bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric ultrasound evaluation of liver fibrosis, steatosis, and viscosity in patients with chronic liver disease
Authors: Minciuna Iulia , Taru Madalina , Fodor Andreea , Nicoara Farcau Oana , Fischer Petra , Radu Corina , Lupsor-Platon Monica , Stefanescu Horia , Procopet Bogdan 
Published: February 2024

Aims: This study assessed the effectiveness of three ultrasound-based techniques (2D-SWE.PLUS, Att.PLUS, Vi.PLUS) for non-invasive evaluation of liver fibrosis, steatosis, and inflammation in chronic liver disease (CLD) patients.Materials and methods: Involving 209 consecutive compensated CLD patients, the study compared these ultrasound methods from Aixplorerwith standard Vibration-controlled Transient Elastography (VCTE) and Controlled Attenuation Parameter (CAP) from Fibroscan, alongside non-invasive serological markers.Results: High validity rates were observed in measurements: 99% for VCTE, 89% for 2D-SWE.PLUS/Vi.PLUS, and 96.6% for Att.PLUS. 2D-SWE.PLUS showed a strong correlation with VCTE (R=0.91) and excelled at a lower Stability Index (80%), with optimal cut-offs for moderate and severe fibrosis at 8 kPa and 10 kPa, respectively. 2D-SWE.PLUS was superior to Fib4, eLIFT, APRI, BARD, and NFS in detecting advanced CLD. Att.PLUS moderately correlated with CAP (R=0.47) for steatosis grades, while Viscosity was highly effective in identifying significant fibrosis (AUC=0.87) but less so for inflammation.Conclusions: 2D-SWE.PLUS demonstrated superior diagnostic precision in liver fibrosis, exceeding other non-invasive markers. Att.PLUS was relatively accurate for liver steatosis, and viscosity more effectively indicated fibrosis stages than inflammation in CLD patients.
Single-cell RNA-seq revealed heterogeneous responses and functional differentiation of hemocytes against white spot syndrome virus infection in
Litopenaeus vannamei
Authors: Cui Chuang , Tang Xiaoqian , Xing Jing , Sheng Xiuzhen , Chi Heng , Zhan Wenbin 
Published: February 2024

ABSTRACT

Shrimp hemocytes are the vital immune cells participating in innate immune response to defend against viruses. However, the lack of specific molecular markers for shrimp hemocyte hindered the insightful understanding of their functional clusters and differential roles in combating microbial infections. In this study, we used single-cell RNA sequencing to map the transcriptomic landscape of hemocytes from the white spot syndrome virus (WSSV)-infected
Litopenaeus vannamei
and conjointly analyzed with our previous published single-cell RNA sequencing technology data from the healthy hemocytes. A total of 16 transcriptionally distinct cell clusters were identified, which occupied different proportions in healthy and WSSV-infected hemocytes and exerted differential roles in antiviral immune response. Following mapping of the sequencing data to the WSSV genome, we found that all types of hemocytes could be invaded by WSSV virions, especially the cluster 8, which showed the highest transcriptional levels of WSSV genes and exhibited a cell type-specific antiviral response to the viral infection. Further evaluation of the cell clusters revealed the delicate dynamic balance between hemocyte immune response and viral infestation. Unsupervised pseudo-time analysis of hemocytes showed that the hemocytes in immune-resting state could be significantly activated upon WSSV infection and then functionally differentiated to different hemocyte subsets. Collectively, our results revealed the differential responses of shrimp hemocytes and the process of immune-functional differentiation post-WSSV infection, providing essential resource for the systematic insight into the synergistic immune response mechanism against viral infection among hemocyte subtypes.

IMPORTANCE

Current knowledge of shrimp hemocyte classification mainly comes from morphology, which hinder in-depth characterization of cell lineage development, functional differentiation, and different immune response of hemocyte types during pathogenic infections. Here, single-cell RNA sequencing was used for mapping hemocytes during white spot syndrome virus (WSSV) infection in
Litopenaeus vannamei
, identifying 16 cell clusters and evaluating their potential antiviral functional characteristics. We have described the dynamic balance between viral infestation and hemocyte immunity. And the functional differentiation of hemocytes under WSSV stimulation was further characterized. Our results provided a comprehensive transcriptional landscape and revealed the heterogeneous immune response in shrimp hemocytes during WSSV infection.
An obligate microsporidian parasite modulates defense against opportunistic bacterial infection in the yellow fever mosquito
, Aedes aegypti
Authors: El-Dougdoug Noha K. , Magistrado Dom , Short Sarah M. 
Published: February 2024

ABSTRACT

The ability of
Aedes aegypti
mosquitoes to transmit vertebrate pathogens depends on multiple factors, including the mosquitoes’ life history traits, immune response, and microbiota (i.e., the microbes associated with the mosquito throughout its life). The microsporidium
Edhazardia aedis
is an obligate intracellular parasite that specifically infects
Ae. aegypti
mosquitoes and severely affects mosquito survival and other life history traits critical for pathogen transmission. In this work, we investigated how
E. aedis
impacts bacterial infection with
Serratia marcescens
in
Ae. aegypti
mosquitoes. We measured development, survival, and bacterial load in both larval and adult stages of mosquitoes. In larvae,
E. aedis
exposure was either horizontal or vertical and
S. marcescens
was introduced orally. Regardless of the route of transmission,
E. aedis
exposure resulted in significantly higher
S. marcescens
loads in larvae.
E. aedis
exposure also significantly reduced larval survival but subsequent exposure to
S. marcescens
had no effect. In adult females,
E. aedis
exposure was only horizontal and
S. marcescens
was introduced orally or via intrathoracic injection. In both cases,
E. aedis
infection significantly increased
S. marcescens
bacterial loads in adult female mosquitoes. In addition, females infected with
E. aedis
and subsequently injected with
S. marcescens
suffered 100% mortality which corresponded with a rapid increase in bacterial load. These findings suggest that exposure to
E. aedis
can influence the establishment and/or replication of other microbes in the mosquito. This has implications for understanding the ecology of mosquito immune defense and potentially disease transmission by mosquito vector species.

IMPORTANCE

The microsporidium
Edhazardia aedis
is a parasite of the yellow fever mosquito,
Aedes aegypti
. This mosquito transmits multiple viruses to humans in the United States and around the world, including dengue, yellow fever, and Zika viruses. Hundreds of millions of people worldwide will become infected with one of these viruses each year.
E. aedis
infection significantly reduces the lifespan of
Ae. aegypti
and is therefore a promising novel biocontrol agent. Here, we show that when the mosquito is infected with this parasite, it is also significantly more susceptible to infection by an opportunistic bacterial pathogen,
Serratia marcescens
. This novel discovery suggests the mosquito’s ability to control infection by other microbes is impacted by the presence of the parasite.
Effects of low-frequency ultrasound combined with anti-MRSA agents on the mouse model of pulmonary infection
Authors: Yan Kaicheng , Yao Jiahui , Liu Lingling , Liang Wenxin , Cai Yun 
Published: February 2024

ABSTRACT

The treatment of methicillin-resistant
Staphylococcus aureus
(MRSA)-induced pneumonia with antibiotics alone poses considerable challenges. To address these challenges, low-frequency ultrasound (LFU) emerges as a promising approach. In this study, a mouse pneumonia model was established through intratracheal injection of MRSA to investigate the therapeutic efficacy of LFU in combination with antibiotics. Minimal inhibitory concentration was assessed, and the distribution of antibiotics in the lung and plasma was determined using liquid chromatography coupled with mass spectrometry. Various parameters, including the survival rate, histopathology, lung bacterial clearance, and the expressions of cytokines and inflammation-related genes, were evaluated before and after treatment. Compared with the infection group, both the antibiotic-alone groups [vancomycin (VCM), linezolid, and contezolid (CZD)] and the groups in combination with LFU demonstrated an improvement in the survival status of mice. The average colony-forming units of lung tissue in the LFU combination groups were lower compared with the antibiotic-alone groups. While no significant changes in C-reactive protein and procalcitonin in plasma and bronchoalveolar lavage fluid were observed, histopathological results revealed reduced inflammatory damage in LFU combination groups. The secretion of interleukin-6 and tumor necrosis factor-alpha was decreased by the combination treatment, particularly in the VCM + LFU group. Furthermore, the expressions of MRSA virulence factors (
hla
and
agrA
) and inflammation-related genes (
Saa3
,
Cxcl9,
and
Orm1
) were further reduced by the combinations of LFU and antibiotics. Additionally, LFU treatment facilitated the distribution of VCM and CZD in mouse lung tissue at 30 and 45 min, respectively, after dosage.

IMPORTANCE

Treating pneumonia caused by methicillin-resistant
Staphylococcus aureus
(MRSA) with antibiotics alone poses significant challenges. In this
in vivo
study, we present compelling evidence supporting the efficacy of low-frequency ultrasound (LFU) as a promising approach to overcome these obstacles. Our findings demonstrated that LFU enhanced the effectiveness of vancomycin, linezolid, and contezolid in an MRSA pneumonia model. The combination of LFU with anti-MRSA agents markedly improved the survival rate of mice, accelerated the clearance of pulmonary bacteria, reduced inflammatory injury, inhibited the production of MRSA endotoxin, and enhanced the distribution of antibiotics in lung tissue. The application of LFU in the treatment of pulmonary infections held substantial significance. We believe that readers of your journal will find this topic of considerable interest.
Genomic characterization of
Pseudomonas syringae
pv.
syringae
from Callery pear and the efficiency of associated phages in disease protection
Authors: Holtappels D. , Abelson S. A. , Nouth S. C. , Rickus G. E. J. , Amare S. Z. , Giller J. P. , Jian D. Z. , Koskella B. 
Published: February 2024

ABSTRACT

The
Pseudomonas syringae
species complex is a heterogeneous group of plant pathogenic bacteria associated with a wide distribution of plant species. Advances in genomics are revealing the complex evolutionary history of this species complex and the wide array of genetic adaptations underpinning their diverse lifestyles. Here, we genomically characterize two
P. syringae
isolates collected from diseased Callery pears (
Pyrus calleryana
) in Berkeley, California in 2019 and 2022. We also isolated a lytic bacteriophage, which we characterized and evaluated for biocontrol efficiency. Using a multilocus sequence analysis and core genome alignment, we classified the
P. syringae
isolates as members of phylogroup 2, related to other strains previously isolated from
Pyrus
and
Prunus
. An analysis of effector proteins demonstrated an evolutionary conservation of effectoromes across isolates classified in PG2 and yet uncovered unique effector profiles for each, including the two newly identified isolates. Whole-genome sequencing of the associated phage uncovered a novel phage genus related to
Pseudomonas syringae
pv.
actinidiae
phage PHB09 and the
Flaumdravirus
genus. Finally, using
in planta
infection assays, we demonstrate that the phage was equally useful in symptom mitigation of immature pear fruit regardless of the Pss strain tested. Overall, this study demonstrates the diversity of
P. syringae
and their viruses associated with ornamental pear trees, posing spill-over risks to commercial pear trees and the possibility of using phages as biocontrol agents to reduce the impact of disease.

IMPORTANCE

Global change exacerbates the spread and impact of pathogens, especially in agricultural settings. There is a clear need to better monitor the spread and diversity of plant pathogens, including in potential spillover hosts, and for the development of novel and sustainable control strategies. In this study, we characterize the first described strains of
Pseudomonas syringae
pv.
syringae
isolated from Callery pear in Berkeley, California from diseased tissues in an urban environment. We show that these strains have divergent virulence profiles from previously described strains and that they can cause disease in commercial pears. Additionally, we describe a novel bacteriophage that is associated with these strains and explore its potential to act as a biocontrol agent. Together, the data presented here demonstrate that ornamental pear trees harbor novel
P. syringae
pv.
syringae
isolates that potentially pose a risk to local fruit production, or vice versa—but also provide us with novel associated phages, effective in disease mitigation.
Nuclear ribonucleoprotein RALY downregulates foot-and-mouth disease virus replication but antagonized by viral 3C protease
Authors: Wu Jin'en , Sun Chao , Guan Junyong , Abdullah Sahibzada Waheed , Wang Xuefei , Ren Mei , Qiao Lu , Sun Shiqi , Guo Huichen 
Published: February 2024

ABSTRACT

The internal ribosome entry site (IRES) element constitutes a cis-acting RNA regulatory sequence that recruits the ribosomal initiation complex in a cap-independent manner, assisted by various RNA-binding proteins and IRES
trans
-acting factors. Foot-and-mouth disease virus (FMDV) contains a functional IRES element and takes advantage of this element to subvert host translation machinery. Our study identified a novel mechanism wherein RALY, a member of the heterogeneous nuclear ribonucleoproteins (hnRNP) family belonging to RNA-binding proteins, binds to the domain 3 of FMDV IRES via its RNA recognition motif residue. This interaction results in the downregulation of FMDV replication by inhibiting IRES-driven translation. Furthermore, our findings reveal that the inhibitory effect exerted by RALY on FMDV replication is not attributed to the FMDV IRES-mediated assembly of translation initiation complexes but rather to the impediment of 80S ribosome complex formation after binding with 40S ribosomes. Conversely, 3C
pro
of FMDV counteracts RALY-mediated inhibition by the ubiquitin-proteasome pathway. Therefore, these results indicate that RALY, as a novel critical IRES-binding protein, inhibits FMDV replication by blocking the formation of 80S ribosome, providing a deeper understanding of how viruses recruit and manipulate host factors.

IMPORTANCE
The translation of FMDV genomic RNA driven by IRES element is a crucial step for virus infections. Many host proteins are hijacked to regulate FMDV IRES-dependent translation, but the regulatory mechanism remains unknown. Here, we report for the first time that cellular RALY specifically interacts with the IRES of FMDV and negatively regulates viral replication by blocking 80S ribosome assembly on FMDV IRES. Conversely, RALY-mediated inhibition is antagonized by the viral 3C protease by the ubiquitin-proteasome pathway. These results would facilitate further understanding of virus-host interactions and translational control during viral infection.
Duration of Sturtian “Snowball Earth” glaciation linked to exceptionally low mid-ocean ridge outgassing
Authors: Dutkiewicz Adriana , Merdith Andrew S. , Collins Alan S. , Mather Ben , Ilano Lauren , Zahirovic Sabin , Müller R. Dietmar 
Published: February 2024

Abstract
The Sturtian “Snowball Earth” glaciation (ca. 717–661 Ma) is regarded as the most extreme interval of icehouse climate in Earth’s history. The exact trigger and sustention mechanisms for this long-lived global glaciation remain obscure. The most widely debated causes are silicate weathering of the ca. 718 Ma Franklin large igneous province (LIP) and changes in the length and degassing of continental arcs. A new generation of two independent Neoproterozoic full-plate tectonic models now allows us to quantify the role of tectonics in initiating and sustaining the Sturtian glaciation. We find that continental arc length remains relatively constant from 850 Ma until the end of the glaciation in both models and is unlikely to play a role. The two plate motion models diverge in their predictions of the timing and progression of Rodinia break-up, ocean-basin age, ocean-basement depth, sea-level evolution, and mid-ocean ridge (MOR) carbon outflux. One model predicts MOR outflux and ocean basin volume–driven sea level lower than during the Late Cenozoic glaciation, while the other predicts outgassing and sea level exceeding those of the Late Cretaceous hothouse climate. The second model would preclude a major glaciation, while the first model implies that the trigger for the Sturtian glaciation could have been a combination of an extremely low MOR outflux (~9 Mt C/yr) and Franklin LIP weathering. Such minimal outflux could have maintained an icehouse state for 57 m.y. when silicate weathering was markedly reduced, with a gradual build-up of MOR CO2 in the atmosphere paired with terrestrial volcanism leading to its termination.
Impact of the COVID-19 pandemic on the clinical management trends for acute appendicitis among the under-25s: a retrospective study
Authors: Faitna Puji , Harwood Rachel , Kenny Simon E , Viner Russell M , Aylin Paul P , Hargreaves Dougal S , Bottle Alex 
Published: February 2024

ObjectiveTo describe the COVID-19 pandemic’s impact on acute appendicitis management on children and young people (CYP).DesignRetrospective cohort study.SettingAll English National Health Service hospitals.PatientsAcute appendicitis admissions (all, simple, complex) by CYP (under-5s, 5–9s, 10–24s).ExposureStudy pandemic period: February 2020–March 2021. Comparator pre-pandemic period: February 2015–January 2020.Main outcome measuresMonthly appendicectomy and laparoscopic appendicectomy rate trends and absolute differences between pandemic month and the pre-pandemic average. Proportions of appendicitis admissions comprising complex appendicitis by hospital with or without specialist paediatric centres were compared.Results101 462 acute appendicitis admissions were analysed. Appendicectomy rates fell most in April 2020 for the 5–9s (−18.4% (95% CI −26.8% to −10.0%)) and 10–24s (−28.4% (−38.9% to −18.0%)), driven by reductions in appendicectomies for simple appendicitis. This was equivalent to −54 procedures (−68.4 to −39.6) and −512 (−555.9 to −467.3) for the 5–9s and 10–24s, respectively. Laparoscopic appendicectomies fell in April 2020 for the 5–9s (−15.5% (−23.2% to −7.8%)) and 10–24s (−44.8% (−57.9% to −31.6%) across all types, which was equivalent to −43 (−56.1 to 30.3) and −643 (−692.5 to −593.1) procedures for the 5–9s and 10–24s, respectively. A larger proportion of complex appendicitis admissions were treated within trusts with specialist paediatric centres during the pandemic.ConclusionsFor CYP across English hospitals, a sharp recovery followed a steep reduction in appendicectomy rates in April 2020, due to concerns with COVID-19 transmission. This builds on smaller-sized studies reporting the immediate short-term impacts.
Using the providers’ perspective on video review of neonatal procedures to create a roadmap: a qualitative study
Authors: Heesters Veerle , van Zanten Henriëtte A , den Boer Maria C , te Pas Arjan B , Witlox Ruben SGM 
Published: February 2024

ObjectiveTo examine the providers’ perceptions and experiences on implementation of video review (VR) of procedures in the neonatal intensive care unit (NICU).DesignQualitative study using semi-structured interviews with neonatal care providers about their experiences with VR. Interviews were audio-recorded, transcribed and thematically analysed using the data analysis software Atlas.ti V.22.2.SettingProviders working in the NICU of the Leiden University Medical Center were interviewed during implementation of VR.ResultsIn total, 28 NICU staff members were interviewed. The interviewed providers appreciated VR and valued the focus on a safe learning environment. Five overarching themes were identified: (1) added value: providers reported that VR is a powerful tool for reflection on daily practice and serves as a magnifying glass on practice, provides a helicopter view and VR with nursing and medical staff together led to new insights and was seen as highly valuable; (2) preconditions and considerations: the existing culture of trust on the NICU positively influenced providers’ perception; (3) adjustment: it was recommended to first let providers attend a VR session, before being recorded; (4) experiences with VR: suggestions were made by the providers regarding the preparation and organisation of VR and the role of the chair; (5) embedding VR: providers considered how to embed VR on the long-term while maintaining a safe learning environment and provided suggestions for expanding.ConclusionNeonatal care providers appreciated the use of VR and provided viewpoints on how to implement VR successfully, which were used to develop a roadmap with recommendations.
Transnasal endoscopic drainage of neonatal orbital abscess
Authors: Balaraj Soujanya , Sridhar Aishwarya , Sajith Milu , Channegowda Chandrakiran 
Published: February 2024

Neonatal orbital complications are rare and potentially fatal, demanding prompt diagnosis and adequate treatment. A 25-day-old neonate presented with rapidly progressive orbital complications as evidenced by proptosis, chemosis, lid oedema and restricted eye movements, developing within 3 days. There was no significant medical history or risk factors for developing infection. An initial conservative approach with antimicrobial therapy failed to show any resolve. An MRI brain, orbits and paranasal sinuses demonstrated that there were features suggestive of right orbital cellulitis with possibility of abscess formation with right ethmoidal mucoinflammatory disease and mass effect on the optic nerve causing stretching and compression by the surrounding inflammation.The patient was treated successfully with transnasal endoscopic drainage and decompression. Endoscopic access was challenging owing to the restrictive anatomy. Postoperatively, the patient showed improvement, with gradual decrease in proptosis and resolve in eye movements.