bluuebunny/crossref_metadata_2025_split huggingface dataset:
A methodology for selection and quality control of the radiological computer vision deployment at the megalopolis scale
Authors: Andreychenko Anna E. , Logunova Tatiana A. , Gombolevskiy Victor A. , Nikolaev Aleksandr E. , Vladzymyrskyy Anton V. , Sinitsyn Valentin E. , Morozov Sergey P. 
Published: February 2022

AbstractIn recent years, there has been tremendous interest in the use of artificial intelligence (AI) in radiology in order to automate the interpretation. However, uncontrolled and widespread use of AI solutions may have negative consequences. Therefore, before implementing such technologies in healthcare, thorough training of personnel, adaptation of information systems, and standardized datasets for an external validation are required. All this necessitates a formation of a unique unified methodology. The best practices of AI introduction in diagnostic radiology are still subject to debate and require new results of a scientific-practical research with the assessment of implementation conditions.This work discusses expected issues and potential solutions for the introduction of computer vision-based technologies for automatic analysis of radiological examinations with an emphasis on the real-life experience gained during simultaneous AI implementation into practice of more than a hundred state radiology departments in 2020-2021 in Moscow, Russia (an experiment). The experiment used end-user software testing approaches, quality assurance of AI-based radiological solutions, and accuracy assessment of the AI-empowered diagnostic tools on local data. The methods were adapted and optimized to ensure a successful real-life radiological AI deployment on the extraordinary large scale. The experiment involved in total around thousand diagnostic devices and thousand radiologists. AI deployment was associated with additional options in a routine radiologist’s workflow: triage; additional series formed by AI with indication of pathological findings and their classification; report template prepared by AI in accordance with the target clinical task, user feedback on AI performance.A multi-stage methodology for implementing AI into radiological practice that was developed and advanced during the experiment is described in this report.EssentialsA methodology for the AI deployment for non-academic radiological sites excluded more than half of the offered AI solutions that do not fulfill the diagnostic and functional requirementsQuality control of AI should be supported by not only data scientists, IT specialists or engineers, but also by radiologists at all stages of selection and testing.Radiologists need to understand the capabilities, limitations of AI by getting an additional training.
Improved Metagenomic Binning with Transformers
Authors: Shenker-Tauris Nina , Gehrig Jeanette 
Published: February 2022

AbstractTraditional metagenome binning methods cluster contiguous DNA sequences (contigs) based on uncontextualized features of the sequences which ignores both the semantic relationship between genes and the positional embedding of k-mers. This paper presents a novel binning method that addresses these concerns. Firstly, taken from natural language processing literature, a sequence representation model - Bidirectional Encoder Representations from Transformers (BERT) - is utilized to generate semantic and positional contig embeddings. Secondly, two workflows are presented; one which applies a hierarchical density-based clustering algorithm to find metagenomic bins and the other which incorporates contig embedding into a state-of-the-art binner. Experimental results on a publicly available metagenomic dataset show superior clustering for shorter contigs compared to traditionally used tetranucleotide frequency (TNF), reconstruction of up to 17% more high-precision genomes, and improved semantic understanding of contigs.
Optimisation-based modelling for drug discovery in malaria
Authors: Li Yutong , Cardoso-Silva Jonathan , Papageorgiou Lazaros G. , Tsoka Sophia 
Published: February 2022

AbstractThe discovery of new antimalarial medicines with novel mechanisms of action is important, given the ability of parasites to develop resistance to current treatments. Through the Open Source Malaria project that aims to discover new medications for malaria, several series of compounds have been obtained and tested. Analysis of the effective fragments in these compounds is important in order to derive means of optimal drug design and improve the relevant pharmaceutical application. We have previously reported a novel optimisation-based method for quantitative structure-activity relationship modelling, modSAR, that provides explainable modelling of ligand activity through a mathematical programming formulation. Briefly, modSAR clusters small molecules according to chemical similarity, determines the optimal split of each cluster into appropriate regions, and derives piecewise linear regression equations to predict the inhibitory effect of small molecules. Here, we report application of modSAR in the analysis of OSM anti-malarial compounds and illustrate how rules generated by the model can provide interpretable results for the contribution of individual ECFP fingerprints in predicting ligand activity, and contribute to the search for effective drug treatments.
Single Cell Proteomics Using a Trapped Ion Mobility Time-of-Flight Mass Spectrometer Provides Insight into the Post-translational Modification Landscape of Individual Human Cells
Authors: Orsburn Benjamin C. , Yuan Yuting , Bumpus Namandjé N. 
Published: February 2022

AbstractSingle cell proteomics is a powerful tool with potential for markedly enhancing understanding of cellular processes. Previously reported single cell proteomics innovations employ Orbitrap mass spectrometers. In this study we describe the development, optimization, and application of multiplexed single cell proteomics to the analysis of human-derived cells using trapped ion mobility time-of-flight mass spectrometry. This method, denoted as pasefRiQ is an advance as it allows accurate peptide quantification at picogram peptide concentrations. When employing a peptide carrier channel to boost protein sequence coverage, we obtain over 40,000 tandem mass spectra in 30 minutes, while achieving higher sequence coverage of each identified protein than described for SCOPE2. Using NCI-H-358 cells, which are a human bronchioalveolar carcinoma and KRASG12C model cell line, we demonstrate that the level of coverage achieved using this method enables the quantification of up to 1,255 proteins per cell and the detection of multiple classes of post-translational modifications in single cells. Further, when cells were treated with sotorasib, a KRASG12C covalent inhibitor, pasefRiQ revealed cell-to-cell variability in the impact of the drug on the NCI-H-358 cells, providing insight missed by traditional analyses. We provide multiple resources necessary for the application of single cell proteomics to drug treatment studies including tools to reduce cell cycle linked proteomic effects from masking pharmacological phenotypes.Significance StatementThis work describes the establishment of a single cell proteomics method using a time-of-flight mass spectrometer. Through this approach, we demonstrate the confident identification of post- translational modifications in single human-derived cells. Additionally, using a KRASG12C covalent inhibitor as a model compound we show that this method can be used to understand pharmacological responses of single human-derived cultured cells.
Relevance study of vector competence and insecticide resistance in Aedes aegypti laboratory lines
Authors: Wang Lanjiao , Fontaine Albin , Gaborit Pascal , Guidez Amandine , Issaly Jean , Girod Romain , Kazanji Mirdad , Rousset Dominique , Vignuzzi Marco , Epelboin Yanouk , Dusfour Isabelle 
Published: February 2022

AbstractThe urban mosquito species Aedes aegypti is the main vector of arboviruses worldwide. Mosquito control with insecticides is the most prevalent method for preventing transmission in the absence of effective vaccines and available treatments; however, the extensive use of insecticides has led to the development of resistance in mosquito populations throughout the world, and the number of epidemics caused by arboviruses has increased.Three mosquito lines with different resistance profiles to deltamethrin were isolated in French Guiana, including one with the I1016 knock-down resistant allele. Significant differences were observed in the cumulative proportion of mosquitoes with a disseminated chikungunya virus infection over time. In addition, certain genes (CYP6BB2, CYP6N12, GST2, trypsin) were variably overexpressed in the midgut at 7 days after an infectious blood meal in these three lines. Therefore, detoxification enzymes and kdr mutations may contribute to an enhanced midgut barrier and reduced dissemination rate.Our work shows that vector competence for chikungunya virus varied between Ae. aegypti laboratory lines with different deltamethrin-resistance profiles. More accurate verification of the functional association between insecticide resistance and vector competence remains to be demonstrated.ImportanceThree Ae. aegypti lines, isolated from the same collection site, underwent different insecticide selection pressures against deltamethrin under laboratory conditions. As a result, they developed different resistant profiles. In this study, when these lines were fed an artificial infectious blood meal containing chikungunya virus, all three lines including the reference strain showed a high infection rate. There was no statistical difference in infection rate found; however, the dissemination rate of the virus from midgut to head were significantly different. A higher resistance level detected by the WHO test was correlated with a lower viral dissemination rate for each strain. This study presented evidence that the insecticide selection pressure or the existence of insecticide resistance could lead to differences in viral dissemination or even transmission in mosquito populations. We hope that our study can give more insights into understanding the roles of mosquito insecticide resistance on viral transmission.
Comprehensive humoral and cellular immune responses to SARS-CoV-2 variants in diverse Chinese populations: A benefit perspective of national vaccination
Authors: Li Jiwei , Wu Jing , Long Qiuyue , Wu Yanan , Hu Xiaoyi , He Yukun , Jiang Mingzheng , Li Jia , Zhao Lili , Yang Shuoqi , chen Xiaoyong , Wang Minghui , Zheng Jianshi , Wu Fangfang , Wu Ruiliang , Ren Lihong , Bu Liang , Wang Houzhao , Li Ke , Fu Lijuan , Zhang Guojun , Zheng Yali , Gao Zhancheng 
Published: February 2022

AbstractThe emerging SARS-CoV-2 variants have made great challenges to current vaccine and pandemic control strategies. B.1.1.529 (Omicron), which was classified as a variant of concern (VOC) by the World Health Organization on November 26th, 2021, has quickly become the dominant circulating variant and causing waves of infections. It is urgent to understand the current immune status of the general population given that pre-existing immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases suffered a breakthrough infection after vaccination, and 49 vaccinated participants without infection history), we showed that the cross-neutralizing activity against VOCs such as Omicron can be detected in 53 (62.4%) cases, although less potent than against the Wuhan-1 strain (WT), with a 3.9-fold reduction in geometric mean neutralizing titer (GMT) (130.7, 95% CI 88.4-193.3 vs 506, 355.8-719.7, respectively). Subgroup analysis revealed significantly enhanced neutralizing activity against WT and VOCs in Delta convalescent sera. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy donors (p = 0.006), with a GMT of 289.5, 180.9-463.3 and 42.6, 31.3-59, respectively. However, the protective effect against VOCs was weaker in young convalescents (aged < 18y), with a detectable rate of 50% and a GMT of 46.4 against Omicron, similar to vaccinees. The pan-sarbecovirus neutralizing activities were not observed in vaccinated SARS-CoV-1 survivors. A booster dose significantly increased the breadth and magnitude of neutralization against WT and VOCs to different degrees than full vaccination. In addition, we showed that COVID-19 inactivated vaccines can elicit Omicron-specific T cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively. The neutralizing antibody titers declined while T-cell responses remain robust over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.
Zoogeographic patterns on very small spatial scales in rock-dwellingPlectostomasnails from Borneo (Gastropoda: Caenogastropoda: Diplommatinidae)
Authors: Schilthuizen Menno , van Til Angelique 
Published: February 2022

AbstractWe mapped the fine-grained distribution patterns ofPlectostomamicrosnails on two small isolated limestone outcrops in Malaysian Borneo. On both hills, two species were present (P. simplexandP. concinnumon Tandu Batu;P. fraternumandP. concinnumon Tomanggong Besar), but the patterns we found were different. On Tomanggong Besar, the two species occupy different parts of the hill and meet along a narrow hybrid zone that is characterised by a significantly higher rate of predation byAtoposslugs. On Tandu Batu, the two species broadly overlap and do not form hybrids. The predation rate here is the same in both species, regardless of whether they occur in monospecific localities or in mixed localities. Our results show that even small limestone outcrops of a few hundred m in diameter cannot be considered to be uniformly populated by limestone dwelling snails, and a detailed analysis of intra-hill patterns may reveal information on species differences and maintenance.
Reversions to consensus are positively selected in HIV-1 and bias substitution rate estimates
Authors: Druelle Valentin , Neher Richard A. 
Published: February 2022

AbstractHIV-1 is a rapidly evolving virus able to evade host immunity through rapid adaptation during chronic infection. The HIV-1 group M has diversified since its zoonosis into several subtypes at a rate of the order of 10−3 changes per site per year. This rate varies between different parts of the genome and its inference is sensitive to the time scale and diversity spanned by the sequence data used. Higher rates are estimated on short time scales and particularly for within-host evolution, while rate estimates spanning decades or the entire HIV-1 pandemic tend to be lower. The underlying causes of this difference are not well understood.We investigate here the role of rapid reversions toward a preferred evolutionary sequence state on multiple time scales. We show that within-host reversion mutations are under positive selection and contribute substantially to sequence turnover, especially at conserved sites. We then use the rates of reversions and non-reversions estimated from longitudinal within-host data to parametrize a phylogenetic sequence evolution model. Sequence simulation of this model on HIV-1 phylogenies reproduces diversity and apparent evolutionary rates of HIV-1 in gag and pol, suggesting that a tendency to rapidly revert to a consensus-like state can explain much of the time dependence of evolutionary rate estimates in HIV-1.
Loss of RNase J leads to multi-drug tolerance and accumulation of highly structured mRNA fragments in Mycobacterium tuberculosis
Authors: Martini Maria Carla , Hicks Nathan D. , Xiao Junpei , Barbier Thibault , Sixsmith Jaimie , Fortune Sarah M. , Shell Scarlet S. 
Published: February 2022

ABSTRACTDespite the existence of well-characterized, canonical mutations that confer high-level drug resistance to Mycobacterium tuberculosis (Mtb), there is evidence that drug resistance mechanisms are more complex than simple acquisition of such mutations. Recent studies have shown that Mtb can acquire non-canonical resistance-associated mutations that confer survival advantages in the presence of certain drugs, likely acting as stepping-stones for acquisition of high-level resistance. Rv2752c/rnj, encoding RNase J, is disproportionately mutated in drug-resistant clinical Mtb isolates. Here we show that deletion of rnj confers increased tolerance to lethal concentrations of several drugs. RNAseq revealed that RNase J affects expression of a subset of genes enriched for PE/PPE genes and stable RNAs and is key for proper 23S rRNA maturation. Gene expression differences implicated two sRNAs and ppe50-ppe51 as important contributors to the drug tolerance phenotype. In addition, we found that in the absence of RNase J, many short RNA fragments accumulate because they are degraded at slower rates. We show that the accumulated transcript fragments are targets of RNase J and are characterized by strong secondary structure and high G+C content, indicating that RNase J has a rate-limiting role in degradation of highly structured RNAs. Taken together, our results demonstrate that RNase J indirectly affects drug tolerance, as well as reveal the endogenous roles of RNase J in mycobacterial RNA metabolism.
The Yeast Lifespan Machine: a microfluidic platform for automated replicative lifespan measurements
Authors: Thayer Nathaniel H. , Robles Michael , Xu Jun , Schinski Elizabeth L. , Hotz Manuel , Keyser Robert , Millett-Sikking Alfred , Okreglak Voytek , Rogers Jason V. , Waite Adam J. , Wranik Bernd J. , York Andrew G. , McIsaac R. Scott , Gottschling Daniel E. 
Published: February 2022

SummaryThe budding yeast,Saccharomyces cerevisiae, has emerged as a model system for studying the aging processes in eukaryotic cells. However, the full complement of tools available in this organism has not been fully applied, in part because of limitations in throughput that restrict the ability to carry out detailed analyses. Recent advances in microfluidics have provided direct longitudinal observation of entire yeast lifespans, but have not yet achieved the normal scale of operation possible in this model system. Here we present a microfluidic platform, called the Yeast Lifespan Machine, where we combine improvements in microfluidics, image acquisition, and image analysis tools to increase robustness and throughput of lifespan measurements in aging yeast cells. We demonstrate the platform’s ability to measure the lifespan of large populations of cells and distinguish long- and short-lived mutants, all with minimal involvement of the experimenter. We also show that environmental pH is capable of significantly modulating lifespan depending on the growth media, highlighting how microfluidic technologies reveal determinants of lifespan that are otherwise difficult to ascertain.
The stereotype of accountants: using a personality approach to assess the perspectives of laypeople
Authors: Leão Fernanda , Gomes Delfina 
Published: February 2022

PurposeIn the context of Portugal, this study examines the stereotypes of accountants held by laypeople and how they are influenced by financial crises and accounting scandals.Design/methodology/approachTo better understand the social images of accountants, the authors adopt a structural approach based on the big five model (BFM) of personality. The authors test this approach on a Portuguese community sample (N = 727) using a questionnaire survey. The results are analyzed considering the socioanalytic theory.FindingsThe results suggest the existence of a stereotype dominated by features of conscientiousness, which is related to the superior performance of work tasks across job types. This feature comprises the core characteristics of the traditional accountant stereotype, which survives in a context challenged by financial scandals and crises. The findings highlight the social acceptance of accountants as an occupational group but do not suggest the possibility of accountants benefiting from the highest levels of social status when considered in relation to the traditional accountant stereotype.Originality/valueBy combining the BFM and the socioanalytic theory, this study provides a unique theoretical approach to better understand the social images of accountants. The findings demonstrate the suitability of using the BFM to study the social perceptions of accountants. They also indicate a paradox based on the survival of the traditional stereotype. This stereotype appears to be resistant to scandals and financial crisis, instead of being impaired, giving rise to another prototype with concerns about integrity.
Pemex: oil price and financial management in the context of elevated fiscal burden
Authors: Tacuba Angélica 
Published: February 2022

PurposeThe article analyzes how oil price fluctuations are reflected in the management of Petróleos Mexicanos (Pemex) based on its balance sheet (BS) and particularly how oil price fluctuations affect Pemex's corporate income.Design/methodology/approachThe author uses a vector auto-regressive (VAR) model with seven variables for the period 1977–2019. The first variable is the oil price and the others belong to Pemex's BS: total income, sales revenue, operating costs, investment, payment of taxes, duties and contributions (TDC) and the payment of interest on debt.FindingsThe results show that in an environment of elevated fiscal burden that is of an excessive payment of tax by Pemex to the state, the price increases positively affected the income obtained from sales, but that surplus is used primarily to finance the fiscal expenses coming from the TDC, which is associated with the production and commercialization of hydrocarbons; physical and financial investment is disconnected from the evolution of price. Under a fiscal scheme that extracts, on average, 98.46% of Pemex's income, investment is not a priority.Practical implicationsThe findings of the research have important implications for Mexico's energy policy because of affecting the long-term financial and productive sustainability of Pemex.Originality/valueFirst, the study contributes to the literature on oil prices in Mexico by analyzing Pemex's fiscal burden from a corporate finance perspective, an area in which there are few rigorous studies. Second, the study contributes by providing quantitative support for the relationship between oil prices and BS variables through the VAR model.