bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effective complete genome sequencing using the MinION platform for identification of recombinant enteroviruses
Authors: Chien Yeh-Sheng , Chen Feng-Jui , Wu Han-Chieh , Lin Chieh-Hua , Chang Wen-Chiung , Perera David , Yang Jyh-Yuan , Lee Min-Shi , Liao Yu-Chieh 
Published: October 2023

ABSTRACT
Enteroviruses (EVs) are a group of viruses that cause various human illnesses. While the CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) method can generate VP1 gene fragments for enterovirus genotyping, it is unable to detect recombinant strains. Recent advances in viral genome sequencing using next-generation sequencing technologies have enabled comprehensive analyses. However, the high cost poses a challenge for widespread adoption. To address this issue, this study proposes a cost-effective approach for generating complete enterovirus genome sequences using the Oxford Nanopore MinION sequencer. This protocol not only facilitates the generation of accurate genome sequences for various enterovirus strains but also allows for the differentiation of co-infections from viral isolates. In addition, the method can generate polyprotein sequences as well as peptide sequences of the upstream ORF (uORF) whose expression can impact virus infection. Through the analysis of complete enterovirus genomes, this study successfully identified seven enterovirus A71 isolates obtained during the 2018 enterovirus outbreak in Malaysia and Taiwan as recombinants between enterovirus A71 and coxsackievirus A2. Furthermore, our study has made a significant discovery by establishing a strong correlation between uORF trees and the epidemics of EVA71. This finding highlights the potential of uORF sequences as valuable indicators for monitoring and understanding the spread of EVA71 infections. We also identified notable amino acid changes in the transmembrane domain of the uORF protein within a newly identified lineage. These findings provide crucial insights into the molecular characteristics and evolutionary dynamics of EVA71, offering valuable information for future research and intervention strategies.

IMPORTANCE
By employing a cost-effective approach for complete genome sequencing, the study has enabled the identification of novel enterovirus strains and shed light on the genetic exchange events during outbreaks. The success rate of genome sequencing and the scalability of the protocol demonstrate its practical utility for routine enterovirus surveillance. Moreover, the study’s findings of recombinant strains of EVA71 and CVA2 contributing to epidemics in Malaysia and Taiwan emphasize the need for accurate detection and characterization of enteroviruses. The investigation of the whole genome and upstream ORF sequences has provided insights into the evolution and spread of enterovirus subgenogroups. These findings have important implications for the prevention, control, and surveillance of enteroviruses, ultimately contributing to the understanding and management of enterovirus-related illnesses.
Natural transformation and cell division delay in competent
Staphylococcus aureus
Authors: Morgene Fedy , Rizoug Zeghlache Célia , Feng Shi Yuan , Hauck Yolande , Mirouze Nicolas 
Published: October 2023

ABSTRACT

Genetic competence for natural transformation, considered one of the three main mechanisms leading to horizontal gene transfer in bacteria, is able to promote evolution, through genomic plasticity, and foster antibiotic resistance and virulence factors spreading. Conserved machinery and actors required to perform natural transformation have been shown to accumulate at different cellular localizations depending on the model organism considered. In this study, we investigate the transformation apparatus composition, localization, and dynamics in the human pathogen
Staphylococcus aureus
. We particularly show that most of the natural transformation actors co-localize in clusters. We also reveal that the localization of natural transformation proteins is dynamic, following the cell cycle. Ultimately, the natural transformation apparatus is preferentially established in the vicinity of the division septum. All these results demonstrate that DNA binding, uptake, and recombination are spatially and temporally coordinated to ensure
S. aureus
natural transformation. Finally, we hypothesize that
S. aureus
competent cells would initiate and then block cell division to ensure the success of natural transformation before the final constriction of the cytokinetic ring.

IMPORTANCE

Natural transformation, considered one of the three main mechanisms leading to horizontal gene transfer in bacteria, is able to promote genomic plasticity and foster antibiotic resistance spreading. Conserved machinery and actors required to perform natural transformation have been shown to accumulate at different cellular localizations depending on the model organism considered. Here, we show in the human pathogen
Staphylococcus aureus
that DNA binding, uptake, and recombination are spatially and temporally coordinated to ensure
S. aureus
natural transformation. We also reveal that localization of natural transformation proteins occurs in the vicinity of the division septum allowing
S. aureus
competent cells to block cell division to ensure the success of natural transformation before the final constriction of the cytokinetic ring.
Amino acid 17 in QRDR of Gyrase A plays a key role in fluoroquinolones susceptibility in mycobacteria
Authors: Wang Shuai , Zhang Jingran , Hameed H. M. Adnan , Ding Jie , Guan Ping , Fang Xiange , Peng Jiacong , Su Biyi , Ma Shangming , Tan Yaoju , M. Cook Gregory , Zhang Guoliang , Lin Yongping , Zhong Nanshan , Hu Jinxing , Liu Jianxiong , Zhang Tianyu 
Published: October 2023

ABSTRACT

The polymorphism at amino acid 17 of quinolone resistance-determining region of GyrA has been stated with a potential role in fluoroquinolone susceptibility in different mycobacterial species. However, no study has provided dependable evidence so far. Here, we verified that gene-edited
Mycobacterium abscessus
mutants bearing Ser/Gly at this position were more susceptible to fluoroquinolones than their parent strain and the revertant that supports mycobacteria containing Ser/Gly at this position were more susceptible to fluoroquinolones than those containing Ala.

IMPORTANCE

Fluoroquinolones (FQs) play a key role in the treatment regimens against tuberculosis and non-tuberculous mycobacterial infections. However, there are significant differences in the sensitivities of different mycobacteria to FQs. In this study, we proved that this is associated with the polymorphism at amino acid 17 of quinolone resistance-determining region of Gyrase A by gene editing. This is the first study using CRISPR-associated recombination for gene editing in
Mycobacterium abscessus
to underscore the contribution of the amino acid substitutions in GyrA to FQ susceptibilities in mycobacteria.
Infection with Trematodes in Littorina obtusata Snails (Gastropoda: Littorinidae) with Different Shell Color Genotypes
Authors: Kozminsky E. V. 
Published: October 2023

Abstract
The prevalence of infection with trematode parthenitae was studied in Littorina obtusata littoral periwinkles with different shell color genotypes. Activities of genes responsible for a purple or orange single-pigment background shell coloration was not found to affect the prevalence of trematode infection in periwinkles. In L. obtusata with a yellow-purple background shell color and a pattern of white pigment spots on the shell, the prevalence of infection with Microphallus piriformes and M. pygmaeus was lower than the theoretical expectation. The prevalence of infection in periwinkles with purple, orange, or white stripes on the shell did not differ from that of unstripped periwinkles. The differences found were presumably associated with genetically determined susceptibility to infection. Possible consequences of differential infection with trematodes in periwinkles with different shell color genotypes are discussed in terms of the stability of parasitic systems and possible changes in the phenotypic structure of the host population.
Endobiotic Ciliates from the Rumen of the European Bison Bison Bonasus (Linnaeus, 1758) from the Vologda Oblast of Russia
Authors: Kornilova O. A. , Chistyakova L. V. , Gusarov I. V. 
Published: October 2023

Abstract
The fauna of endobiotic ciliates of the rumen of the European bison Bison bonasus from the Vologda oblast of Russia was investigated. In the studied bisons, 12 species of trichostomatids (Trichostomatia, Litostomatea) were found, ten of which were from the family Ophryoscolecidae and two species were from the family Isotrichidae. A high similarity of ciliate faunas in the rumen of different bison individuals in the studied population was noted. A comparative analysis of data on the species diversity and number of endobiotic ciliates in the rumen of various representatives of the genus Bison from different habitats was carried out.
Long-Chain Alkylphenol Biodegradation Potential of Soil Ascomycota
Authors: Kuzikova I. L. , Medvedeva N. G. 
Published: October 2023

Abstract
A total of 11 ascomycete strains destructing technical nonylphenol (NP) and 4-tert-octylphenol (4-t-OP) were isolated from NP-contaminated soddy-podzolic loamy soil (Leningrad Region, Russia). The isolates proved capable of degrading NP and 4-t-OP at a high load (300 mg/L). The most efficient Fusarium solani strain 8F degraded alkylphenols (APs) both in cometabolic conditions and in the absence of additional carbon and energy sources. A decrease in APs was due to biodegradation or biotransformation by the strain and, to a minor extent, absorption by fungal cells. NP and 4-t-OP half-lives were, respectively, 3.5 and 6.4 h in cometabolic conditions and 9 and 19.7 h in the absence of additional carbon and energy sources. Amounts of the lipid peroxidation product malondialdehyde (MDA) and reduced glutathione (GSH) increased during NP and 4-t-OP biodegradation in cometabolic conditions by 1.7 and 2 times, respectively, as compared with a control. A high GSH level in F. solani 8F cells potentially implicated the metabolite in both AP biodegradation and strain resistance to oxidative stress. The study is the first to report on the NP and 4-t-OP degradation by the ascomycete F. solani in cometabolic conditions and in the absence of additional carbon and energy sources. The high AP degradation potential of soil ascomycetes was assumed to provide a basis for new environmentally safe bioremediation technologies for purification of soils and natural and waste waters contaminated with endocrine disruptors.
Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic Lupus Erythematosus
Authors: Cheldieva F. A. , Reshetnyak T. M. , Shumilova A. A. , Nurbaeva K. S. , Cherkasova M. V. , Lila A. M. , Nasonov E. L. 
Published: October 2023

Abstract
The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis—4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels ≥ 6 and ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.
Are the Goals of Therapy Achievable in Patients with Rheumatoid Arthritis Receiving Upadacitinib in Real Clinical Practice?
Authors: Amirdzhanova V. N. , Karateev A. E. , Pogozheva E. Yu. , Filatova E. S. , Samigullina R. R. , Mazurov V. I. , Anoshenkova O. N. , Lapkina N. A. , Baranov A. A. , Grineva T. Yu. , Lila A. M. , Nasonov E. L. 
Published: October 2023

Abstract
The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28(ESR), DAS28(CRP), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient’s RAPID-3 index; the level of depression and anxiety to the HADS scale. The effectiveness of therapy was evaluated after 3 (n = 45) and 6 (n = 31) months of UPA therapy. Remission or low activity of the disease by 3 months of therapy was achieved by most patients: remission of 69.8% of patients, low activity of the disease—16.3% of patients. Moderate or high activity persisted in 13.9% of patients. By the 6th month of UPA therapy, the number of remissions reached 90%, low activity 3.3%, moderate activity persisted in 6.7% of patients, high activity of the disease was not in any patient. 20% improvement in function was achieved in 71.8% of patients by the 3rd month of therapy and in 77.8% by the 6th month of treatment; the difference in average HAQ values by the 3rd month of therapy was 0.38 points, by the 6th month—0.58 points. After 3 months of follow—up, 31.1% of patients continued taking GC, by 6 months—24.2%. The dose of GC was reduced from an average of 7.23 to 5.6 mg/s. The percentage of patients requiring NSAIDs decreased from 95.2 to 35.6% and 33.3%, respectively. DMARDs continued to be received by 75.6% of patients by 3 months and 69.7% by 6 months of follow-up. Achieving remission or low activity of the disease in patients with RA receiving UPA in real clinical practice is possible in most patients. A rapid decrease in inflammatory activity is accompanied by a significant improvement in the functional state and quality of life of patients. UPA therapy reduces the need for the use of NSAIDs and reduces the dose of GC in a third of patients.
Contributing Factors of Diabetes Mellitus among Patients with Gout (Results of the Long-Term Prospective Study)
Authors: Zheliabina O. V. , Eliseev M. S. , Glukhova S. I. , Nasonov E. L. 
Published: October 2023

Abstract
It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m2; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m2; serum uric acid level (sUA) ≥ 420 µmol/L and ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98–9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50–4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02–5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19–4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11–0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21–1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 μmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.
Subset of retinoblastoma tumours is associated with
BRCA1/2
mutations
Authors: Kim Yong Joon , Park Hyo Song , Youk Jeonghwan , Han Jung Woo , Byeon Suk Ho , Kim Sung Soo , Ju Young Seok , Lee Christopher Seungkyu 
Published: October 2023

Background
We investigated the potential association between pathogenic BRCA1/2 variants and retinoblastoma pathogenicity.

Methods

In this single-centre, retrospective case series, we performed hereditary cancer panel tests using blood samples for patients with retinoblastoma diagnosed between March 2017 and October 2021. Bioinformatics prediction tools were then used to conduct in silico pathogenicity assessments for patients with
BRCA1/2
family variants, in addition to the American College of Medical Genetics and Genomics (ACMG) variant classification. One patient with a germline
BRCA1
variant was analysed with whole-genome sequencing (WGS), mutational signature analysis and methylation analysis for
RB1
and
BRCA
using the patient’s tumour and blood samples.

Results

Of 30 retinoblastoma patients who underwent panel sequencing, six (20%) were found to carry germline variants in the BRCA1/2 or BRIP1 genes. Among these six patients, two had pathogenic or likely pathogenic variants as per the ACMG variant classification. Additionally, three patients showed potential pathogenic BRCA1/2 family variants through further analysis with alternative bioinformatics prediction tools. In the WGS analysis of a tumour from a patient with a germline likely pathogenic
BRCA1
variant in one allele, we observed the loss of one RB1 allele due to a large deletion. No somatic non-synonymous mutations or frameshift indels were detected in the RB1 locus of the remaining allele. This sample also showed
BRCA1
gene promoter hypermethylation in the tumour, indicating additional epigenetic silencing.

Conclusion

This study demonstrated that some retinoblastoma patients harboured germline
BRCA1/2
family variants, which may be associated with the development of retinoblastoma along with
RB1
mutations.
Prediction of visual field progression with serial optic disc photographs using deep learning
Authors: Mohammadzadeh Vahid , Wu Sean , Davis Tyler , Vepa Arvind , Morales Esteban , Besharati Sajad , Edalati Kiumars , Martinyan Jack , Rafiee Mahshad , Martynian Arthur , Scalzo Fabien , Caprioli Joseph , Nouri-Mahdavi Kouros 
Published: October 2023

AimWe tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up.Methods3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24–2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy.ResultsThe average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and –3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5–11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812–0.913) and 80.0% (73.9%–84.6%). When only fast-progressing eyes were considered (MD rate < –1.0 dB/year), AUC increased to 0.926 (0.857–0.994).ConclusionsA deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.
Implementing a safer and more reliable system to monitor test results at a teaching university-affiliated facility in a family medicine group: a quality improvement process report
Authors: Dorimain Marie-Victoria , Plouffe-Malette Mireille , Paquette Manon , Bériault Karine 
Published: October 2023

IntroductionPrescribers have the medicolegal responsibility to ensure a sufficiently reliable system is in place to securely monitor the process of efficiently communicating laboratory results. With added complexity of technologies such as electronic medical record systems, few studies address the monitoring, verification and improvement of test results follow-up especially within a teaching facility including resident prescribers.MethodThe main goal of this quality improvement project was to ensure safety of care through reliable test results follow-up and adapting processes to available technology by (1) implementing an improved, more reliable and efficient system for tracking test results in the setting; and (2) increasing perceived reliability of test results monitoring system of prescribers in the clinical setting. Through three Plan-Do-Study-Act cycles, changes were implemented: (1) family medicine residents recognised as prescribers; (2) connection of prescribers to regional techno-centre; and (3) computer protocol eliminating duplicates. Patients and clinical staff completed surveys (satisfaction, perceived safety and reliability).AnalysisQuantitative and qualitative data were collected, reported incidents, requested prescriptions and received results and time spent communicating normal results. Immediate feedback from prescribers and staff members was considered to improve the process. Microsoft Excel software was used to calculate mean and SD of error rate. Shewhart chart rules were used to determine special cause of change and sustainability.ResultsImplemented changes led to decrease in mean error rate (from 6.1% to 1.9%), variation of range (from 2.7–12.1% to 0–4.8%) and SD (from 2.1% to 1.2%). The improvement is sustained over 24 months after the last cycle. 100% of the 30 patients surveyed were satisfied with the changes implemented. Prescribers (75% response rate) including residents (15.8% response rate) perceived the improved system to be safer, more reliable and efficient.ConclusionImplemented changes improved reliability, efficiency and perceived safety of the test results monitoring system while ensuring patient satisfaction.