bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli
Authors: Han Yuhong , Zhou Mengmeng , Wang Bing , Jiang Jin
Published: January 2025

Hedgehog (Hh) morphogen governs embryonic development and tissue homeostasis through the Ci/Gli family transcription factors. Here we report that Hh induces phase separation of the fused (Fu)/Ulk family kinases to allosterically regulate Ci/Gli. We find that Hh-induced phosphorylation of Fu/Ulk3 promotes SUMOylation of their inverted phosphorylation-dependent SUMOylation motifs. Subsequent interaction between SUMO and SUMO-interacting motif drives Fu/Ulk3 self-assembly to form biomolecular condensates that recruit Ci-Sufu and Gli-Sufu in the cytoplasm and primary cilium, respectively. Within the condensates, Fu/Ulk3 undergoes a conformational change to expose Ci/Gli for Fu/Ulk3-mediated phosphorylation and activation, leading to gradual accumulation of nuclear Ci
A
/Gli
A
transcriptional complexes in proportion to ligand dose and exposure time. Our findings provide mechanistic insights into the spatiotemporal control of Hh signal transduction, reveal previously unexplored regulatory mechanism and function for biomolecular condensation, and establish a paradigm for kinase-mediated signal transduction whereby a kinase allosterically activates its substrate through ligand-induced and condensation-driven conformational change.
2′-Fucosyllactose inhibits human norovirus replication in human intestinal enteroids
Authors: Patil Ketki , Ayyar B. Vijayalakshmi , Hayes Nicole M. , Neill Frederick H. , Bode Lars , Estes Mary K. , Atmar Robert L. , Ramani Sasirekha
Published: January 2025

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2′-fucosyllactose (2′FL) in the same pocket as HBGAs for some HuNoV strains. We evaluated the effect of 2′FL on the replication of a globally dominant GII.4 Sydney [P16] HuNoV strain using human intestinal enteroids (HIEs) from adults and children. A significant reduction in GII.4 Sydney [P16] replication was seen in duodenal and jejunal HIEs from multiple adult donors, all segments of the small intestine from an adult organ donor, and in two pediatric duodenal HIEs. However, 2′FL did not inhibit HuNoV replication in two infant jejunal HIEs that had significantly lower expression of α1–2-fucosylated glycans. 2′FL can be synthesized in large scale, and safety and tolerance have been assessed previously. Our data suggest that 2′FL has the potential to be developed as a therapeutic for HuNoV gastroenteritis.

IMPORTANCE

Human noroviruses infect the gastrointestinal tract and are a leading cause of acute gastroenteritis worldwide. Common symptoms of norovirus include diarrhea, vomiting, and stomach cramps. Virus shedding and symptoms are prolonged and debilitating in immunocompromised patients. Currently, there are no approved vaccines or targeted antivirals for treating human norovirus infection. Human intestinal enteroids derived from intestinal stem cells allow the successful replication of norovirus in the laboratory and can be used as a physiologically relevant model system to evaluate antivirals. We discovered that 2′-fucosyllactose (2′FL), an oligosaccharide naturally occurring in human milk, inhibits GII.4 norovirus replication in HIEs from multiple donors and thus has the potential to be developed as a therapeutic for human norovirus. These findings have high translational potential since 2′FL from several manufacturers has a “generally recognized as safe” status and can be synthesized on a large scale for immediate application.
Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia
Authors: Hippee Camilla E. , Durnell Lorellin A. , Kaufman Justin W. , Murray Eileen , Singh Brajesh K. , Sinn Patrick L.
Published: January 2025

Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell. We previously described the phenomenon in which infectious centers detach
en masse
from HAE and remain viable. Here, we investigate the mechanism of this cellular detachment. Via immunostaining, we observed loss of tight junction and cell adhesion proteins within infectious centers. These morphological changes indicate activation of epithelial-to-mesenchymal transition (EMT). EMT can contribute to wound healing in respiratory epithelia by mobilizing nearby cells. Inhibiting TGF-β, and thus EMT, reduced infectious center detachment. Compared with uninfected cells, MeV-infected cells also expressed increased levels of sphingosine kinase 1 (SK1), a regulator of live cell extrusion. Live cell extrusion encourages cells to detach from respiratory epithelia by contracting the actomyosin of neighboring cells. Inhibition or induction of live cell extrusion impacted infectious center detachment rates. Thus, these two related pathways contributed to infectious center detachment in HAE. Detached infectious centers contained high titers of virus that may be protected from the environment, allowing the virus to live on surfaces longer and infect more hosts.

IMPORTANCE

Measles virus (MeV) is an extremely contagious respiratory pathogen that continues to cause large, disruptive outbreaks each year. Here, we examine mechanisms of detachment of MeV-infected cells. MeV spreads cell-to-cell in human airway epithelial cells (HAE) to form groups of infected cells, termed “infectious centers”. We reported that infectious centers ultimately detach from HAE as a unit, carrying high titers of virus. Viral particles within cells may be more protected from environmental conditions, such as ultraviolet radiation and desiccation. We identified two host pathways, epithelial-to-mesenchymal transition and live cell extrusion, that contribute to infectious center detachment. Perturbing these pathways altered the kinetics of infectious center detachment. These pathways influence one another and contribute to epithelial wound healing, suggesting that infectious center detachment may be a usurped consequence of the host’s response to infection that benefits MeV by increasing its transmissibility between hosts.
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

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

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

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

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

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

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.
Littréhernia: strangulated Meckel’s diverticulum requiring small intestine resection
Authors: Yu Joyce , Ip Julian
Published: January 2025

Littré hernia is the rare protrusion of a Meckel’s diverticulum (MD) through a hernia sac. We present a rare case of strangulated MD in a woman patient in her 90s, which required a small intestine resection. She presented with 1 day of groin swelling, no features of bowel obstruction and an irreducible hernia on examination. On CT, there were radiological features of strangulation, and the patient was taken for an emergency operation. Findings included a femoral hernia containing strangulated MD with clinical features of ischaemic small bowel. The affected segment was resected, and a side-to-side anastomosis was performed. She recovered well postoperatively. This report emphasises that the clinical diagnosis of Littré hernia can be insidious, and the importance of imaging to aid decision-making.
Renal vessel pseudoaneurysm as a cause of recurrent haematuria
Authors: Kumar Prem , Kumar Prashant , Singh Rana Pratap , Prem Pragya
Published: January 2025

Pseudoaneurysm is a common vascular abnormality marked by arterial wall disruption, with complications that can arise unpredictably and carry high morbidity and mortality rates. This case study emphasises the management of recurrent haematuria and clot retention in a young man presenting to the emergency department. It underscores the importance of early recognition and management of recurrent haematuria and clot retention caused by pseudoaneurysm, emphasising the critical role of multidisciplinary collaboration in optimising patient outcomes.
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

Aim

We aimed to identify enablers and barriers of using primary care routine data for healthcare research, to formulate recommendations for improving efficiency in knowledge discovery.

Background

Data 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.

Methods

Using 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.

Results

We 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.

Conclusions

Overcoming 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

Objective

Diffusion 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.

Methods

Diffusion-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.

Results

Mean 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).

Conclusion

Based 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

Objectives

COVID-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.

Settings

We 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.

Participants

We used multistage sampling to select 910 household heads.

Outcome measures

We 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.

Results

Our 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.

Conclusion

COVID-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

Introduction

Work 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 analysis

This 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 dissemination

This 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 number

CRD42024510479.
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

Objectives

We aimed to examine the characteristics, features and content of suicide prevention mobile apps available in app stores in Canada and the UK.

Design

Suicide 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 sources

Apple and Android app stores between March and April 2023.

Eligibility criteria

Identified 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 synthesis

Apps 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.

Results

52 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.

Conclusions

The 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.
Powerful together with diabetes, a group-based self-management intervention for patients with type 2 diabetes from lower educational groups: study protocol for a hybrid type 2 evaluation
Authors: Horreh Bedra , van Nassau Femke , Landais Lorraine , Vissenberg Charlotte , van Dongen Johanna M , van der Ploeg Hidde P , Stronks Karien
Published: January 2025

Introduction

Type 2 diabetes mellitus (T2DM) is a major burden on public health worldwide. To reduce adverse events and complications, effective T2DM self-management is required. Self-management and glycaemic control are generally poorer in lower educated people compared with higher educated people. This study aims to assess the (cost-)effectiveness and to conduct a process evaluation of a diabetes self-management programme, ‘Powerful Together With Diabetes’ (PTWD), which is specifically developed for patients from lower educational groups.

Methods and analysis

The PTWD programme is focused on attaining basic knowledge and skills for effective diabetes self-management. In a previous study (the Diabetes in Social Context (DISC) study), lower-educated participants enjoyed the PTWD programme as well as improved their T2DM-related behaviours. The design of the study is an effectiveness-implementation hybrid type 2 trial. We will conduct mixed methods effectiveness, process and economic evaluations. To investigate the (cost-)effectiveness, a two-arm quasi-experimental trial will be conducted with a parallel mixed method process evaluation. The primary outcome of the study is change in haemoglobin A1c levels from baseline to 12 months. Secondary outcomes include use of primary and secondary care, medication use, blood biomarkers, T2DM self-management health behaviours, anthropometrics, and quality of life. Data will be collected with questionnaires, physical activity trackers and registration data from general practitioner registries. To see if the results are maintained, we will also measure the outcomes 24 months after baseline. Study participants are patients from lower educational groups living with T2DM between 35 and 70 years old. Participants will be recruited through general practices, and the intervention will be held in community centres. Our aim is to include 114 participants in the intervention group and 570 participants in the control group.

Ethics and dissemination

This study has been approved by the Medical Ethics Committee of the Academic Medical Center in Amsterdam (#2021_222). Participants will sign an informed consent form prior to enrolment. Manuscripts with the results of the effectiveness, economic and process evaluations will be published in peer-reviewed journals.

Trial registration number

ISRCTN12982302ISRCTN registry (registered on 29 March 2022).
Calculating the Hawking temperature of black holes in f(Q) gravity using the RVB method: a residue-based approach
Authors: Chen Wen-Xiang
Published: January 2025

This paper explores the computation of Hawking temperatures for black holes within various f( Q) gravity models using the RVB (Robson–Villari–Biancalana) method. This topological approach reveals an additional term in the temperature calculation, which we propose is a residue arising from the contour integral [Formula: see text], where f( z) represents a function related to the black hole’s metric or curvature. By analyzing several specific f( Q) models including f( Q) = Q + α Q2, f( Q) = Q + βln ( Q), [Formula: see text], f( Q) = Q n as well as the Reissner–Nordstrm, Kerr, and Kerr–Newman black holes, we demonstrate that the correction term C can be consistently interpreted as this residue, providing new insights into black hole thermodynamics in modified gravity frameworks. We also expand on important physical aspects such as black hole stability, late-stage evaporation, extremality bounds in charged and rotating spacetimes, and potential novel phases emerging from different forms of f( Q).
Minimal Neural Network Conditions for Encoding Future Interactions
Authors: Diez-Hermano Sergio , Aparicio-Rodriguez Gonzalo , Manubens Paloma , Sanchez-Jimenez Abel , Calvo-Tapia Carlos , Levcik David , Villacorta-Atienza José Antonio
Published: January 2025

Space and time are fundamental attributes of the external world. Deciphering the brain mechanisms involved in processing the surrounding environment is one of the main challenges in neuroscience. This is particularly defiant when situations change rapidly over time because of the intertwining of spatial and temporal information. However, understanding the cognitive processes that allow coping with dynamic environments is critical, as the nervous system evolved in them due to the pressure for survival. Recent experiments have revealed a new cognitive mechanism called time compaction. According to it, a dynamic situation is represented internally by a static map of the future interactions between the perceived elements (including the subject itself). The salience of predicted interactions (e.g. collisions) over other spatiotemporal and dynamic attributes during the processing of time-changing situations has been shown in humans, rats, and bats. Motivated by this ubiquity, we study an artificial neural network to explore its minimal conditions necessary to represent a dynamic stimulus through the future interactions present in it. We show that, under general and simple conditions, the neural activity linked to the predicted interactions emerges to encode the perceived dynamic stimulus. Our results show that this encoding improves learning, memorization and decision making when dealing with stimuli with impending interactions compared to no-interaction stimuli. These findings are in agreement with theoretical and experimental results that have supported time compaction as a novel and ubiquitous cognitive process.
SHAP as a Data Reduction Technique for Highly Imbalanced Big Data
Authors: Hancock John T. , Bauder Richard A. , Khoshgoftaar Taghi M.
Published: January 2025

Fraud detection through the classification of highly imbalanced Big Data is an exciting area of Machine Learning research. On the one hand, in certain fraud detection application domains, the use of One-Class classifiers is an overlooked opportunity. On the other hand, for researchers faced with the task of building Machine Learning models for identifying fraud, when only legitimate transaction data is available, One-Class Classifiers are indispensable. We investigate the efficacy of SHapley Additive exPlanations (SHAP) as a feature selection technique for One-Class classification tasks. In this study we utilize authentic data from the Credit Card fraud and Medicare insurance fraud application domains. Our contribution is to show that researchers can use SHAP in conjunction with One-Class Classifiers to do feature selection on highly imbalanced datasets, and then build models, with the selected features, that yield performance similar to, or better than, models built using all features. Our results in Big Medicare data fraud detection show that an over 90% data reduction through feature selection can nevertheless coincide with the best performance in terms of Area under the Precision Recall Curve.
The intersection polynomials of a virtual knot IV: Crossing change and supporting genus
Authors: Higa Ryuji , Nakamura Takuji , Nakanishi Yasutaka , Satoh Shin
Published: January 2025

In the previous papers, we introduced three intersection polynomials of a virtual knot. In this paper, we prove that the first and second intersection polynomials are finite-type invariants of order two with respect to crossing change. We also study virtual knots of supporting genus one, and give a relation between the first and second intersection polynomials of such a virtual knot.
A Null-Player Axiom for the Myerson Value in Partition Function form Games: A Note
Authors: Sánchez-Pérez Joss
Published: January 2025

In this work, we explore solutions for partition function form games, where our basic approach is rooted in a concept of null player, derived directly from the carrier concept of Myerson [(1977) Int. J. Game Theory 6(1), 23–31]. We then show that the Myerson value cannot be characterized with the standard translation of Shapley’s axioms of linearity, symmetry, efficiency and null-player to partition function form games. Instead, we provide an axiomatic characterization for the family of solutions for partition function form games satisfying those axioms, and we show that every such solution is a linear combination of specific marginal contributions of players.
Simultaneous and Sequential Abatement in a Differentiated Duopoly Under Linear and Quadratic Cost
Authors: Chandran Abhay , Wang Leonard F. S. , Ramani Vinay
Published: January 2025

In this paper, we examine the sequential versus simultaneous abatement choices of firms in a differentiated duopoly where the production decisions of firms lead to environmental damage. We consider two cases — one, where the production cost is linear and two, where the production cost is quadratic. Introducing product differentiation and quadratic cost yields nuanced results. First, considering linear production cost, we find that when the cost of abatement technology is high, the leader firm free rides on the follower firm by lowering the amount of abatement. Second, when the degree of product differentiation is very low, the abatement of the leader in the sequential case is lower than the abatement in the simultaneous case. For the follower, the opposite holds. Furthermore, the total abatement under the sequential case is lower than in the simultaneous case. The above findings continue to hold under quadratic cost. However, the comparison between sequential and simultaneous cases depends on the values of the cost of production and the degree of product differentiation. We then consider an alternative game in which the regulator can pre-commit and choose the tax before the firms make their abatement choices. In this case, the abatement investments are equal regardless of whether the firms move simultaneously or sequentially. Finally, we find that, under some parametric configurations, the total abatement when the regulator cannot pre-commit is greater than that when the regulator can pre-commit.
Mean-field equilibrium price formation with exponential utility
Authors: Fujii Masaaki , Sekine Masashi
Published: January 2025

In this paper, using the mean-field game theory, we study a problem of equilibrium price formation among many investors with exponential utility in the presence of liabilities unspanned by the security prices. The investors are heterogeneous in their initial wealth, risk-averseness parameter, as well as stochastic liability at the terminal time. We characterize the equilibrium risk-premium process of the risky stocks in terms of the solution to a novel mean-field backward stochastic differential equation (BSDE), whose driver has quadratic growth both in the stochastic integrands and in their conditional expectations. We prove the existence of a solution to the mean-field BSDE under several conditions and show that the resultant risk-premium process actually clears the market in the large population limit.
On the number of subdirect products involving semigroups of integers and natural numbers
Authors: Clayton Ashley , Reilly Catherine , Ruškuc Nik
Published: January 2025

In this paper, we extend a recent result that for the (additive) semigroup of positive integers [Formula: see text], there are continuum many subdirect products of [Formula: see text] up to isomorphism. We prove that for [Formula: see text] each one of [Formula: see text] (the group of integers), [Formula: see text] (the monoid of non-negative integers), or [Formula: see text], the direct product [Formula: see text] contains continuum many (semigroup) subdirect products up to isomorphism.
Cohomology of 𝒦(1) acting on the superspace of bilinear differential operators
Authors: Abdaoui Meher
Published: January 2025

We consider the [Formula: see text]-dimensional real superspace [Formula: see text] endowed with its standard contact structure defined by the [Formula: see text]-form [Formula: see text]. The conformal Lie superalgebra [Formula: see text] acts on [Formula: see text] as the Lie superalgebra of contact vector fields. We compute the first differential cohomology of [Formula: see text] with coefficients in superspace [Formula: see text] of bilinear differential operators acting on weighted densities. This work is the simplest super analog of the problems solved in Ref. 5.
Algebraic properties of the N = 1 BMS superalgebra
Authors: Gao Shoulan , Pei Yufeng , Xiao Mingyue
Published: January 2025

This paper investigates the algebraic properties of the Bondi–Metzner–Sachs (BMS) superalgebra, as initially introduced by G. Barnich, L. Donnay, J. Matulich and R. Troncoso, Asymptotic symmetries and dynamics of 3D flat supergravity, J. High Energy Phys. 2014 (2014) 071. We introduce a new realization of the BMS superalgebra using the Balinsky–Novikov construction. Utilizing this approach, we prove that the BMS superalgebra constitutes the unique minimal supersymmetric extension of the BMS algebra in three dimensions. Additionally, we compute the low-order cohomology groups of the BMS superalgebra and classify its derivations, central extensions, and automorphisms.
A Direct Maximum-Norm Error Estimator for Condensed Elements With Application to Adaptive Analysis of First-Order Initial-Value Problems
Authors: Yuan Quan , Yuan Si
Published: January 2025

This paper proposes a direct maximum-norm error estimator for the condensed element with application to the adaptive finite element (FE) analysis of the first-order initial-value problems (IVPs). Taking advantage of the ultra superconvergent nodal accuracy of the condensed element, the FE errors are analogized with the errors of the corresponding polynomial interpolation, which allows a direct calculation of the points and values of the maximum errors on each element in a simple and straightforward manner. Equipped with this error estimator, a complete adaptivity algorithm based on the condensed element is developed with reliable error control and effective step-size adjustment. Mathematical analysis and representative numerical examples of both linear and nonlinear IVPs of both single and system of equations are presented to show the validity and effectiveness of the proposed approach.