net-based pseudoseismic imaging for the short-offset transient electromagnetic method
Authors: Zhao Yang , Wu Xin , Chen Weiying
Published: March 2023

Short-offset transient electromagnetic (SOTEM) is an innovation of the artificial-source electromagnetic method, and detection is conducted in the near-source area using an electromagnetic formation wave so that the signal has strong strength and large bandwidth. Inspired by the parallelism of the propagation of seismic body waves and EM formation waves, this paper intends to implement pseudoseismic imaging (PSI) on SOTEM data to give play to the high resolution of SOTEM. Traditionally, to perform the wave-field transform (WFT), a set of ill-posed linear equations needs to be solved and the solving process has strong ambiguity and instability. This paper presents a new method for performing WFT based on U-Net, and a nonlinear mapping from the EM diffusion field to the pseudoseismic wave field under the same velocity model is established by training the network. To eliminate the error that might result when the time‒depth transform is conducted for the wave-field record, another U-Net is used to transform the wave-field record into a depth-offset profile to accomplish the whole PSI process for SOTEM. Simulation and measured data are used to validate the effect of the networks, and the results indicate that this approach is highly feasible, thus providing a new strategy for using SOTEM to detect sedimentary strata.
From Stosch through Carafa to Hamilton and the British Museum
Authors: Gołyźniak Paweł
Published: March 2023

This article discusses several rare Egyptian scarabs and Near Eastern cylinder seals, together with their visual documentation in the form of drawings made for Philipp von Stosch (1691–1757) in the 1720s and 1730s. These records have proved important in research on the provenance of the original objects, which entered the British Museum in 1772 from the cabinet of incised gems belonging to Sir William Hamilton (1730–1803). They also demonstrate that, in his collecting and studies of glyptic art, Stosch not only focused on Graeco-Roman gems but tried to cover all aspects of glyptics, despite the limited availability of some varieties. The drawings deliver proof of the claim that he regarded Egyptian scarabs and Near Eastern cylinder seals as the most ancient glyptic products and began work on the chronological systematization of engraved gems well before Johann Joachim Winckelmann (1717–1768) presented his vision of the development of ancient art.
Interpolations in the Mahābhārata: The Attempted Disrobing Episode
Authors: Jategaonkar Arun Vinayak , Jategaonkar Vasanti Arun
Published: March 2023

The present paper is about originality and contents of a well-known episode in the Mahābhārata: The episode in the aftermath of the first dicing contest from the Sabhāparvan in which Duḥśāsana, ordered by Karṇa, attempts to disrobe Draupadī in the Kuru Sabhā. The paper shows that the episode in question is not only interpolated in the text of the Mahābhārata relatively recently; it was interpolated in two separate steps. The first step was the interpolation of the version in which, as Duḥśāsana started to disrobe Draupadī, a miracle took place and Duḥśāsana, try as he might, was unable to disrobe her; the second step was the interpolation of Draupadī’s prayer and Kr̥ṣṇa’s intervention from the popular version of that episode as the source of that miracle. The paper also shows that the Critical Edition of the Mahābhārata contains much more data supporting the preceding conclusions than has been hitherto recognised. The paper explores the implications of these findings for the basic rules used by the editors of the critical edition of the Mahābhārata to construct its critically reconstituted text.
Blockchain and its Applications: A Conceptual Legal Primer
Authors: Buckley Ross P , Didenko Anton N , Trzecinski Mia
Published: March 2023

Blockchain is a potent buzzword and a potentially transformative technology. Diverse businesses are looking to leverage this technology to reap its alleged benefits of increased efficiency, reduced costs, enhanced transparency, and improved traceability. Yet, significant confusion persists about the structure, utility, and applicability of blockchain technology. A clear understanding of what blockchain is and how it works is especially important for lawyers advising clients on the applications that use, or purport to use, it. This article aims to assist lawyers and regulators by providing conceptual clarity about what blockchain is, how it works, and its main use cases. These use cases include smart contracts, cryptoassets, and some central bank digital currencies. These applications may transform business practices, or even entire monetary and payment systems, so conceptual clarity among lawyers will only become more vital.
Deciphering the localization and trajectory of human natural killer cell development
Authors: Hegewisch-Solloa Everardo , Nalin Ansel P , Freud Aharon G , Mace Emily M
Published: March 2023

Innate immune cells represent the first line of cellular immunity, comprised of both circulating and tissue-resident natural killer cells and innate lymphoid cells. These innate lymphocytes arise from a common CD34+ progenitor that differentiates into mature natural killer cells and innate lymphoid cells. The successive stages in natural killer cell maturation are characterized by increased lineage restriction and changes to phenotype and function. Mechanisms of human natural killer cell development have not been fully elucidated, especially the role of signals that drive the spatial localization and maturation of natural killer cells. Cytokines, extracellular matrix components, and chemokines provide maturation signals and influence the trafficking of natural killer cell progenitors to peripheral sites of differentiation. Here we present the latest advances in our understanding of natural killer and innate lymphoid cell development in peripheral sites, including secondary lymphoid tissues (i.e. tonsil). Recent work in the field has provided a model for the spatial distribution of natural killer cell and innate lymphoid cell developmental intermediates in tissue and generated further insights into the developmental niche. In support of this model, future studies using multifaceted approaches seek to fully map the developmental trajectory of human natural killer cells and innate lymphoid cells in secondary lymphoid tissues.
The influence of lichen sclerosus on women’s sexual health from a biopsychosocial perspective: a mixed methods study
Authors: Caspersen Irene S , Højgaard Astrid , Laursen Birgitte S
Published: March 2023

Background

Women with lichen sclerosus (LS) may suffer sexually because of dyspareunia, fissures, and introital narrowing. However, the literature remains limited on the biopsychosocial aspects of LS and its impact on sexual health.

Aim

To examine the biopsychosocial aspects and impact of LS on the sexual health of Danish women with vulvar LS.

Methods

The study was conducted with a mixed methods approach, including women with LS from a Danish patient association. The quantitative sample consisted of 172 women who completed a cross-sectional online survey that included 2 validated questionnaires: the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS). The qualitative sample consisted of 5 women with LS who volunteered for audiotaped, individual, semistructured interviews.

Outcomes

This mixed methods study combined data from 2 quantitative questionnaires (FSFI and FSDS) with qualitative interviews to achieve a comprehensive insight into the biopsychosocial aspects of sexual health in women living with LS.

Results

The sexual function of women with LS was considerably affected, with FSFI scores below the cutoff value of 26.55, indicating a risk of sexual dysfunction. On average, 75% of the women were sexually distressed, with a total FSDS score of 25.47. Furthermore, 68% of the sexually active women were considerably affected in terms of sexual function and sexual distress, thus meeting international criteria for sexual dysfunction. However, a negative impact on sexual function was not always related to sexual distress and vice versa. The qualitative analysis identified 4 overarching themes: (1) decrease in or loss of sexual activity, (2) interference with relationship dynamics, (3) importance of sex and intimacy – loss and restoration, and (4) worries about sexual insufficiency.

Clinical Implications

Insight into the influence of LS on sexual health is important for health care professionals, including doctors, nurses, sex therapists, and physiotherapists, to provide the best guidance, support, and management for women with LS.

Strengths and Limitations

The strengths of the study are its use of a mixed methods design and the inclusion of sexual function and sexual distress. A limitation is related to the properties of the FSFI regarding women with no sexual activity.

Conclusions

LS has a considerable influence on women’s sexual health in terms of sexual function and sexual distress, as supported by quantitative and qualitative measures. Our understanding of the complex interactions among sexual activity, intimate relations, and causes of psychological distress has been enriched.
Self-Fashioning Illusions: Twinship, Subjectivity, and Neo-Victorianism in Christopher Priest’s  The Prestige
Authors: Ioannidou Elisavet
Published: March 2023

Examining the conflicting approaches to the fragmentation of the self and the feasibility of self-awareness featured in Christopher Priest’s novel The Prestige (1995), this article reflects on the evaluation, and subsequent reinvention, of the Victorian era in the genre commonly known as neo-Victorian fiction. Alfred Borden, the novel’s Victorian protagonist, fashions himself as a unique and unified individual even though his identity is, in fact, composite and alternatingly shared between twin brothers. In contrast, Andrew Westley, Borden’s twentieth-century descendant, experiences an instinctive sense of division through which he rationalizes his life. Featured in temporally distinct storylines, these conflicting perspectives reflect the tensions at work in the neo-Victorian return to the Victorian past. Silencing multiplicity and negating fragmentation, the Victorian characters echo scholarly objections to the use of the term ‘Victorian’: its apparent assertion of coherence and homogeneity when it is actually called to signify an extremely diverse historical period. Conversely, by means of the twentieth-century protagonist’s need to comprehend and embrace division, a need which is fulfilled through Andrew’s familiarization with and acceptance of his past, the novel acknowledges the multivalence of the ‘Victorian’ and its indisputable connection to the present. Exploring Victorian and twentieth-century appreciations of subjectivity, The Prestige sheds light into neo-Victorianism’s self-fashioning strategies, raising the question whether and to what extent neo-Victorian reconfigurations of the Victorian era (re)discover the past, or operate on our potentially misleading preconceptions about the nineteenth century.
Polishing De Novo Nanopore Assemblies of Bacteria and Eukaryotes With FMLRC2
Authors: Mak Q X Charles , Wick Ryan R , Holt James Matthew , Wang Jeremy R
Published: March 2023

As the accuracy and throughput of nanopore sequencing improve, it is increasingly common to perform long-read first de novo genome assemblies followed by polishing with accurate short reads. We briefly introduce FMLRC2, the successor to the original FM-index Long Read Corrector (FMLRC), and illustrate its performance as a fast and accurate de novo assembly polisher for both bacterial and eukaryotic genomes.
Droplet microfluidic chip-ICP–MS-based single-cell analysis for study of cellular behavior of macrophages to thimerosal
Authors: Ma Junrong , He Man , Chen Beibei , Hu Bin
Published: March 2023

Thimerosal (THI) is widely used as an antimicrobial preservative, but can hydrolyze to ethylmercury, causing potentially neurotoxicity. In this work, a THP-1 cell line was used to investigate the biological behavior of THI. An on-line droplet microfluidic chip system combined with time-resolved inductively coupled plasma mass spectrometry was used to quantify Hg in single THP-1 cells. The cellular uptake and elimination behaviors of THI were studied, and the toxicity of THI in terms of redox balance was discussed. The results showed that a small number of cells (<5%) exhibited a high uptake content (>200 fg/cell) for THI, and most of the cells (68.8–85.8% for different exposure groups at 25 h) exhibited a relatively low uptake content (<20 fg/cell). After stopping exposure to THI, the cells showed an elimination process for Hg, which was rapid in the first several hours and gradually slowed down. When the elimination time was 25 h, 7.4–26.3% of the cells in different exposure groups still contained a detectable amount of Hg (>2 fg/cell), indicating Hg could not be eliminated completely, which may cause cumulative toxicity to macrophages. Moreover, it was found that exposure to THI even at 50 ng/mL can cause cellular oxidative stress behavior, leading to an increase in reactive oxygen species level and a decrease in glutathione level. This trend would continue for a period of time after stopping THI exposure. With the elimination of Hg, the redox balance of cells showed a tendency to stabilize and restore, but cannot be restored to normal status, indicating a long-term chronic toxicity of THI to THP-1 cells.
Fitness functions for RNA structure design
Authors: Ward Max , Courtney Eliot , Rivas Elena
Published: March 2023

An RNA design algorithm takes a target RNA structure and finds a sequence that folds into that structure. This is fundamentally important for engineering therapeutics using RNA. Computational RNA design algorithms are guided by fitness functions, but not much research has been done on the merits of these functions. We survey current RNA design approaches with a particular focus on the fitness functions used. We experimentally compare the most widely used fitness functions in RNA design algorithms on both synthetic and natural sequences. It has been almost 20 years since the last comparison was published, and we find similar results with a major new result: maximizing probability outperforms minimizing ensemble defect. The probability is the likelihood of a structure at equilibrium and the ensemble defect is the weighted average number of incorrect positions in the ensemble. We find that maximizing probability leads to better results on synthetic RNA design puzzles and agrees more often than other fitness functions with natural sequences and structures, which were designed by evolution. Also, we observe that many recently published approaches minimize structure distance to the minimum free energy prediction, which we find to be a poor fitness function.
Structural and functional insights into the activation of the dual incision activity of UvrC, a key player in bacterial NER
Authors: Seck Anna , De Bonis Salvatore , Stelter Meike , Ökvist Mats , Senarisoy Müge , Hayek Mohammad Rida , Le Roy Aline , Martin Lydie , Saint-Pierre Christine , Silveira Célia M , Gasparutto Didier , Todorovic Smilja , Ravanat Jean-Luc , Timmins Joanna
Published: March 2023

Bacterial nucleotide excision repair (NER), mediated by the UvrA, UvrB and UvrC proteins is a multistep, ATP-dependent process, that is responsible for the removal of a very wide range of chemically and structurally diverse DNA lesions. DNA damage removal is performed by UvrC, an enzyme possessing a dual endonuclease activity, capable of incising the DNA on either side of the damaged site to release a short single-stranded DNA fragment containing the lesion. Using biochemical and biophysical approaches, we have probed the oligomeric state, UvrB- and DNA-binding abilities and incision activities of wild-type and mutant constructs of UvrC from the radiation resistant bacterium, Deinococcus radiodurans. Moreover, by combining the power of new structure prediction algorithms and experimental crystallographic data, we have assembled the first model of a complete UvrC, revealing several unexpected structural motifs and in particular, a central inactive RNase H domain acting as a platform for the surrounding domains. In this configuration, UvrC is maintained in a ‘closed’ inactive state that needs to undergo a major rearrangement to adopt an ‘open’ active state capable of performing the dual incision reaction. Taken together, this study provides important insight into the mechanism of recruitment and activation of UvrC during NER.
Proteomic analyses reveal new features of the box H/ACA RNP biogenesis
Authors: Schlotter Florence , Mérouani Salim , Flayac Justine , Kogey Valentyne , Issa Amani , Dodré Maxime , Huttin Alexandra , Branlant Christiane , Bertrand Edouard , Labialle Stéphane , Vandermoere Franck , Verheggen Céline , Massenet Séverine
Published: March 2023

The conserved H/ACA RNPs consist of one H/ACA RNA and 4 core proteins: dyskerin, NHP2, NOP10, and GAR1. Its assembly requires several assembly factors. A pre-particle containing the nascent RNAs, dyskerin, NOP10, NHP2 and NAF1 is assembled co-transcriptionally. NAF1 is later replaced by GAR1 to form mature RNPs. In this study, we explore the mechanism leading to the assembly of H/ACA RNPs. We performed the analysis of GAR1, NHP2, SHQ1 and NAF1 proteomes by quantitative SILAC proteomic, and analyzed purified complexes containing these proteins by sedimentation on glycerol gradient. We propose the formation of several distinct intermediate complexes during H/ACA RNP assembly, notably the formation of early protein-only complexes containing at least the core proteins dyskerin, NOP10, and NHP2, and the assembly factors SHQ1 and NAF1. We also identified new proteins associated with GAR1, NHP2, SHQ1 and NAF1, which can be important for box H/ACA assembly or function. Moreover, even though GAR1 is regulated by methylations, the nature, localization, and functions of these methylations are not well known. Our MS analysis of purified GAR1 revealed new sites of arginine methylations. Additionally, we showed that unmethylated GAR1 is correctly incorporated in H/ACA RNPs, even though with less efficiency than methylated ones.
Recent advancements in the structural biology of human telomerase and their implications for improved design of cancer therapeutics
Authors: Welfer Griffin A , Freudenthal Bret D
Published: March 2023

Telomerase is a specialized reverse transcriptase that synthesizes telomeric repeats at the ends of linear chromosomes. Telomerase is transiently expressed in germ and stem cells, but nearly all somatic cells silence it after differentiating. However, the vast majority of cancer cells reactivate and constitutively express telomerase to maintain replicative immortality. Because of this, telomerase has remained a promising broad-spectrum chemotherapeutic target for over 30 years. However, various challenges associated with obtaining high-resolution structural data for telomerase have limited the development of rationally designed structure-based therapeutics. Various techniques and model systems have been utilized to advance our understanding of the structural biology of telomerase. In particular, multiple high-resolution cryogenic electron microscopy (cryo-EM) structures published within the past few years have revealed new components of the telomerase complex with near atomic resolution structural models. Additionally, these structures have provided details for how telomerase is recruited to telomeres and its mechanism of telomere synthesis. With these new pieces of evidence, and the promising outlook for future refinements to our current models, the possibility of telomerase specific chemotherapeutics is becoming more tangible than ever. This review summarizes these recent advancements and outlines outstanding questions in the field.
ICI efficacy information portal: a knowledgebase for responder prediction to immune checkpoint inhibitors
Authors: Chen Jiamin , Rebibo Daniel , Cao Jianquan , Mok Simon Yat-Man , Patel Neel , Tseng Po-Cheng , Zhang Zhenghao , Yip Kevin Y
Published: March 2023

Immune checkpoint inhibitors (ICIs) have led to durable responses in cancer patients, yet their efficacy varies significantly across cancer types and patients. To stratify patients based on their potential clinical benefits, there have been substantial research efforts in identifying biomarkers and computational models that can predict the efficacy of ICIs, and it has become difficult to keep track of all of them. It is also difficult to compare findings of different studies since they involve different cancer types, ICIs, and various other details. To make it easy to access the latest information about ICI efficacy, we have developed a knowledgebase and a corresponding web-based portal (https://iciefficacy.org/). Our knowledgebase systematically records information about latest publications related to ICI efficacy, predictors proposed, and datasets used to test them. All information recorded is checked carefully by a manual curation process. The web-based portal provides functions to browse, search, filter, and sort the information. Digests of method details are provided based on the original descriptions in the publications. Evaluation results of the effectiveness of the predictors reported in the publications are summarized for quick overviews. Overall, our resource provides centralized access to the burst of information produced by the vibrant research on ICI efficacy.
R-loops, type I topoisomerases and cancer
Authors: Saha Sourav , Pommier Yves
Published: March 2023

R-loops are abundant and dynamic structures ubiquitously present in human cells both in the nuclear and mitochondrial genomes. They form in cis in the wake of transcription complexes and in trans apart from transcription complexes. In this review, we focus on the relationship between R-loops and topoisomerases, and cancer genomics and therapies. We summarize the topological parameters associated with the formation and resolution of R-loops, which absorb and release high levels of genomic negative supercoiling (Sc-). We review the deleterious consequences of excessive R-loops and rationalize how human type IA (TOP3B) and type IB (TOP1) topoisomerases regulate and resolve R-loops in coordination with helicase and RNase H enzymes. We also review the drugs (topoisomerase inhibitors, splicing inhibitors, G4 stabilizing ligands) and cancer predisposing genes (BRCA1/2, transcription, and splicing genes) known to induce R-loops, and whether stabilizing R-loops and thereby inducing genomic damage can be viewed as a strategy for cancer treatment.
DELongSeq for efficient detection of differential isoform expression from long-read RNA-seq data
Authors: Hu Yu , Gouru Anagha , Wang Kai
Published: March 2023

Conventional gene expression quantification approaches, such as microarrays or quantitative PCR, have similar variations of estimates for all genes. However, next-generation short-read or long-read sequencing use read counts to estimate expression levels with much wider dynamic ranges. In addition to the accuracy of estimated isoform expression, efficiency, which measures the degree of estimation uncertainty, is also an important factor for downstream analysis. Instead of read count, we present DELongSeq, which employs information matrix of EM algorithm to quantify uncertainty of isoform expression estimates to improve estimation efficiency. DELongSeq uses random-effect regression model for the analysis of DE isoform, in that within-study variation represents variable precision in isoform expression estimation and between-study variation represents variation in isoform expression levels across samples. More importantly, DELongSeq allows 1 case versus 1 control comparison of differential expression, which has specific application scenarios in precision medicine (such as before versus after treatment, or tumor versus stromal tissues). Through extensive simulations and analysis of several RNA-Seq datasets, we show that the uncertainty quantification approach is computationally reliable, and can improve the power of differential expression (DE) analysis of isoforms or genes. In summary, DELongSeq allows for efficient detection of differential isoform/gene expression from long-read RNA-Seq data.
TiSA: TimeSeriesAnalysis—a pipeline for the analysis of longitudinal transcriptomics data
Authors: Lefol Yohan , Korfage Tom , Mjelle Robin , Prebensen Christian , Lüders Torben , Müller Bruno , Krokan Hans , Sarno Antonio , Alsøe Lene ,   CONSORTIUM LEMONAID, Berdal Jan-Erik , Sætrom Pål , Nilsen Hilde , Domanska Diana
Published: March 2023

Improved transcriptomic sequencing technologies now make it possible to perform longitudinal experiments, thus generating a large amount of data. Currently, there are no dedicated or comprehensive methods for the analysis of these experiments. In this article, we describe our TimeSeries Analysis pipeline (TiSA) which combines differential gene expression, clustering based on recursive thresholding, and a functional enrichment analysis. Differential gene expression is performed for both the temporal and conditional axes. Clustering is performed on the identified differentially expressed genes, with each cluster being evaluated using a functional enrichment analysis. We show that TiSA can be used to analyse longitudinal transcriptomic data from both microarrays and RNA-seq, as well as small, large, and/or datasets with missing data points. The tested datasets ranged in complexity, some originating from cell lines while another was from a longitudinal experiment of severity in COVID-19 patients. We have also included custom figures to aid with the biological interpretation of the data, these plots include Principal Component Analyses, Multi Dimensional Scaling plots, functional enrichment dotplots, trajectory plots, and complex heatmaps showing the broad overview of results. To date, TiSA is the first pipeline to provide an easy solution to the analysis of longitudinal transcriptomics experiments.
TIS Transformer: remapping the human proteome using deep learning
Authors: Clauwaert Jim , McVey Zahra , Gupta Ramneek , Menschaert Gerben
Published: March 2023

The correct mapping of the proteome is an important step towards advancing our understanding of biological systems and cellular mechanisms. Methods that provide better mappings can fuel important processes such as drug discovery and disease understanding. Currently, true determination of translation initiation sites is primarily achieved by in vivo experiments. Here, we propose TIS Transformer, a deep learning model for the determination of translation start sites solely utilizing the information embedded in the transcript nucleotide sequence. The method is built upon deep learning techniques first designed for natural language processing. We prove this approach to be best suited for learning the semantics of translation, outperforming previous approaches by a large margin. We demonstrate that limitations in the model performance are primarily due to the presence of low-quality annotations against which the model is evaluated against. Advantages of the method are its ability to detect key features of the translation process and multiple coding sequences on a transcript. These include micropeptides encoded by short Open Reading Frames, either alongside a canonical coding sequence or within long non-coding RNAs. To demonstrate the use of our methods, we applied TIS Transformer to remap the full human proteome.
Single-cell gene set enrichment analysis and transfer learning for functional annotation of scRNA-seq data
Authors: Franchini Melania , Pellecchia Simona , Viscido Gaetano , Gambardella Gennaro
Published: March 2023

Although an essential step, cell functional annotation often proves particularly challenging from single-cell transcriptional data. Several methods have been developed to accomplish this task. However, in most cases, these rely on techniques initially developed for bulk RNA sequencing or simply make use of marker genes identified from cell clustering followed by supervised annotation. To overcome these limitations and automatize the process, we have developed two novel methods, the single-cell gene set enrichment analysis (scGSEA) and the single-cell mapper (scMAP). scGSEA combines latent data representations and gene set enrichment scores to detect coordinated gene activity at single-cell resolution. scMAP uses transfer learning techniques to re-purpose and contextualize new cells into a reference cell atlas. Using both simulated and real datasets, we show that scGSEA effectively recapitulates recurrent patterns of pathways’ activity shared by cells from different experimental conditions. At the same time, we show that scMAP can reliably map and contextualize new single-cell profiles on a breast cancer atlas we recently released. Both tools are provided in an effective and straightforward workflow providing a framework to determine cell function and significantly improve annotation and interpretation of scRNA-seq data.
Perceptions of Illicit Tobacco Sources Following a Proposed Reduction in Tobacco Availability: A Qualitative Analysis of New Zealanders Who Smoke
Authors: Hoek Janet , Graham-DeMello Anna , Wilson Nick
Published: March 2023

Introduction

Tobacco companies claim that substantially reducing tobacco retail outlets in Aotearoa New Zealand will increase illicit tobacco trade and crime. However, we know little about whether people who smoke anticipate using illicit tobacco once this measure is implemented. Exploring current illicit tobacco use and expected market development would clarify the likely scale of this potential problem.

Aims and Methods

We undertook online in-depth interviews with 24 adults who smoke and explored their experiences of illicit tobacco, perceptions of illicit market growth once legal tobacco became less available, intentions to engage in this market, and potential measures that could curb illicit market development. We interpreted the data using a qualitative descriptive approach.

Results

Few participants had purchased illegally imported or stolen tobacco. While most did not know how to access illicit tobacco products, many expected illicit trade and crime would increase, if legal tobacco became difficult to access. While cheaper tobacco appealed to many, most perceived illicit supply routes as unsafe and saw products obtained via these sources as likely to be of poor quality. Few suggested measures to control illicit markets, though a minority called for social reforms to reduce poverty, which they thought fueled illegal practices.

Conclusions

Although illicit trade may appear to threaten new policy initiatives, participants’ limited knowledge of these markets and concerns regarding product safety suggest illegal tobacco may pose less of a threat than tobacco companies have claimed. Policy makers should not be deterred from reducing tobacco availability by industry arguments.

Implications

Although participants believed illicit trade would increase if the number of tobacco retailers was substantially reduced, few anticipated purchasing illegal tobacco. They viewed supply routes as unsafe and product quality as likely to be low. Industry predictions that illicit tobacco trade will grow if tobacco becomes less available do not reflect how people who smoke expect to engage with these markets and should not deter the introduction of retail reduction measures.
Risk of Coronavirus Disease 2019–Associated Pulmonary Aspergillosis Based on Corticosteroid Duration in Intensive Care Patients
Authors: Shah Meera , Reveles Kelly , Moote Rebecca , Hand Elizabeth , Kellogg III Dean , Attridge Rebecca L , Maselli Diego J , Gutierrez G Christina
Published: March 2023

Background

Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA.

Methods

This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Incidence of CAPA and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor in a logistic regression model.

Results

A total of 278 patients were included (n = 169 for ≤10 days’ steroid duration; n = 109 for >10 days). CAPA developed in 20 of 278 (7.2%) patients. Patients treated with >10 days of corticosteroid therapy had significantly higher incidence of CAPA (11.9% vs 4.1%; P = .0156), and steroid duration >10 days was independently associated with CAPA (odds ratio, 3.17 [95% confidence interval, 1.02–9.83]). Secondary outcomes including inpatient mortality (77.1% vs 43.2%; P < .0001), mechanical ventilation–free days at 28 days (0 vs 1.5; P < .0001), and secondary infections (44.9% vs 28.4% P = .0220) were worse in the >10 days cohort.

Conclusions

Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.
Geospatial Analysis of Time to Human Immunodeficiency Virus (HIV) Diagnosis and Adult HIV Testing Coverage Highlights Areas for Intervention in the US Southeast
Authors: Matthews Lynn T , Long Dustin M , Bassler John , Nassel Ariann , Levitan Emily B , Heath Sonya L , Rastegar Jeremiah , Pratt Madeline C , Kempf Mirjam-Collette
Published: March 2023

Background

In the United States (US), 44% of people with human immunodeficiency virus (PWH) live in the Southeastern census region; many PWH remain undiagnosed. Novel strategies to inform testing outreach in rural states with dispersed HIV epidemics are needed.

Methods

Alabama state public health HIV testing surveillance data from 2013 to 2017 were used to estimate time from infection to HIV diagnosis using CD4 T-cell depletion modeling, mapped to county. Diagnostic HIV tests performed during 2013–2021 by commercial testing entities were used to estimate HIV tests per 100 000 adults (aged 15–65 years), mapped to client ZIP Code Tabulation Area (ZCTA). We then defined testing “cold spots”: those with <10% adults tested plus either (1) within or bordering 1 of the 13 counties with HIV prevalence >400 cases per 100 000 population or (2) within a county with average time to diagnosis greater than the state average to inform testing outreach.

Results

Time to HIV diagnosis was a median of 3.7 (interquartile range [IQR], 0–9.2) years across Alabama, with a range of 0.06–12.25 years. Approximately 63% of counties (n = 42) had a longer time to diagnosis compared to national US estimates. Six hundred forty-three ZCTAs tested 17.3% (IQR, 10.3%–25.0%) of the adult population from 2013 to 2017. To prioritize areas for testing outreach, we generated maps to describe 47 areas of HIV-testing cold spots at the ZCTA level.

Conclusions

Combining public health surveillance with commercial testing data provides a more nuanced understanding of HIV testing gaps in a state with a rural HIV epidemic and identifies areas to prioritize for testing outreach.
When Should Healthcare Workers With Coronavirus Disease 2019 (COVID-19) Return to Work? An Analysis of Follow-up Antigen Test Results After a Positive COVID Test
Authors: Baffoe-Bonnie Anthony , Swann Mandy C , Kim Hyun Sue
Published: March 2023

A high percentage of healthcare workers (HCWs) who had met the Centers for Disease Control and Prevention criteria for returning to work 5 days after symptom onset remained positive for their return-to-work COVID-19 antigen test, suggesting continued infectiousness. Boosted HCWs were more likely to be antigen positive on their return-to-work test compared to unvaccinated HCWs, which merits further research.
Necrotizing Soft Tissue Infections in South Australia: A 15-Year Review
Authors: Tam Patrick Chung Kay , Kennedy Brendan , Ashokan Anushia
Published: March 2023

Necrotizing soft tissue infections (NSTIs) are associated with high morbidity and mortality. We retrospectively examined the impact of empiric antimicrobials coupled with early surgery on mortality in NSTI. Early surgery independently reduced 30-day mortality (odds ratio, .16; 95% confidence interval, .05–.51; P < .001) that was not further augmented by empiric antimicrobial choice.
Multiwavelength studies of G298.6−0.0: An old GeV supernova remnant interacting with molecular clouds
Authors: Yeung Paul K H , Bamba Aya , Sano Hidetoshi
Published: March 2023

Hadronic γ-ray sources associated with supernova remnants (SNRs) can serve as stopwatches for the escape of cosmic rays from SNRs, which gradually develops from highest-energy particles to lowest-energy particles with time. In this work, we analyze the 13.7 yr Fermi-LAT data to investigate the γ-ray feature in/around the SNR G298.6−0.0 region. With γ-ray spatial analyses, we detect three point-like components. Among them, Src-NE is at the eastern SNR shell, and Src-NW is adjacent to the western edge of this SNR. Src-NE and Src-NW demonstrate spectral breaks at energies around/below 1.8 GeV, suggesting an old SNR age of >10 kyr. We also look into the X-ray emission from the G298.6−0.0 region, with the Chandra-ACIS data. We detected an extended keV source having a centrally filled structure inside the radio shell. The X-ray spectra are well fitted by a model which assumes a collisional ionization equilibrium of the thermal plasma, further supporting an old SNR age. Based on our analyses of the NANTEN CO- and ATCA-Parkes H i-line data, we determined a kinematic distance of ∼10.1 kpc from us to G298.6−0.0. This distance entails a large physical radius of the SNR of ∼15.5 pc, which is additional evidence for an old age of >10 kyr. Besides this, the CO data cube enables us to three-dimensionally locate the molecular clouds (MCs) which are potentially interacting with SNR G298.6−0.0 and could account for the hadronic γ-rays detected at Src-NE or Src-NW. Furthermore, the multiwavelength observational properties unanimously imply that the SNR–MC interaction occurs mainly in the north-eastern direction.
FAR-RED INSENSITIVE 219 and phytochrome B corepress shade avoidance via modulating nuclear speckle formation
Authors: Peng Kai-Chun , Siao Wei , Hsieh Hsu-Liang
Published: March 2023

Plants can sense the shade from neighboring plants by detecting a reduction of the red:far-red light (R:FR) ratio. Phytochrome B (phyB) is the primary photoreceptor that perceives shade light and regulates jasmonic acid (JA) signaling. However, the molecular mechanisms underlying phyB and JA signaling integration in shade responses remain largely unknown. Here, we show the interaction of phyB and FAR-RED INSENSITIVE 219 (FIN219)/JASMONATE RESISTANT1 (JAR1) in a functional demand manner in Arabidopsis (Arabidopsis thaliana) seedling development. Genetic evidence and interaction studies indicated that phyB and FIN219 synergistically and negatively regulate shade-induced hypocotyl elongation. Moreover, phyB interacted with various isoforms of FIN219 under high and low R:FR light. Methyl jasmonate (MeJA) treatment, FIN219 mutation, and PHYBOE digalactosyldiacylglycerol synthase1-1 (dgd1-1) plants, which show increased levels of JA, altered the patterns of phyB-associated nuclear speckles under the same conditions. Surprisingly, PHYBOE dgd1-1 showed a shorter hypocotyl phenotype than its parental mutants under shade conditions. Microarray assays using PHYBOE and PHYBOE fin219-2 indicated that PHYB overexpression substantially affects defense response-related genes under shade light and coregulates expression of auxin-responsive genes with FIN219. Thus, our findings reveal that phyB substantially crosstalks with JA signaling through FIN219 to modulate seedling development under shade light.
Phylogenetic analyses of seven protein families refine the evolution of small RNA pathways in green plants
Authors: Bélanger Sébastien , Zhan Junpeng , Meyers Blake C
Published: March 2023

Several protein families participate in the biogenesis and function of small RNAs (sRNAs) in plants. Those with primary roles include Dicer-like (DCL), RNA-dependent RNA polymerase (RDR), and Argonaute (AGO) proteins. Protein families such as double-stranded RNA-binding (DRB), SERRATE (SE), and SUPPRESSION OF SILENCING 3 (SGS3) act as partners of DCL or RDR proteins. Here, we present curated annotations and phylogenetic analyses of seven sRNA pathway protein families performed on 196 species in the Viridiplantae (aka green plants) lineage. Our results suggest that the RDR3 proteins emerged earlier than RDR1/2/6. RDR6 is found in filamentous green algae and all land plants, suggesting that the evolution of RDR6 proteins coincides with the evolution of phased small interfering RNAs (siRNAs). We traced the origin of the 24-nt reproductive phased siRNA-associated DCL5 protein back to the American sweet flag (Acorus americanus), the earliest diverged, extant monocot species. Our analyses of AGOs identified multiple duplication events of AGO genes that were lost, retained, or further duplicated in subgroups, indicating that the evolution of AGOs is complex in monocots. The results also refine the evolution of several clades of AGO proteins, such as AGO4, AGO6, AGO17, and AGO18. Analyses of nuclear localization signal sequences and catalytic triads of AGO proteins shed light on the regulatory roles of diverse AGOs. Collectively, this work generates a curated and evolutionarily coherent annotation for gene families involved in plant sRNA biogenesis/function and provides insights into the evolution of major sRNA pathways.