bluuebunny/crossref_metadata_2025 huggingface dataset:
Linga’s Dream?
Authors: Janzen Philip
Published: September 2022

This article is about a young farmer named Linga and his encounter with a water spirit in Oubangui-Chari (present-day Central African Republic) in 1930. It is also about the telling and re-telling of Linga’s encounter as the story was transcribed into Banda, translated into French, and rewritten as an ethnographic folktale. Responsible for these transformations were two Banda interpreters and a colonial administrator from the Caribbean. In the last two decades, historians of colonialism have turned increasingly to interpreters and other intermediaries. Often missing from this scholarship, however, are analyses of the granular details—of how colonial intermediaries used transcription, translation, and other methods to create new words, texts, and ideas. Linguistic anthropologists refer to such interventions as “entextualization,” the process by which fragments of discourse are extracted from their immediate settings and rendered into detached texts. Drawing on this scholarship, I argue that tracing the granular processes of entextualization opens up new vantage points from which to study the role of colonial intermediaries in the production of knowledge. The article also illuminates a methodology for mapping otherwise invisible constellations of language, meaning, and colonial power.
Urdu Ethics Literature and the Diversity of Muslim Thought in Colonial India
Authors: Mir Farina
Published: September 2022

This essay discusses Urdu-language akhlaq (ethics) texts produced and circulated in late-colonial India (1858–1947), situating them both within a classical genre of Islamic ethics and in the context of Indian vernacular print culture. It focuses on three akhlaq texts published between the 1870s and 1930s to consider contemporary Muslim ethical concerns and schema, arguing that the genre points to a widespread, everyday, and unexceptional Muslim subjectivity that placed a high value on ethical striving. The essay offers new perspectives on the history of Muslims in late-colonial India by highlighting a non-institutional, diffuse, and capacious intellectual formation whose ideas were disseminated through print in a commercial market. It also expands existing notions of Muslim authority from individuals—such as the ulama (Muslim clerical class)—and institutions—such as madrasas (religious schools and seminaries)—to include literary genres themselves. Finally, the article broadens the range of Muslim subject-positions represented in scholarship on Islam in colonial India.
Improved NSGA-II algorithms for multi-objective biomarker discovery
Authors: Cattelani Luca , Fortino Vittorio
Published: September 2022

Motivation

In modern translational research, the development of biomarkers heavily relies on use of omics technologies, but implementations with basic data mining algorithms frequently lead to false positives. Non-dominated Sorting Genetic Algorithm II (NSGA2) is an extremely effective algorithm for biomarker discovery but has been rarely evaluated against large-scale datasets. The exploration of the feature search space is the key to NSGA2 success but in specific cases NSGA2 expresses a shallow exploration of the space of possible feature combinations, possibly leading to models with low predictive performances.

Results

We propose two improved NSGA2 algorithms for finding subsets of biomarkers exhibiting different trade-offs between accuracy and feature number. The performances are investigated on gene expression data of breast cancer patients. The results are compared with NSGA2 and LASSO. The benchmarking dataset includes internal and external validation sets. The results show that the proposed algorithms generate a better approximation of the optimal trade-offs between accuracy and set size. Moreover, validation and test accuracies are better than those provided by NSGA2 and LASSO. Remarkably, the GA-based methods provide biomarkers that achieve a very high prediction accuracy (>80%) with a small number of features (<10), representing a valid alternative to known biomarker models, such as Pam50 and MammaPrint.

Availability and implementation

The software is publicly available on GitHub at github.com/UEFBiomedicalInformaticsLab/BIODAI/tree/main/MOO.

Supplementary information

Supplementary data are available at Bioinformatics online.
CRISPRtracrRNA: robust approach for CRISPR tracrRNA detection
Authors: Mitrofanov Alexander , Ziemann Marcus , Alkhnbashi Omer S , Hess Wolfgang R , Backofen Rolf
Published: September 2022

Motivation

The CRISPR-Cas9 system is a Type II CRISPR system that has rapidly become the most versatile and widespread tool for genome engineering. It consists of two components, the Cas9 effector protein, and a single guide RNA that combines the spacer (for identifying the target) with the tracrRNA, a trans-activating small RNA required for both crRNA maturation and interference. While there are well-established methods for screening Cas effector proteins and CRISPR arrays, the detection of tracrRNA remains the bottleneck in detecting Class 2 CRISPR systems.

Results

We introduce a new pipeline CRISPRtracrRNA for screening and evaluation of tracrRNA candidates in genomes. This pipeline combines evidence from different components of the Cas9-sgRNA complex. The core is a newly developed structural model via covariance models from a sequence-structure alignment of experimentally validated tracrRNAs. As additional evidence, we determine the terminator signal (required for the tracrRNA transcription) and the RNA–RNA interaction between the CRISPR array repeat and the 5′-part of the tracrRNA. Repeats are detected via an ML-based approach (CRISPRidenify). Providing further evidence, we detect the cassette containing the Cas9 (Type II CRISPR systems) and Cas12 (Type V CRISPR systems) effector protein. Our tool is the first for detecting tracrRNA for Type V systems.

Availability and implementation

The implementation of the CRISPRtracrRNA is available on GitHub upon requesting the access permission, (https://github.com/BackofenLab/CRISPRtracrRNA). Data generated in this study can be obtained upon request to the corresponding person: Rolf Backofen (backofen@informatik.uni-freiburg.de).

Supplementary information

Supplementary data are available at Bioinformatics online.
DeepZF: improved DNA-binding prediction of C2H2-zinc-finger proteins by deep transfer learning
Authors: Aizenshtein-Gazit Sofia , Orenstein Yaron
Published: September 2022

Motivation

Cys2His2 zinc-finger (C2H2-ZF) proteins are the largest class of human transcription factors and hence play central roles in gene regulation and cell function. C2H2-ZF proteins are characterized by a DNA-binding domain containing multiple ZFs. A subset of the ZFs bind diverse DNA triplets. Despite their central roles, little is known about which of their ZFs are binding and how the DNA-binding preferences are encoded in the amino acid sequence of each ZF.

Results

We present DeepZF, a deep-learning-based pipeline for predicting binding ZFs and their DNA-binding preferences given only the amino acid sequence of a C2H2-ZF protein. To the best of our knowledge, we compiled the first in vivo dataset of binding and non-binding ZFs for training the first ZF-binding classifier. Our classifier, which is based on a novel protein transformer, achieved an average AUROC of 0.71. Moreover, we took advantage of both in vivo and in vitro datasets to learn the recognition code of ZF-DNA binding through transfer learning. Our newly developed model, which is the first to utilize deep learning for the task, achieved an average Pearson correlation greater than 0.94 over each of the three DNA binding positions. Together, DeepZF outperformed extant methods in the task of C2H2-ZF protein DNA-binding preferences prediction: it achieved an average Pearson correlation of 0.42 in motif similarity compared with an average correlation smaller than 0.1 achieved by extant methods. By applying established interpretability techniques, we show that DeepZF inferred biologically relevant binding principles, such as the effect of amino acid residue positions on ZF DNA-binding potential.

Availability and implementation

DeepZF code, model, and results are available via github.com/OrensteinLab/DeepZF.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cross-modality and self-supervised protein embedding for compound–protein affinity and contact prediction
Authors: You Yuning , Shen Yang
Published: September 2022

Motivation

Computational methods for compound–protein affinity and contact (CPAC) prediction aim at facilitating rational drug discovery by simultaneous prediction of the strength and the pattern of compound–protein interactions. Although the desired outputs are highly structure-dependent, the lack of protein structures often makes structure-free methods rely on protein sequence inputs alone. The scarcity of compound–protein pairs with affinity and contact labels further limits the accuracy and the generalizability of CPAC models.

Results

To overcome the aforementioned challenges of structure naivety and labeled-data scarcity, we introduce cross-modality and self-supervised learning, respectively, for structure-aware and task-relevant protein embedding. Specifically, protein data are available in both modalities of 1D amino-acid sequences and predicted 2D contact maps that are separately embedded with recurrent and graph neural networks, respectively, as well as jointly embedded with two cross-modality schemes. Furthermore, both protein modalities are pre-trained under various self-supervised learning strategies, by leveraging massive amount of unlabeled protein data. Our results indicate that individual protein modalities differ in their strengths of predicting affinities or contacts. Proper cross-modality protein embedding combined with self-supervised learning improves model generalizability when predicting both affinities and contacts for unseen proteins.

Availability and implementation

Data and source codes are available at https://github.com/Shen-Lab/CPAC.

Supplementary information

Supplementary data are available at Bioinformatics online.
Linking cells across single-cell modalities by synergistic matching of neighborhood structure
Authors: Hristov Borislav H , Bilmes Jeffrey A , Noble William Stafford
Published: September 2022

Motivation

A wide variety of experimental methods are available to characterize different properties of single cells in a complex biosample. However, because these measurement techniques are typically destructive, researchers are often presented with complementary measurements from disjoint subsets of cells, providing a fragmented view of the cell’s biological processes. This creates a need for computational tools capable of integrating disjoint multi-omics data. Because different measurements typically do not share any features, the problem requires the integration to be done in unsupervised fashion. Recently, several methods have been proposed that project the cell measurements into a common latent space and attempt to align the corresponding low-dimensional manifolds.

Results

In this study, we present an approach, Synmatch, which produces a direct matching of the cells between modalities by exploiting information about neighborhood structure in each modality. Synmatch relies on the intuition that cells which are close in one measurement space should be close in the other as well. This allows us to formulate the matching problem as a constrained supermodular optimization problem over neighborhood structures that can be solved efficiently. We show that our approach successfully matches cells in small real multi-omics datasets and performs favorably when compared with recently published state-of-the-art methods. Further, we demonstrate that Synmatch is capable of scaling to large datasets of thousands of cells.

Availability and implementation

The Synmatch code and data used in this manuscript are available at https://github.com/Noble-Lab/synmatch.
Insights into performance evaluation of compound–protein interaction prediction methods
Authors: Yaseen Adiba , Amin Imran , Akhter Naeem , Ben-Hur Asa , Minhas Fayyaz
Published: September 2022

Motivation

Machine-learning-based prediction of compound–protein interactions (CPIs) is important for drug design, screening and repurposing. Despite numerous recent publication with increasing methodological sophistication claiming consistent improvements in predictive accuracy, we have observed a number of fundamental issues in experiment design that produce overoptimistic estimates of model performance.

Results

We systematically analyze the impact of several factors affecting generalization performance of CPI predictors that are overlooked in existing work: (i) similarity between training and test examples in cross-validation; (ii) synthesizing negative examples in absence of experimentally verified negative examples and (iii) alignment of evaluation protocol and performance metrics with real-world use of CPI predictors in screening large compound libraries. Using both state-of-the-art approaches by other researchers as well as a simple kernel-based baseline, we have found that effective assessment of generalization performance of CPI predictors requires careful control over similarity between training and test examples. We show that, under stringent performance assessment protocols, a simple kernel-based approach can exceed the predictive performance of existing state-of-the-art methods. We also show that random pairing for generating synthetic negative examples for training and performance evaluation results in models with better generalization in comparison to more sophisticated strategies used in existing studies. Our analyses indicate that using proposed experiment design strategies can offer significant improvements for CPI prediction leading to effective target compound screening for drug repurposing and discovery of putative chemical ligands of SARS-CoV-2-Spike and Human-ACE2 proteins.

Availability and implementation

Code and supplementary material available at https://github.com/adibayaseen/HKRCPI.

Supplementary information

Supplementary data are available at Bioinformatics online.
Highly significant improvement of protein sequence alignments with AlphaFold2
Authors: Baltzis Athanasios , Mansouri Leila , Jin Suzanne , Langer Björn E , Erb Ionas , Notredame Cedric
Published: September 2022

Motivation

Protein sequence alignments are essential to structural, evolutionary and functional analysis, but their accuracy is often limited by sequence similarity unless molecular structures are available. Protein structures predicted at experimental grade accuracy, as achieved by AlphaFold2, could therefore have a major impact on sequence analysis.

Results

Here, we find that multiple sequence alignments estimated on AlphaFold2 predictions are almost as accurate as alignments estimated on experimental structures and significantly closer to the structural reference than sequence-based alignments. We also show that AlphaFold2 structural models of relatively low quality can be used to obtain highly accurate alignments. These results suggest that, besides structure modeling, AlphaFold2 encodes higher-order dependencies that can be exploited for sequence analysis.

Availability and implementation

All data, analyses and results are available on Zenodo (https://doi.org/10.5281/zenodo.7031286). The code and scripts have been deposited in GitHub (https://github.com/cbcrg/msa-af2-nf) and the various containers in (https://cloud.sylabs.io/library/athbaltzis/af2/alphafold, https://hub.docker.com/r/athbaltzis/pred).

Supplementary information

Supplementary data are available at Bioinformatics online.
Comparative Effectiveness of BNT162b2 and mRNA-1273 Booster Dose After BNT162b2 Primary Vaccination Against the Omicron Variants: A Retrospective Cohort Study Using Large-Scale Population-Based Registries in Japan
Authors: Ono Sachiko , Michihata Nobuaki , Yamana Hayato , Uemura Kohei , Ono Yosuke , Jo Taisuke , Yasunaga Hideo
Published: September 2022

Background

Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown.

Methods

We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and coronavirus disease 2019 (COVID-19) infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between 22 November 2021, and 15 April 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16–44, 45–64, 65–84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses.

Results

During the study period, we identified 62 586 (40.4%), 51 490 (33.2%), and 40 849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories.

Conclusions

Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs.
Cryptanalysis on Reduced-Round 3D and Saturnin
Authors: Zhang Li , Wu Wenling , Zheng YaFei , Wang Bolin
Published: September 2022

3D is an Advanced Encryption Standard (AES)-like cipher employed 3D structure proposed in 2008. The main innovation of 3D is the multi-dimensional state, generalizing the design of Rijndael and allowing block sizes beyond the 256-bit boundary. Saturnin, a lightweight block cipher has been selected as a second-round candidate in the National Institute of Standards and Technology standardization for lightweight cryptography. It also employs a 3D structure and provides high security against quantum and classic attacks. The exchange-equivalence attacks proposed by Bardeh and Rønjom consider how quadruples of plaintexts confirm distinguishable properties for AES. It is similar to the principle of yoyo attack, but it can find a longer number of rounds of distinguisher. In this paper, we investigate the exchange-equivalence attack on 3D and yoyo attack on Saturnin. Our new results turn out to be the first secret-key chosen plaintext distinguisher for 10-round 3D. The complexity of the distinguisher is about $2^{364.2}$ in terms of data, memory and computational complexity. For Saturnin, we propose the first six-super-round impossible differential yoyo attack, which is suitable for the two-S-layer version. Compared with the previous impossible differential attacks in the design report of Saturnin, the attacks presented here are the best in terms of the complexity under the chosen-plaintext scenario.
The Incidence and Prevalence of Paediatric- and Adult-Onset Inflammatory Bowel Disease in Denmark During a 37-Year Period: A Nationwide Cohort Study (1980–2017)
Authors: Dorn-Rasmussen Maria , Lo Bobby , Zhao Mirabella , Kaplan Gilaad G , Malham Mikkel , Wewer Vibeke , Burisch Johan
Published: September 2022

Background

Incidence rates of inflammatory bowel disease [IBD] reported from developed countries are rising, with some levelling out. The aim of this study was to assess the disease burden of IBD by estimating the incidence and prevalence across age groups and projecting these to 2030 in a high-incidence country.

Methods

Using an algorithm [incorporating ICD codes, medications and histopathology], patients [n = 69 862] diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC] between 1980 and 2017 were identified in the Danish National Patient Registry and included in a nationwide cohort.

Results

From 1980 to 2017 the overall incidence of CD increased from 5.1 [95% CI: 4.5–5.8] to 15.6 [95% CI: 14.6–16.6] per 100 000, while the incidence of UC increased from 6.2 [95% CI: 5.5–6.9] to 27.2 [95% CI: 25.9–28.6] per 100 000. For paediatric-onset CD [pCD], the incidence increased from 1.9 [95% CI: 1.2–2.8] to 9.9 [95% CI: 8.1–11.8] per 100 000 and from 1.8 [95% CI: 1.2–2.8] to 8.7 [95% CI: 7.1– 10.5] per 100 000 for paediatric-onset UC [pUC]. In 2017, the prevalence of CD and UC was 293 [95% CI: 288–297] and 523 [95% CI: 517–528] per 100 000. For pCD and pUC, the prevalence was 35 [95% CI: 31–38] and 28 [95% CI: 26–32] per 100 000.

Conclusions

The incidence of paediatric- and adult-onset IBD in Denmark continues to increase and is among the highest in the world.
Epidemiology, Treatment Strategy, Natural Disease Course and Surgical Outcomes of Patients with Ulcerative Colitis in Western Hungary – A Population-based Study Between 2007 and 2018: Data from the Veszprem County Cohort
Authors: Kurti Zsuzsanna , Gonczi Lorant , Lakatos Laszlo , Golovics Petra A , Pandur Tunde , David Gyula , Erdelyi Zsuzsanna , Szita Istvan , Lakatos Peter L
Published: September 2022

Background and Aims

The number of population-based studies in ulcerative colitis [UC] from Eastern Europe is limited. Our aim here was to analyse the incidence, prevalence, disease phenotype, treatment strategy, disease course and colectomy rates in a prospective population-based inception cohort including UC patients diagnosed between 2007 and 2018. The present study is a continuation of the Veszprem IBD cohort since 1977.

Methods

In total, 467 UC patients were included [male/female: 236/231; median age at diagnosis: 36 years, IQR: 25–54 years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. The mean length of follow-up was 8.34 ± 3.6 years. Demographic data were derived from the Hungarian Central Statistical Office.

Results

The mean incidence rate was 11.02/105 person-years in this 12-year period. Prevalence was 317.79/105 persons in 2015. Disease extent at diagnosis was proctitis [E1] in 22.3%, left-sided colitis [E2] in 43.9% and extensive colitis [E3] in 33.8%. The probability of disease extent progression was 11.6% [SE: 1.8] after 5 years. The distribution of maximal therapeutic steps was 5-ASA in 46.9%, corticosteroids in 16.3%, immunosuppressives in 19.3% and biologicals in 16.5%. The probability of receiving biological therapy after diagnosis was 9.9% [SE: 1.4] at 3 years. The overall colectomy rate was 4.1% in the population. The probability of colectomy was 1.5% [SE: 0.6] at 1 year, 3.6% [SE: 0.9] at 5 years and 4.4% [SE: 1.0] at 10 years.

Conclusions

The incidence of UC was high in Hungary, similar to high-incidence areas in Western Europe. Treatment strategies are in line with the biological era. The probability of progressing to proximal disease, and the medium- and long-term colectomy rates were both lower compared with data from Western European centres.
Addressing Health Inequities in Digital Clinical Trials: A Review of Challenges and Solutions From the Field of HIV Research
Authors: Wirtz Andrea L , Logie Carmen H , Mbuagbaw Lawrence
Published: September 2022

Clinical trials are considered the gold standard for establishing efficacy of health interventions, thus determining which interventions are brought to scale in health care and public health programs. Digital clinical trials, broadly defined as trials that have partial to full integration of technology across implementation, interventions, and/or data collection, are valued for increased efficiencies as well as testing of digitally delivered interventions. Although recent reviews have described the advantages and disadvantages of and provided recommendations for improving scientific rigor in the conduct of digital clinical trials, few to none have investigated how digital clinical trials address the digital divide, whether they are equitably accessible, and if trial outcomes are potentially beneficial only to those with optimal and consistent access to technology. Human immunodeficiency virus (HIV), among other health conditions, disproportionately affects socially and economically marginalized populations, raising questions of whether interventions found to be efficacious in digital clinical trials and subsequently brought to scale will sufficiently and consistently reach and provide benefit to these populations. We reviewed examples from HIV research from across geographic settings to describe how digital clinical trials can either reproduce or mitigate health inequities via the design and implementation of the digital clinical trials and, ultimately, the programs that result. We discuss how digital clinical trials can be intentionally designed to prevent inequities, monitor ongoing access and utilization, and assess for differential impacts among subgroups with diverse technology access and use. These findings can be generalized to many other health fields and are practical considerations for donors, investigators, reviewers, and ethics committees engaged in digital clinical trials.
The future of individualized cardiovascular care: how wearables could be integrated to improve outcomes
Authors: Hung John D , Brugaletta Salvatore , Spratt James C
Published: September 2022

Personalized medicine is a concept all clinicians must strive to deliver. Recent advances in technology increasingly offer new opportunities to personalize care, not least in cardiovascular medicine. Health trackers and wearables are technologies in an explosive phase of development. They allow accurate and continuous measurement of bio-data, recorded and analysed using apps and mobile devices. However, although there is huge potential, most physicians and healthcare organizations are yet to realize the value of integrating wearables into routine clinical practice. We discuss how this state-of-the-art technology can support patients in making meaningful lifestyle changes and revolutionize the future of cardiovascular medicine.
Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model
Authors: van Weperen Valerie Y H , ter Horst Iris , Dunnink Albert , Bossu Alexandre , Salden Odette A , Beekman Henriette D M , Oros Avram , Bourgonje Vincent , Stams Thom , Meine Mathias , Vos Marc A
Published: September 2022

Aims

Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA.

Methods and results

Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10]. After ≥3 weeks of bradycardic remodelling, Torsade de Pointes arrhythmia (TdP) inducibility, defined as ≥3 TdP/10 min, was tested with specific IKr-blocker dofetilide (25 μg/kg/5 min). Mechanical dyssynchrony was assessed by echocardiography as time-to-peak (TTP) of left ventricular (LV) free-wall minus septum (ΔTTP). Electrical intraventricular dyssynchrony was assessed as slope of regression line correlating intraventricular LV activation time (AT) and activation recovery interval (ARI). Under sinus rhythm, contraction occurred synchronous (ΔTTP: −8.6 ± 28.9 ms), and latest activated regions seemingly had slightly longer repolarization (AT–ARI slope: −0.4). Acute AV block increased MD in all groups, but following ≥3 weeks of remodelling IVR animals became significantly more TdP inducible (19/29 IVR vs. 5/12 RVA and 2/10 CRT, both P < 0.05 vs. IVR). After chronic AVA, intraventricular MD was lowest in CRT animals (ΔTTP: −8.5 ± 31.2 vs. 55.80 ± 20.0 and 82.7 ± 106.2 ms in CRT, IVR, and RVA, respectively, P < 0.05 RVA vs. CRT). Although dofetilide steepened negative AT–ARI slope in all groups, this heterogeneity in dofetilide-induced ARI prolongation seemed least pronounced in CRT animals (slope to −0.8, −3.2 and −4.5 in CRT, IVR and RVA, respectively).

Conclusion

Severity of intraventricular MD affects the extent of electrical remodelling and pro-arrhythmic outcome in the CAVB dog model.
Rapid large-scale genomic introgression in Arabidopsis suecica via an autoallohexaploid bridge
Authors: Oruganti Vidya , Toegelová Helena , Pečinka Aleš , Madlung Andreas , Schneeberger Korbinian
Published: September 2022

Gene flow between species in the genus Arabidopsis occurs in significant amounts, but how exactly gene flow is achieved is not well understood. Polyploidization may be one avenue to explain gene flow between species. One problem, however, with polyploidization as a satisfying explanation is the occurrence of lethal genomic instabilities in neopolyploids as a result of genomic exchange, erratic meiotic behavior, and genomic shock. We have created an autoallohexaploid by pollinating naturally co-occurring diploid Arabidopsis thaliana with allotetraploid Arabidopsis suecica (an allotetraploid composed of A. thaliana and Arabidopsis arenosa). Its triploid offspring underwent spontaneous genome duplication and was used to generate a multigenerational pedigree. Using genome resequencing, we show that 2 major mechanisms promote stable genomic exchange in this population. Legitimate meiotic recombination and chromosome segregation between the autopolyploid chromosomes of the 2 A. thaliana genomes occur without any obvious bias for the parental origin and combine the A. thaliana haplotypes from the A. thaliana parent with the A. thaliana haplotypes from A. suecica similar to purely autopolyploid plants. In addition, we repeatedly observed that occasional exchanges between regions of the homoeologous chromosomes are tolerated. The combination of these mechanisms may result in gene flow leading to stable introgression in natural populations. Unlike the previously reported resynthesized neoallotetraploid A. suecica, this population of autoallohexaploids contains mostly vigorous, and genetically, cytotypically, and phenotypically variable individuals. We propose that naturally formed autoallohexaploid populations might serve as an intermediate bridge between diploid and polyploid species, which can facilitate gene flow rapidly and efficiently.
Chromosome-level genome assembly of Amomum tsao-ko provides insights into the biosynthesis of flavor compounds
Authors: Li Ping , Bai Genxiang , He Jiangbin , Liu Bo , Long Junru , Morcol Taylan , Peng Weiyao , Quan Fan , Luan Xinbo , Wang Zhenzhen , Zhao Yi , Cha Yunsheng , Liu Yuanyuan , He Juncai , Wu Lianzhang , Yang Yi , Kennelly Edward J , Yang Quan , Sun Lirong , Chen Zepeng , Qian Wanqiang , Hu Jian , Yan Jian
Published: September 2022

Amomum tsao-ko is an economically important spice plant in the ginger family (Zingiberaceae). The dried ripe fruit has been widely used as spice and medicine in Southeast Asia due to its distinct flavor metabolites. However, there is little genomic information available to understand the biosynthesis of its characteristic flavor compounds. Here, we present a high-quality chromosome-level genome of A. tsao-ko with a total length of 2.08 Gb assembled into 24 chromosomes. Potential relationships between genetic variation and chemical constituents were analyzed by a genome-wide association study of 119 representative A. tsao-ko specimens in China. Metabolome and transcriptome correlation analysis of different plant organs and fruit developmental stages revealed the proposed biosynthesis of the characteristic bicyclononane aldehydes and aromatic metabolites in A. tsao-ko fruit. Transcription factors of 20 families may be involved in the regulatory network of terpenoids. This study provides genomic and chemical insights into the biosynthesis of characteristic aroma and flavor constituents, which can be used to improve the quality of A. tsao-ko as food and medicine.
A scoping review of patient safety research carried out in Saudi Arabian hospitals
Authors: Kaud Yazeed , O’Connor Paul , O’Malley Roisin , Dunne Rosie , Lydon Sinéad
Published: September 2022

Background

In Saudi Arabia, there has been substantial investment in patient safety initiatives.

Objectives

The objectives of this scoping review were to map the quantity and nature of existing research on patient safety in Saudi Arabian hospitals and to identify gaps in the extant literature.

Methods

Electronic searches were completed using five databases. Peer-reviewed studies written in English or Arabic that focused on patient safety in hospitals in Saudi Arabia were reviewed. Studies concerned with measuring and monitoring safety were categorised using the Measuring and Monitoring Safety Framework. The hierarchy of intervention effectiveness was used to categorise interventions studies.

Results

A total of 2489 studies were screened, with 67 meeting the inclusion criteria. In total, 61 (91%) of included studies were focused on the measurement or monitoring of safety. Six studies (9%) considered interventions to improve patient safety. Of these, 31.3% of the studies assessed past harm, 1.5% reliability of safety systems, 7.5% sensitivity to operations, 47.8% anticipation and preparedness, and 3% integration and learning. Of the six intervention studies, one study reported enforcing functions interventions, one simplification and standardisation, two rules and policies, and two studies applied an education and training intervention.

Conclusion

As is the case internationally, there is a paucity of evidence on interventions to improve safety in Saudi Arabia. This review has identified areas of strength, redundancy, and gaps in patient safety research in the Saudi Arabia. However, the findings also have implications for the MMS in other healthcare systems.
A novel noninvasive genetic survey technique for small mammals
Authors: Aylward Cody M , Grahn Robert A , Barthman-Thompson Laureen M , Kelt Douglas A , Sacks Benjamin N , Statham Mark J
Published: September 2022

Noninvasive genetic surveys, often conducted by collecting fecal samples, have become a popular tool for surveying wildlife, but have primarily been applied to species with large and conspicuous scat. Although many small mammals are threatened, endangered, or data deficient, noninvasive genetic surveys have rarely been applied due to the challenges of detecting their inconspicuous fecal pellets. As part of a broader study of the endangered salt marsh harvest mouse (Reithrodontomys raviventris), we developed a noninvasive genetic survey technique for the community of small mammals in their putative range. We designed bait stations to passively collect fecal samples from rodents, and developed a multiplex primer set that amplified unique fragment sizes for salt marsh harvest mice and four other sympatric species. We tested the primer set on positive controls and on fecal pellets collected from bait stations at two regularly monitored field sites known to have very different densities of salt marsh harvest mice. The multiplex amplified DNA from all five species, even when all five species were present in a single sample. A positive species identification was made for all field-collected samples, and 43% of these field-collected samples had multispecies detections. The combination of bait stations and genetic species identification proved to be an effective means of noninvasively surveying small mammals in potential salt marsh harvest mouse habitat. The sampling technique should be applicable to a wide variety of small mammals in other systems.
Tropical and Temperate Lineages of Rhipicephalus sanguineus s.l. Ticks (Acari: Ixodidae) Host Different Strains of Coxiella-like Endosymbionts
Authors: Brophy Maureen , Walker Kathleen R , Adamson Johnathan E , Ravenscraft Alison
Published: September 2022

Nonpathogenic bacteria likely play important roles in the biology and vector competence of ticks and other arthropods. Coxiella, a gram-negative gammaproteobacterium, is one of the most commonly reported maternally inherited endosymbionts in ticks and has been associated with over 40 tick species. Species-specific Coxiella-like endosymbionts (CLEs) have been reported in the brown dog tick, Rhipicephalus sanguineus sensu lato (Acari: Ixodidae), throughout the world, while recent research suggests low Coxiella diversity among tick species. We investigated CLE diversity among R. sanguineus s.l. ticks across Arizona. We detected 37 recurrent sequence variants (SVs) of the symbiont, indicating greater diversity in these symbiotic bacteria than previously reported. However, two SVs accounted for the vast majority of 16S rRNA amplicon reads. These two dominant CLEs were both closely related to Candidatus C. mudrowiae, an identified symbiont of Rhipicephalus turanicus ticks. One strain strongly associated with the tropical lineage of R. sanguineus s.l. while the other was found almost exclusively in the temperate lineage, supporting the conclusion that CLEs are primarily vertically transmitted. However, occasional mismatches between tick lineage and symbiont SV indicate that horizontal symbiont transfer may occur, perhaps via cofeeding of ticks from different lineages on the same dog. This study advances our understanding of CLE diversity in Rh. sanguineus s.l.
P041 Preliminary evaluation of gradient concentration strips for detection of terbinafine resistance in Trichophyton spp.
Authors: Bidaud Anne-Laure , Moreno-Sabater Alicia , Normand Anne-Cécile , Cremer Geneviève , Foulet Françoise , Brun Sophie , Ayachi Aymen , Imbert Sébastien , Chowdhary Anuradha , Dannaoui Eric
Published: September 2022

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

 

Objectives

Dermatophytosis is the most common superficial fungal infection. Trichophyton rubrum and T. mentagrophytes are the most frequently isolated species, but their incidence varies according to geographical regions. Terbinafine is the main molecule used to treat this type of infection. In recent years, a high incidence of chronic infections, reinfections, and treatment failures due to a newly described specie, T. indotineae, have been reported in India and recently described in Europe. It is currently a public health problem for the management of these infections in this country.

Until now, the monitoring of dermatophyte susceptibility to antifungals was rarely performed due to the lack of standardized in vitro tests. Since then, an in vitro technique has been standardized by the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test terbinafine and other antifungals. Recently, a gradient concentration strip method has been marketed.

The aim of this study was to compare terbinafine susceptibility testing by the gradient concentration strip (GCS) method and the EUCAST standardized method.

Methods

A panel of 47 molecularly identified isolates of T. interdigitale, T. mentagrophytes, and T. indotineae was used. The panel included 39 terbinafine- susceptible isolates and 8 terbinafine resistant isolates for which the squalene epoxidase gene was sequenced.

Minimum inhibitory concentration (MIC) of terbinafine was determined using EUCAST microdilution broth method for dermatophytes. Inoculum was supplemented with cycloheximide and chloramphenicol. Final drug concentrations ranged from 0.008 to 8 μg/ml and microtiter plates were incubated at 25°C for 5 days. The MIC was determined spectrophotometrically with a 90% growth inhibition endpoint.

MIC of terbinafine was also determined using GCS (Terbinafine Ezy MIC™ Strip, HiMedia, India) on RPMI agar. The plates were incubated for 5 days at 25°C. After incubation, MIC was read by using a complete inhibition endpoint. Isolates were considered wild-type when MIC was ≤ 0.125 μg/ml.

Results

EUCAST MIC values ranged from 0.008 to 0.0625 μg/mL and from 0.25 to 16 μg/ml for susceptible and resistant isolates, respectively.

GCS MIC values ranged from 0.002 to 0.03 μg/ml and 0.125 to >32 for susceptible and resistant isolates, respectively.

The categorical agreement (percentage of strains found in the same category) by the two techniques was 98%.

Conclusion

These preliminary results show that GCS can detect resistance to terbinafine and could be used as a screening method. These results must be confirmed on a larger panel of isolates.
P142 Lodderomyces elongisporus: A n emerging cause of fung emia
Authors: Kaur Harsimran , Gupta Parakriti , Shankarnarayan Shamanth , Pandey Abhishek , Ghosh Anup , Chakrabarti Arunaloke , Rudramurthy Shivaprakash
Published: September 2022

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM

 

Background

Lodderomyces elongisporus, earlier considered as a sexual state of Candida parapsilosis, was described as a distinct species based on ribosomal RNA gene sequencing. Few cases of human infections by this yeast have been described from Mexico, China, Malaysia, Kuwait, Australia, and the USA. We describe here eight cases of fungemia by L. elongisporus from a tertiary care hospital in North India.

Methods

Clinical characteristics and risk factors associated with L. elongisporus fungaemia were evaluated. Yeast isolated from blood culture (BD BACTEC™ 9240, New Jersey, USA) was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS, Bruker Daltonik GmbH, Bremen, Germany) and sequencing of D1/D2 region of a large subunit of ribosomal DNA. We performed antifungal susceptibility testing for amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and micafungin by the microbroth dilution method recommended by the Clinical and Laboratory Standards Institute (CLSI).

Results

We report eight cases of fungemia caused by L. elongisporus at our tertiary care center. Of these, three were infants (males) and five were adults (3 males and 2 females). The mean age of adults was 43.4 years. Among the pediatric cases, underlying diseases included congenital heart disease/atrophic kidney (neonate), tracheoesophageal fistula (4 months), and late-onset neonatal sepsis (LONS). Among the adults, underlying illnesses included acute kidney injury (n = 2), superior mesenteric artery thrombosis with bowel gangrene (n = 1), diabetes (n = 1), and central nervous system (CNS) lymphoma (n = 1). The iatrogenic factors included the history of surgery (n = 3), admission to ICU (n = 3), presence of urinary catheter (n = 4), and presence of central venous catheter (n = 1). Seven patients were on broad-spectrum antibiotics. The mean stay in the hospital was 20.38 days. Three of the patients were managed with fluconazole. Six patients improved while one left against medical advice (LAMA) and one expired. The range of minimum inhibitory concentration (MIC) of all the isolates against antifungals was as follows: amphotericin B (0.03-0.25 μg/ml), fluconazole (0.125 μg/ml), voriconazole (0.03 μg/ml), itraconazole (0.03-0.06 μg/ml), posaconazole (0.03-0.25 μg/ml), caspofungin (0.03-0.06 μg/ml), micafungin (0.03-0.06 μg/ml), and anidulafungin (0.03 μg/ml).

Conclusion

Lodderomyces elongisporus is an emerging pathogenic yeast causing fungemia in patients with comorbidities and undergoing surgery or invasive interventions. Though no antifungal breakpoints exist for this yeast, all the isolates exhibited low MICs to all the tested antifungals.
S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire?
Authors: Carolus Hans , Sofras Dimitrios , Sephton-Clark Poppy , Goossens Louise , Chen Alicia , Pierson Siebe , Romero Celia Lobo , Subotić Ana , Meis Jacques F. , Cuomo Christina A. , Van Dijck Patrick
Published: September 2022

S2.5 Rare yeasts, September 21, 2022, 3:00 PM - 4:30 PM

Candida auris (C. auris) is a recently emerged human fungal pathogen of growing concern due to its ability to acquire extensive multidrug resistance (MDR) to all four antifungal drug classes. The unprecedented extent of MDR in C. auris, suggests accelerated resistance evolution, novel mechanisms of resistance, and/or potential fitness compensation. Despite being the first fungus to be officially considered an urgent antimicrobial resistance threat by the CDC (US), insights into the resistance mechanisms and evolutionary dynamics of C. auris are still scarce.

 

By using high-throughput in vitro experimental evolution with various antifungal drugs, we have obtained a library of resistant strains from four different clades. Through both genome and targeted sequencing, we have discovered novel mutations, especially for polyene resistance, which indicate new mechanisms of resistance and fitness compensation. For the validation of mutations, we have optimized a recyclable CRISPR/Cas9 tool for C. auris based on the C. albicans HIS-FLP system.

 

By mapping drug susceptibility responses of evolved strains across a library of several antifungals and repurposed drugs, we have discovered trends of cross-resistance and collateral sensitivity. Both phenomena have been extensively studied in tumors and bacteria but remain unexplored in fungi. In the light of these observations, we explore novel treatment schemes that prevent antifungal drug resistance development in C. auris and other pathogenic fungi.
Real-time detection of anomalies in large-scale transient surveys
Authors: Muthukrishna Daniel , Mandel Kaisey S , Lochner Michelle , Webb Sara , Narayan Gautham
Published: September 2022

New time-domain surveys, such as the Vera C. Rubin Observatory Legacy Survey of Space and Time, will observe millions of transient alerts each night, making standard approaches of visually identifying new and interesting transients infeasible. We present two novel methods of automatically detecting anomalous transient light curves in real-time. Both methods are based on the simple idea that if the light curves from a known population of transients can be accurately modelled, any deviations from model predictions are likely anomalies. The first modelling approach is a probabilistic neural network built using Temporal Convolutional Networks (TCNs) and the second is an interpretable Bayesian parametric model of a transient. We demonstrate our methods’ ability to provide anomaly scores as a function of time on light curves from the Zwicky Transient Facility. We show that the flexibility of neural networks, the attribute that makes them such a powerful tool for many regression tasks, is what makes them less suitable for anomaly detection when compared with our parametric model. The parametric model is able to identify anomalies with respect to common supernova classes with high precision and recall scores, achieving area under the precision-recall curves above 0.79 for most rare classes such as kilonovae, tidal disruption events, intermediate luminosity transients, and pair-instability supernovae. Our ability to identify anomalies improves over the lifetime of the light curves. Our framework, used in conjunction with transient classifiers, will enable fast and prioritized followup of unusual transients from new large-scale surveys.