bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pseudorabies virus UL13 protein kinase triggers phosphorylation of the RNA demethylase FTO, which is associated with FTO-dependent suppression of interferon-stimulated gene expression
Authors: Verhamme Ruth , Jansens Robert J. J. , Liu Jianheng , Van Raemdonck Fien , Van Waesberghe Cliff , Nicholson Luke , Jaffrey Samie R. , Favoreel Herman W. 
Published: January 2025

ABSTRACT

Alpha-ketoglutarate-dependent dioxygenase, also known as fat mass and obesity-associated protein (FTO), is an RNA demethylase that mediates the demethylation of N
6
,2-O-dimethyladenosine (m6Am) and N
6
-methyladenosine (m6A). Both m6Am and m6A are prevalent modifications in mRNA and affect different aspects of transcript biology, including splicing, nuclear export, translation efficiency, and degradation. The role of FTO during (herpes) virus infection remains largely unexplored. In this study, we show that the UL13 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) triggers phosphorylation of FTO. In primary epithelial cells, depletion of FTO leads to increased expression of antiviral interferon-stimulated genes (ISGs) and UL13 triggers FTO-dependent suppression of ISG expression. Although PRV infection suppresses m6Am levels in host small nuclear RNA, this is independent of UL13. The current data highlight FTO as an important regulator of antiviral ISG expression and suggest that UL13-mediated phosphorylation of FTO may serve as a previously unrecognized viral strategy to suppress the antiviral interferon response.

IMPORTANCE
RNA modification pathways play important roles in diverse cellular processes and virus life cycles. Although previous studies have demonstrated that alphaherpesviruses can substantially influence cellular RNA modifications, such as m6A, the impact on the m6Am epitranscriptome machinery remains largely unexplored. The present work reports that the UL13 protein kinase of pseudorabies virus (PRV), an alphaherpesvirus, mediates phosphorylation of the m6Am/m6A eraser FTO and that this correlates with a UL13- and FTO-dependent suppression of antiviral interferon-stimulated gene (ISG) expression. Furthermore, PRV infection leads to a pronounced reduction in m6Am levels in host snRNA and also induces phosphorylation of the m6Am writer PCIF1. These data highlight FTO as an important regulator of ISG expression and reveal that viral manipulation of FTO, such as UL13-induced phosphorylation of FTO, may serve as a previously unrecognized interferon evasion strategy.
Sixty-five draft genome sequences of
Campylobacter coli
and
Campylobacter jejuni
from table egg layer chickens
Authors: Meinersmann Richard J. , Robinson-McKenzie Tanisha S. , Garcia Javier S. , Jones Deana R. 
Published: January 2025

ABSTRACT

We present the draft genomic sequences of 65 isolates of
Campylobacter
spp. (38
Campylobacter coli
and 27
Campylobacter jejuni
) isolated from table egg-layer chickens, which are not generally associated with human transmission. Up to this time, there are no publicly available genomic sequences of
Campylobacter
isolated from laying hens.
Complete genome sequence of
Staphylococcus epidermidis
B273 and its epidermicin NI01 biosynthesis plasmid
Authors: Nicholas-Haizelden Keir , Chong Charlotte E. , Alqahtani Norah , Alsaadi Samah E. , Horsburgh Malcolm J. 
Published: January 2025

ABSTRACT

The human skin commensal
Staphylococcus epidermidis
produces diverse, therapeutically relevant bacteriocins. We report the complete whole-genome sequence of the nasal isolate
S. epidermidis
B273, which contains a plasmid with the biosynthetic gene cluster for epidermicin NI01, a broad-spectrum type II antimicrobial peptide.
Inhibition of Unc-51-like-kinase is mitoprotective during
Pseudomonas aeruginosa
infection in corneal epithelial cells
Authors: Ayilam Ramachandran Rajalakshmy , Titone Rossella , Abdallah Joelle T. , Rehman Mahad , Cao Mou , Baniasadi Hamid , Robertson Danielle M. 
Published: January 2025

ABSTRACT

Pseudomonas aeruginosa
(PA) is an opportunistic gram-negative pathogen that can infect the cornea, leading to permanent vision loss. Autophagy is a cannibalistic process that drives cytoplasmic components to the lysosome for degradation and/or recycling. Autophagy has been shown to play a key role in the removal of intracellular pathogens and, as such, is an important component of the innate immune response. Autophagy is intimately linked to mitochondria, organelles that mediate energy homeostasis, immune signaling, and cell death. Using a combination of biochemical and imaging approaches, we investigated the effects of PA on autophagy and host cell mitochondria in relation to pro-inflammatory cytokine expression. Using a standard invasive test strain of PA, we show that PA infection triggers dephosphorylation of the mechanistic target of rapamycin in corneal epithelial cells, leading to the induction of autophagy through ULK1/2. This was associated with robust mitochondrial depolarization, changes in mitochondrial ultrastructure, and an increase in IL-6 and IL-8 secretion. PA infection was also associated with an increase in purine metabolism by host cells. Treatment with the ULK1/2 inhibitor, MRT68921, which blocks phagophore formation, attenuated levels of intracellular PA in corneal epithelial cells. Unexpectedly, treatment of cells with MRT68921 blocked PA-induced mitochondrial depolarization and downregulated purine and pyrimidine metabolism. While MRT68921 attenuated the PA-induced increase in IL-6, it further increased IL-8 and neutrophil chemotaxis. This was associated with the nuclear internalization of NF
κ
B. Taken together, these findings highlight a novel mechanism whereby the inhibition of ULK1/2 activity confers mitoprotection during PA infection in corneal epithelial cells.

IMPORTANCE

Pseudomonas aeruginosa
(PA) is a common pathogen that can cause severe disease in man. In the eye, PA infection can lead to blindness. In this study, we show that PA induces autophagy, a mechanism whereby cells recycle damaged proteins and organelles. PA infection further depolarizes mitochondria, leading to the release of pro-inflammatory mediators. Unexpectedly, the inhibition of ULK1/2, an enzyme involved in the early stages of autophagy, not only inhibits autophagy but enhances mitochondrial polarization. This leads to a reduction in intracellular levels of PA and changes in the inflammatory milieu. Together, these data suggest that the inhibition of ULK1/2 may be mitoprotective in corneal epithelial cells during PA infection.
Histological staining of tick bite skin biopsies for spirochetes and Powassan virus RNA
Authors: Oufattole Jihane , Piantadosi Anne , Telford Sam R. , Laga Alvaro C. , Solomon Isaac H. 
Published: January 2025

ABSTRACT

Ixodes scapularis
is a vector of several human pathogens in the United States, including
Borrelia burgdorferi,
the cause of Lyme disease, and Powassan virus (POWV), an emerging cause of severe encephalitis. Skin biopsies from tick bite sites are frequently collected and tested for the presence of spirochetes (
Borrelia
spp.), which remain elusive. POWV testing is not performed despite the increasing incidence of POWV encephalitis. To determine the utility of staining skin biopsies for tick-borne pathogens, formalin-fixed paraffin-embedded specimens from 2010 to 2023 were examined by hematoxylin and eosin, Warthin–Starry stain, spirochete immunohistochemistry, and POWV
in situ
hybridization (ISH). These assays were optimized by staining histological sections from whole ticks, from which spirochetes were detected in two out of 14 patient-derived specimens, and POWV RNA was detected in multiple experimentally infected ticks. None of the 36 skin biopsies were positive for spirochetes, including 20 with retained tick mouth parts and six from patients with positive Lyme serology. POWV ISH was negative in all biopsies, including one laboratory confirmed case. Combining patients with skin biopsies and whole ticks (
n
= 50), spirochetes were detected in specimens from only 1/5 (20%) patients with suspected erythema chronicum migrans (ECM). Although limited, our data suggest a poor correlation between ECM and the detection of spirochetes, findings in concordance with the published literature. Similarly, the absence of detectable POWV RNA in any of the tested skin biopsies or patient-derived ticks, including one laboratory confirmed case, suggest the limited utility of POWV ISH for clinical use without further analysis with a larger sample size.

IMPORTANCE

Tick-borne infections, including Lyme and Powassan encephalitis, cause significant morbidity and mortality and are challenging to diagnose and study in humans. We examined skin biopsies from patients with tick bites to look for direct evidence of microbes by histochemical, immunohistochemical, and
in situ
hybridization stains. To validate these assays, we also tested the same stains on histological sections from whole ticks infected with spirochetes or Powassan virus. Examination of skin biopsies using similar tools may prove valuable in studying the pathogenesis of diseases, such as southern tick-associated rash illness, for which a causative pathogen has not yet been identified.
Emerging carbapenem-resistant
Klebsiella pneumoniae
in a tertiary care hospital in Lima, Peru
Authors: Krapp Fiorella , Cuicapuza Diego , Salvatierra Guillermo , Buteau Jean P. , Amaro Catherine , Astocondor Lizeth , Hinostroza Noemí , Jacobs Jan , García Coralith , Tsukayama Pablo 
Published: January 2025

ABSTRACT

The emergence of carbapenem-resistant
Klebsiella pneumoniae
(CRKP) poses a significant public health threat, particularly in low- and middle-income countries (LMICs) with limited surveillance and treatment options. This study examines the genetic diversity, resistance patterns, and transmission dynamics of 66 CRKP isolates recovered over 5 years (2015–2019) after the first case of CRKP was identified at a tertiary care hospital in Lima, Peru. Our findings reveal a shift from
bla
KPC-2
to
bla
NDM-1
as the dominant carbapenemase gene after 2017. Lineage ST45 was the most prevalent and persisted for multiple years, followed by high-risk clones ST11 and ST147. The
bla
NDM-1
gene was carried almost exclusively by a Tn125-like transposon, similar to the one reported in previous studies from two Peruvian hospitals. Long-read sequencing revealed nearly identical
bla
NDM
-carrying plasmids across the four assessed lineages. A comparative analysis of 1,023 South American CRKP genomes confirmed a unique pattern in Peru, where
bla
NDM-1
(81.4%) outpaced
bla
KPC-2
, which remained dominant (59.4%) elsewhere. In addition, emerging clones ST45 and ST348 found in Peru were rarely found elsewhere in South America, suggesting potential regional adaptation. In conclusion, our study provides a comprehensive picture of the intra-hospital dynamics of these emerging pathogens and provides a framework for studying their genomic diversity in the understudied South American region.

IMPORTANCE

This study provides novel insights into the transmission and genetic diversity of carbapenem-resistant
Klebsiella pneumoniae
, a bacteria responsible for severe infections, with limited treatment options. By examining isolates recovered over 5 years at a major hospital in Lima, Peru, we demonstrated a shift from one type of resistance gene,
bla
KPC
, to another,
bla
NDM
, which is more challenging to treat. Our findings reveal that specific bacterial lineages carrying the
bla
NDM
gene in a specific plasmid are emerging in Peru, including well-known high-risk strains and others rarely found elsewhere in South America. This pattern highlights an urgent need for targeted surveillance and infection control as these strains pose a significant challenge to healthcare systems. Our study provides crucial data on
Klebsiella pneumoniae
in Peru, contributing to broader efforts to monitor and control antibiotic-resistant infections in South America and globally.
Using routine primary care data in research: (in)efficient case studies and perspectives from the Asthma UK Centre for Applied Research
Authors: Tibble Holly , Alyami Rami A , Bush Andrew , Cunningham Steve , Julious Steven , Price David , Quint Jennifer K , Turner Stephen , Wang Kay , Wilson Andrew , Davies Gwyneth A , Mukherjee Mome , Chan Amy Hai Yan , Varghese Deepa , Jackson Tracy , Morgan Noelle , Daines Luke , Pinnock Hilary 
Published: January 2025

AimWe aimed to identify enablers and barriers of using primary care routine data for healthcare research, to formulate recommendations for improving efficiency in knowledge discovery.BackgroundData recorded routinely in primary care can be used for estimating the impact of interventions provided within routine care for all people who are clinically eligible. Despite official promotion of ‘efficient trial designs’, anecdotally researchers in the Asthma UK Centre for Applied Research (AUKCAR) have encountered multiple barriers to accessing and using routine data.MethodsUsing studies within the AUKCAR portfolio as exemplars, we captured limitations, barriers, successes, and strengths through correspondence and discussions with the principal investigators and project managers of the case studies.ResultsWe identified 14 studies (8 trials, 2 developmental studies and 4 observational studies). Investigators agreed that using routine primary care data potentially offered a convenient collection of data for effectiveness outcomes, health economic assessment and process evaluation in one data extraction. However, this advantage was overshadowed by time-consuming processes that were major barriers to conducting efficient research. Common themes were multiple layers of information governance approvals in addition to the ethics and local governance approvals required by all health service research; lack of standardisation so that local approvals required diverse paperwork and reached conflicting conclusions as to whether a study should be approved. Practical consequences included a trial that over-recruited by 20% in order to randomise 144 practices with all required permissions, and a 5-year delay in reporting a trial while retrospectively applied regulations were satisfied to allow data linkage.ConclusionsOvercoming the substantial barriers of using routine primary care data will require a streamlined governance process, standardised understanding/application of regulations and adequate National Health Service IT (Information Technology) capability. Without policy-driven prioritisation of these changes, the potential of this valuable resource will not be leveraged.
Diffusion tensor imaging in peroneal neuropathy: a prospective, single-centre study
Authors: Oosterbos Christophe , Radwan Ahmed M , Sunaert Stefan , Hoornaert Sophie , Van Hoylandt Anais , Lemmens Robin , Theys Tom 
Published: January 2025

ObjectiveDiffusion tensor imaging (DTI) showed promising results in diagnosing upper limb neuropathies, but its value in patients with foot drop due to peroneal neuropathy has not yet been investigated. We aim to establish reference values for DTI metrics of the healthy peroneal nerve and to evaluate differences in DTI metrics between patients and healthy controls.MethodsDiffusion-weighted images (DWI) from 22 pathological nerves, 14 asymptomatic patients’ nerves and 65 healthy peroneal nerves were processed for quantitative assessment of fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity and mean diffusivity. Clinical baseline and follow-up data were prospectively collected for all patients.ResultsMean patient FA values (0.40, SD 0.08) were significantly lower compared with healthy controls (mean FA 0.44, SD 0.06). Mean patient RD values (0.98 10−3mm2/s, SD 0.21 10−3mm2/s) were significantly higher compared with healthy controls (mean RD 0.85 10−3mm2/s, SD 0.16 10−3mm2/s). FA values were significantly lower in patients with severe foot drop (mean FA 0.40, SD 0.06) compared with non-severe foot drop (mean FA 0.48, SD 0.05).ConclusionBased on these results, DTI appears to aid in the differential diagnostic process of patients with peroneal neuropathy. Future studies should focus on automation of DWI processing, confirm the results in larger patient groups and try to establish reliable cut-off values for DTI metrics.
Factors influencing COVID-19 vaccine acceptability among household heads in northern Nigeria: a community-based cross-sectional study
Authors: Ahmad Suleiman Idris , Aliyu Hafiz , Usman Rabi , Abubakar Ahmed , Maijawa Muhammad Abdullahi , Suleiman Bello Abdullahi , Balogun Muhammad Shakir , Olorukooba Abdulhakeem , Umeokonkwo Chukwuma David , Maiyaki Abubakar , Abubakar Muhammadu Sani , Abba Aisha Abdulazeez , Yisa Mohammed , Zubair Ismail , Onu Chinedu Hastings , Jatau Tenmuso David , Garba Fatima , Kabir Sabitu 
Published: January 2025

ObjectivesCOVID-19 vaccine was rolled out for the public in August 2021 in Zamfara state, Northen Nigeria. We determined the factors influencing COVID-19 vaccine acceptance.SettingsWe executed a community-based analytical cross-sectional study during the first 4 months of the second phase of the COVID-19 (Oxford/AstraZeneca) mass vaccination campaign in Zamfara state.ParticipantsWe used multistage sampling to select 910 household heads.Outcome measuresWe used a semistructured electronic questionnaire to collect data on sociodemographic characteristics, uptake and acceptance of COVID-19 vaccine between 12 October and 20 December 2021. We calculated frequencies, proportions, adjusted ORs and 95% CIs for factors influencing COVID-19 vaccine acceptance using logistic regression.ResultsOur respondents had a median age of 48 years (IQR: 37–55), 78.1% (711) were men, a majority more than 30 years, and only 8.9% (81) had received COVID-19 vaccine. Of the 829 unvaccinated respondents, 10.1% (84) accepted to take the vaccine, the current week of the interview while 12.2% (101) rejected the vaccine. Individuals aged 30 years and older (adjusted OR (aOR)=2.39, 95% CI 1.16 to 4.94, p=0.018), who owned a mobile phone (aOR=25.35, 95% CI 11.23 to 57.23, p<0.001) and a television (aOR=3.72, 95% CI 1.09 to 12.69, p=0.036), with medium–high levels of trust (aOR=7.41, 95% CI 3.10 to 17.74, p<0.001), and those with a medium–high (positive) levels of attitude (aOR=1.82, 95% CI 1.06 to 3.11, p=0.029) were more likely to accept the COVID-19 vaccine. Also, those who had been vaccinated with other vaccines (aOR=2.2, 95% CI 1.09 to 4.43, p=0.027) and those previously tested for COVID-19 (aOR=2.0, 95% CI 1.10 to 3.66, p=0.023) were also more likely to accept it.ConclusionCOVID-19 vaccine had a poor uptake and acceptance. Factors such as age, awareness, trust and previous vaccination experience played a significant role in COVID-19 vaccine acceptance. We recommended targeted public health campaigns, improving community engagement and building trust in community leaders, healthcare providers and public health institutions.
Effects of interventions aimed at improving nurses’ work engagement in the workplace: a systematic review and meta-analysis protocol
Authors: Kuribayashi Kazuto , Inagaki Akiko , Imamura Kotaro , Kawakami Norito 
Published: January 2025

IntroductionWork engagement enhances nurses’ physical and mental health, well-being, job performance and satisfaction. This reduces turnover rates and improves patient care quality, making work engagement a crucial factor in the nursing workplace. However, no systematic review or meta-analysis has explored the effects of randomised controlled trial (RCT) interventions aimed at improving nurses’ work engagement. This study aimed to evaluate the effectiveness of these interventions, providing healthcare organisations with evidence-based recommendations for enhancing work engagement among nurses.Methods and analysisThis systematic review and meta-analysis will use the PICO criteria: (P) nurses, (I) psychosocial interventions, (C) no intervention or non-work engagement interventions and (O) work engagement as a primary outcome. Published studies will be searched by September 2025 using databases such as the Cochrane Central Register of Controlled Trials, PubMed (MEDLINE), Embase, CINAHL, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies must use RCT designs, assess the impact of interventions on nurses’ work engagement and provide adequate data (sample sizes, means and SDs) to calculate effect sizes with 95% CIs. Publications must be written in English or Japanese as original articles. Two reviewers will independently select studies and assess the risk of bias. The methodological quality of the included studies will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation approach. A meta-analysis will be conducted for statistical synthesis and publication bias will be assessed using Egger’s test and a visual funnel plot. Heterogeneity will be evaluated using Q statistics.Ethics and disseminationThis systematic review and meta-analysis are based on existing studies and do not require ethical approval. The findings will be shared through publications in peer-reviewed international journals and presentations at relevant conferences, symposia and seminars.PROSPERO registration numberCRD42024510479.
Characteristics of suicide prevention apps: a content analysis of apps available in Canada and the UK
Authors: Bennett-Poynter Laura , Groves Samantha , Kemp Jessica , Shin Hwayeon Danielle , Sequeira Lydia , Lascelles Karen , Strudwick Gillian 
Published: January 2025

ObjectivesWe aimed to examine the characteristics, features and content of suicide prevention mobile apps available in app stores in Canada and the UK.DesignSuicide prevention apps were identified from Apple and Android app stores between March and April 2023. Apps were screened against predefined inclusion criteria, and duplicate apps were removed. Data were then extracted based on descriptive (eg, genre, app developer), security (eg, password protection) and design features (eg, personalisation options). Content of apps was assessed using the Essential Features Framework. Extracted data were analysed using a content analysis approach including narrative frequencies and descriptive statistics.Data sourcesApple and Android app stores between March and April 2023.Eligibility criteriaIdentified apps were eligible for inclusion if they were: (a) free, (b) developed in the English language, (c) could be downloaded on an Apple or Android device in England or Canada, (d) the focus of the app was suicide prevention and (e) the target users of the app were individuals experiencing suicide-related thoughts and/or behaviours.Data extraction and synthesisApps were assessed on basic descriptive data (eg, name, genre, developer of the app), alongside security (eg, whether password protection was available) and design features (eg, whether the app could be personalised). App content was examined using the Essential Features Framework.Results52 suicide prevention apps were included within the review. Most were tailored for the general population and were in English language only. One app had the option to increase app accessibility by offering content presented using sign language. Many apps allowed some form of personalisation by adding text content, however most did not facilitate further customisation such as the ability to upload photo and audio content. All identified apps included content from at least one of the domains of the Essential Features Framework. The most commonly included domains were sources of suicide prevention support, and information about suicide. The domain least frequently included was screening tools followed by wellness content. No identified apps had the ability to be linked to patient medical records.ConclusionsThe findings of this research present implications for the development of future suicide prevention apps. Development of a co-produced suicide prevention app which is accessible, allows for personalisation and can be integrated into clinical care may present an opportunity to enhance suicide prevention support for individuals experiencing suicidal thoughts and behaviours.