bluuebunny/crossref_metadata_2025 huggingface dataset:
Serine protease CrKP43 interacts with MAPK and regulates fungal development and mycoparasitism in
Clonostachys chloroleuca
Authors: Lv Binna , Zhao Xue , Guo Yan , Li Shidong , Sun Manhong
Published: October 2023

Serine proteases are a group of important hydrolytic enzymes that play vital roles in various cellular processes in fungi. In this study, the S8 serine protease-encoding gene
CrKP43
was identified in the highly efficient
Clonostachys chloroleuca
67–1 (formerly
C. rosea
67–1) strain, which was markedly upregulated when parasitizing
Sclerotinia sclerotiorum
. The function of
CrKP43
was investigated using gene deletion and complementation, and the results indicated that the lack of
CrKP43
resulted in deformed fungal hyphae and cell morphology, inhibition of conidiation, and decreased antagonistic activity toward the pathogenic fungus
Fusarium oxysporum
f. sp.
cucumerinum
. Moreover, the mutants displayed much weaker mycoparasitic ability to
S. sclerotiorum
sclerotia and lower control efficiency against soybean
Sclerotinia
rot compared with the wild-type strain. All biological characteristics and biocontrol activities were recovered when the
CrKP43
gene was reinserted into the fungus. Using qRT-PCR analysis and protein-protein interaction assays, it was further proved that the CrKP43 protein interacted with the mitogen-activated protein kinase (MAPK) Crmapk, suggesting serine proteases might be involved in the mycoparasitism of
C. chloroleuca
with the regulation of Crmapk. The findings improve our knowledge of serine proteases and their regulation in mycoparasites and help to illuminate the mechanisms underlying mycoparasitism of
C. chloroleuca
.

IMPORTANCE

Mycoparasites play important roles in the biocontrol of plant fungal diseases, during which they secret multiple hydrolases such as serine proteases to degrade their fungal hosts. In this study, we demonstrated that the serine protease CrKP43 was involved in
C. chloroleuca
development and mycoparasitism with the regulation of Crmapk. To the best of our knowledge, it is the first report on the functions and regulatory mechanisms of serine proteases in
C. chloroleuca
. Our findings will provide new insight into the regulatory mechanisms of serine proteases in mycoparasites and contribute to clarifying the mechanisms underlying mycoparasitism of
C. chloroleuca
, which will facilitate the development of highly efficient fungal biocontrol agents as well.
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

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

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

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

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

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

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

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

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

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

Aim

We 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.

Methods

3919 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.

Results

The 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).

Conclusions

A 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

Introduction

Prescribers 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.

Method

The 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).

Analysis

Quantitative 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.

Results

Implemented 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.

Conclusion

Implemented changes improved reliability, efficiency and perceived safety of the test results monitoring system while ensuring patient satisfaction.
Does virtual consultation between primary and specialised care improve healthcare quality? A scoping review of healthcare quality domains assessment
Authors: Marco-Ibáñez Almudena , Aguilar-Palacio Isabel , Aibar Carlos
Published: October 2023

Background

Virtual consultation has been proposed as a promising tool to improve the coordination and quality of healthcare between primary and specialised care. However, despite its potential facilitators, the evidence on the usefulness of virtual consultation for improving healthcare quality domains is fragmented and unclear. This scoping review aims to assess the impact of virtual consultation on different healthcare quality domains.

Material and methods

We conducted a scoping review with a rigorous search strategy on PubMed, EMBASE and Cochrane Library databases. The inclusion criteria were original articles, reviews, meta-analyses or letters to the editor, published between 1 January 2017 and 24 June 2022, and available in English, Spanish or French. For each of the articles selected, we identified the addressed healthcare quality domains, their facilitators and barriers, areas of improvement and data gaps. We have adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review reporting standards.

Results

1284 manuscripts were retrieved. Finally, 235 papers were included in this review, most of which were original, descriptive studies. The most evaluated quality domain was effectiveness (223 articles). Safety and patient-centred care were the least evaluated. Simultaneous assessment of more than one domain was observed in 117 papers, being effectiveness and timeliness the most frequent combination. Our analysis revealed that virtual consultation is in development and underused. This tool has the potential to improve access to specialised care and enhance coordination between professionals.

Conclusions

Virtual consultation has the potential to provide effective, efficient, equitable and timely attention. However, its contribution to safety and patient-centered care needs further evaluation. Our review emphasises the need for more rigorous research and standardised quality assessment criteria to obtain robust evidence on the usefulness of virtual consultation for improving healthcare quality domains.
Association of COVID-19 with respiratory syncytial virus (RSV) infections in children aged 0–5 years in the USA in 2022: a multicentre retrospective cohort study
Authors: Wang Lindsey , Davis Pamela B , Berger Nathan , Kaelber David C , Volkow Nora , Xu Rong
Published: October 2023

Objective

To investigate whether COVID-19 infection was associated with increased risk for incident respiratory syncytial virus (RSV) infections and associated diseases among young children that might have contributed to the 2022 surge of severe paediatric RSV cases in the USA.

Design

This is a retrospective population-based cohort study. Five outcomes were examined, including overall RSV infection, positive lab test-confirmed RSV infection, clinically diagnosed RSV diseases, RSV-associated bronchiolitis and unspecified bronchiolitis. Risk ratio (RR) and 95% CI of the outcomes that occurred during the 2022 and 2021 RSV seasons were calculated by comparing propensity-score matched cohorts.

Setting

Nationwide multicentre database of electronic health records (EHRs) of 61.4 million patients in the USA including 1.7 million children 0–5 years of age, which was accessed through TriNetX Analytics that provides web-based and secure access to patient EHR data from hospitals, primary care and specialty treatment providers.

Participants

The study population consisted of 228 940 children of 0–5 years with no prior RSV infection who had medical encounters in October 2022. Findings were replicated in a separate study population of 370 919 children of 0–5 years with no prior RSV infection who had medical encounters in July 2021–August 2021 during a non-overlapping time period.

Results

For the 2022 study population (average age 2.4 years, 46.8% girls, 61% white, 16% black), the risk for incident RSV infection during October 2022–December 2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (RR 1.40, 95% CI 1.27 to 1.55); and among children aged 0–1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR 1.40, 95% CI 1.21 to 1.62). For the 2021 study population (average age 2.2 years, 46% girls, 57% white, 20% black), the risk for incident RSV infection during July 2021–December 2021 was 4.85% for children with prior COVID-19 infection, higher than 3.68% for the matched children without COVID-19 (RR 1.32, 95% CI 1.12 to 1.56); and 7.30% for children aged 0–1 year with prior COVID-19 infection, higher than 4.98% for matched children without (RR 1.47, 95% CI 1.18 to 1.82).

Conclusion

COVID-19 was associated with a significantly increased risk for RSV infections among children aged 0–5 years in 2022. Similar findings were replicated for a study population of children aged 0–5 years in 2021. Our findings suggest that COVID-19 contributed to the 2022 surge of RSV cases in young children through the large buildup of COVID-19-infected children and the potential long-term adverse effects of COVID-19 on the immune and respiratory system.
Congenital anaemia associated with loss-of-function variants in DNA polymerase epsilon 1
Authors: Takeuchi Ichiro , Tanase-Nakao Kanako , Ogawa Ayame , Sugawara Tohru , Migita Osuke , Kashima Makoto , Yamazaki Touko , Iguchi Akihiro , Naiki Yasuhiro , Uchiyama Toru , Tamaoki Junya , Maeda Hiroki , Shimizu Hirotaka , Kawai Toshinao , Taniguchi Kosuke , Hirata Hiromi , Kobayashi Makoto , Matsumoto Kimikazu , Naruse Kiyoshi , Hata Kenichiro , Akutsu Hidenori , Kato Takashi , Narumi Satoshi , Arai Katsuhiro , Ishiguro Akira
Published: October 2023

DNA polymerase epsilon (Pol ε), a component of the core replisome, is involved in DNA replication. Although genetic defects of Pol ε have been reported to cause immunodeficiency syndromes, its role in haematopoiesis remains unknown. Here, we identified compound heterozygous variants (p.[Asp1131fs];[Thr1891del]) in
POLE
, encoding Pol ε catalytic subunit A (POLE1), in siblings with a syndromic form of severe congenital transfusion-dependent anaemia. In contrast to Diamond-Blackfan anaemia, marked reticulocytopenia or marked erythroid hypoplasia was not found. Their bone marrow aspirates during infancy revealed erythroid dysplasia with strongly positive TP53 in immunostaining. Repetitive examinations demonstrated trilineage myelodysplasia within 2 years from birth. They had short stature and facial dysmorphism. HEK293 cell-based expression experiments and analyses of patient-derived induced pluripotent stem cells (iPSCs) disclosed a reduced mRNA level of Asp1131fs-POLE1 and defective nuclear translocation of Thr1891del-POLE1. Analysis of iPSCs showed compensatory mRNA upregulation of the other replisome components and increase of the TP53 protein, both suggesting dysfunction of the replisome. We created
Pole
-knockout medaka fish and found that heterozygous fishes were viable, but with decreased RBCs. Our observations expand the phenotypic spectrum of the Pol ε defect in humans, additionally providing unique evidence linking Pol ε to haematopoiesis.
Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
Authors: Graham Neil , Zimmerman Karl , Heslegrave Amanda J , Keshavan Ashvini , Moro Federico , Abed-Maillard Samia , Bernini Adriano , Dunet Vincent , Garbero Elena , Nattino Giovanni , Chieregato Arturo , Fainardi Enrico , Baciu Camelia , Gradisek Primoz , Magnoni Sandra , Oddo Mauro , Bertolini Guido , Schott Jonathan M , Zetterberg Henrik , Sharp David
Published: October 2023

Background

Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.

Methods

Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls.

Results

Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.

Conclusions

Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
Reperfusion and cytoprotective agents are a mutually beneficial pair in ischaemic stroke therapy: an overview of pathophysiology, pharmacological targets and candidate drugs focusing on excitotoxicity and free radical
Authors: Xu Xiumei , Chen Mingyu , Zhu Dongya
Published: October 2023

Stroke is the second-leading cause of death and the leading cause of disability in much of the world. In particular, China faces the greatest challenge from stroke, since the population is aged quickly. In decades of clinical trials, no neuroprotectant has had reproducible efficacy on primary clinical end points, because reperfusion is probably a necessity for neuroprotection to be clinically beneficial. Fortunately, the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke (AIS) therapy. Brain cytoprotective agents can prevent detrimental effects of ischaemia, and therefore ‘freeze’ ischaemic penumbra before reperfusion, extend the time window for reperfusion therapy. Because reperfusion often leads to reperfusion injury, including haemorrhagic transformation, brain oedema, infarct progression and neurological worsening, cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion injuries. Therefore, reperfusion and cytoprotective agents are a mutually beneficial pair in AIS therapy. In this review, we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS, focusing on excitotoxicity and free radicals. We discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials, highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.
Multi-bit quantum random number generator from path-entangled single photons
Authors: Shafi K. Muhammed , Chawla Prateek , Hegde Abhaya S. , Gayatri R. S. , Padhye A. , Chandrashekar C. M.
Published: October 2023

Measurement outcomes on quantum systems exhibit inherent randomness and are fundamentally nondeterministic. This has enabled quantum physics to set new standards for the generation of true randomness with significant applications in the fields of cryptography, statistical simulations, and modeling of the nondeterministic behavior in various other fields. In this work, we present a scheme for the generation of multi-bit random numbers using path-entangled single photons. For the experimental demonstration, we generate a path-entangled state using single photons from spontaneous parametric down-conversion (SPDC) and assign a multi-qubit state for them in path basis. One-bit and two-bit random numbers are then generated by measuring entangled states in the path basis. In addition to passing the NIST tests for randomness, we also demonstrate the certification of quantumness and self-certification of quantum random number generator (QRNG) using Clauser, Horne, Shimony and Holt (CHSH) inequality violation. We also record the significantly low autocorrelation coefficient from the raw bits generated and this along with CHSH violation rules out multi-photon events and ensure the protection from photon splitting attack. Distribution of photons along multiple paths resulting in multiple bits from one photon extends the limit on bit generation rate imposed by the detection dead time of the individual detector. Thus, the path-entangled states can generate higher bitrates compared to scheme using entangled photon pair which are limited by the coincidence counts. We demonstrate this by generating a high rate of about 80 Mbps when the single photon detector saturates at around 28 Mcps and still show violation of CHSH inequality.
First-principles study of structural, electronic and optoelectronic properties of Ag-doped Cu2O alloys: TB-mBJ insights
Authors: Monir Mohammed El Amine , Baltach Hadj , Al-Maaitah Ibtisam F. , Al-Maaitah A. F. , Laref Amel
Published: October 2023

The structural, electronic and optical properties of Cu[Formula: see text]Ag[Formula: see text]O alloys ([Formula: see text], 0.25, 0.50, 0.75 and 1) have been investigated under the framework of the density functional theory (DFT), where the exchange and correlation potential is defined by the generalized gradient approximation of TB-mBJ (TB-mBJ-GGA). The equilibrium lattice constant ([Formula: see text]), bulk modulus ([Formula: see text]) and its first-pressure derivative ([Formula: see text]) are determined for each Cu[Formula: see text]Ag[Formula: see text]O alloys ([Formula: see text], 0.25, 0.50, 0.75 and 1). Based on the equilibrium lattice parameters, the electronic structure of Ag-doped Cu2O alloys is investigated in order to identify the electronic behavior of each compound; this leads to the fact that all Cu2O, Cu[Formula: see text]Ag[Formula: see text]O, CuAgO, Cu[Formula: see text]Ag[Formula: see text]O and Ag2O compounds are semiconductors. Furthermore, the optical properties of these compounds are calculated such as the complex dielectric constant, the complex refractive index, the absorption coefficient and the optical reflectivity.
Phase transition behaviors of Al nanoparticles with low oxidation degree: A molecular dynamics study
Authors: Liu Yi , Xu Jiangtao , Liu Pingan
Published: October 2023

In this study, the ReaxFF reactive force field is applied to simulate the melting and annealing behaviors of aluminum (Al) nanoparticles (ANP) by molecular dynamics (MD) simulations. Potential energy, specific heat and FCC lattice number are used to study the thermal behavior of the entire phase transition process. First, the melting and solidification process of 3[Formula: see text]nm cubic Al and Al2O3 models under constant-pressure/temperature ensemble (NPT) system was simulated without boundary, and the steady-state simulation was discussed at specific temperature points. The non-boundary simulation proved the effectiveness of the Reaxff reactive force field for ANP phase transition simulations. It is confirmed that the physical properties of Al and Al2O3 could be effectively reflected in the MD simulations. ANP with low oxidation degree cannot be completely ignored in engineering applications. The existence of oxide layer hinders the annealing behavior. Therefore, this study also carried out an additional simulation process of 6 nm ANP and its oxide particles in canonical ensemble (NVT). Those obtained results show that a small amount of oxide layer can greatly change the thermal properties of ANP. If the surface of ANP is isolated, then its melting point could be increased by at least 30[Formula: see text]K.
Sustainable porcelain ceramics production using local raw materials and recycled automotive glass
Authors: Djemli A. , Belhouchet H. , Faci A. , Ghebouli M. A. , Bouferrache K. , Slimani Y. , Chihi T. , Ghebouli B. , Fatmi M. , Algethami Norah , Mouhammad Saif A. , Alomairy Sultan
Published: October 2023

The main objective of this research is the explanation of the replacement of feldspar limestone imported from Spain with recycled automotive glass, in order to reduce waste and promote environmental sustainability. Details and efforts of making porcelain ceramics from local raw materials such as quartz, kaolin and glass are also given. Replacing the feldspar with reclaimed automotive glass shows the effect of the Na2O and CaO solvents contained in the glass on the sintering and crystallization of the studied porcelain. The results showed that the added glass contributes to the reduction of the density and the acceleration of the sintering process, by occupying the sites of the open spaces, observed in the samples not containing feldspars. By reaching a nonporous ratio at a temperature of 1000∘C, the melting of the material is accelerated due to the dissolved oxides it contains, in addition to the linear shrinkage rate in samples that contain a lot of glass reaching the normal level of porcelain (about 12%) at low temperature compared to ordinary porcelain.
The Precipitation Concentration in the Cheliff Watershed, Algeria: A Critical Analysis for Sustainable Water Resource Management
Authors: BRAHIMI Samiha , MEDDI Hind , MEDDI Mohamed , HALLOUZ Faiza , SAAED HAMOUDI Abdelamir
Published: October 2023

In this study, a statistical analysis of historical and projected values of the annual, seasonal, and supra-seasonal precipitation concentration index (PCI) was conducted for different stations in the Cheliff watershed. Statistical methods such as breakpoint and trend analysis using Pettitt and Mann–Kendall tests were used for the PCI values of annual, monthly, and supra-seasonal precipitation data between 1950 and 2014. The PCI values varied between 14.24% and 24.86% annually, between 10.75% and 18.74% seasonally, and between 11.23% and 26.98% supra-seasonally. According to the Pettitt and Mann–Kendall tests, there was an insignificant change in precipitation distribution during the study period. Spatial analysis using the inverse distance weighting (IDW) method confirmed the minor variability in precipitation distribution in the study area. The Pearson correlation coefficient between oscillation indices and PCI values at different scales showed significant values with the Mediterranean Oscillation index (MOi), North Atlantic Oscillation (NAO), and Western Mediterranean Oscillation index (WeMOi), highlighting their potential influence on annual PCI values. For the climate projection scenarios, projected PCI values align with historical PCI values. Application of Pettitt and Mann-Kendall tests to the projected PCI series shows that there will not be a significant change in future precipitation distribution.
Rare Category Analysis for Complex Data: A Review
Authors: Zhou Dawei , He Jingrui
Published: October 2023

Though the sheer volume of data that is collected is immense, it is the rare categories that are often the most important in many high-impact domains, ranging from financial fraud detection in online transaction networks to emerging trend detection in social networks, from spam image detection on social media platforms to rare disease diagnosis in medical decision support systems. The unique challenges of rare category analysis include (1) the highly skewed class distribution; (2) the non-separable nature of the rare categories from the majority classes; (3) data and task heterogeneity; and (4) the time-evolving property of the input data sources. This survey reviews state-of-the-art techniques used in complex rare category analysis, where the majority classes have a smooth distribution while the minority classes exhibit the compactness property in the feature space or subspace. Rare category analysis aims to identify, characterize, represent, and interpret anomalies that not only show statistical significance but also exhibit interesting patterns (e.g., compactness, high-order structures, showing in a burst). We introduce our study, define the problem setting, and describe the unique challenges of complex rare category analysis. We then present a comprehensive review of recent advances that are designed for this problem setting, from rare category exploration without any label information to rare category exposition that characterizes rare examples with a compact representation, from the representation of rare patterns in a salient embedding space to the interpretation the prediction results and providing relevant clues for the end-users’ interpretation. Finally we discuss potential challenges and shed light on the future directions for complex rare category analysis.

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