bluuebunny/crossref_metadata_2025_split huggingface dataset:
An overview of the laboratory diagnosis of
Pneumocystis jirovecii
pneumonia
Authors: Jaramillo Cartagena Alexis , Asowata Osaretin Emmanuel , Ng Dianna , Babady N. Esther 
Published: February 2025

ABSTRACT

Pneumocystis jirovecii
(
P. jirovecii
) is a fungal pathogen associated with significant morbidity in immunocompromised patients, including both HIV- and non-HIV-infected patients. The nonspecific clinical and radiological presentation makes clinical diagnostic challenging, emphasizing the need for accurate laboratory diagnostic tests. However,
P. jirovecii
does not grow in routine culture media, which presents diagnostic challenges in the laboratory as well. Recent publications from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium continue to rely on direct detection of
P. jirovecii
organisms in tissues and respiratory samples to define proven
P. jirovecii
pneumonia (PCP) even as the sensitivity of these methods are lower. Novel, standardized methods are needed to improve the clinical and laboratory diagnosis and management of PCP. This minireview provides an overview of current diagnostic tests for PCP and emerging applications that aim at filling existing diagnostic gaps and providing more accurate and less invasive diagnoses for this significant disease.
Coding-complete genome sequence of a bovine viral diarrhea virus subgenotype 1v strain isolated in China
Authors: Gao Shandian , Liu Wei , Shao Junjun , Zhang Yun , Guo Huichen , Chang Huiyun , Wang Jiandong 
Published: February 2025

ABSTRACT

We sequenced the coding-complete genome sequence of bovine viral diarrhea virus (BVDV) strain NX2019/02. It belongs to the 1v subgenotype. This report will increase our understanding of the epidemiology of BVDV in China.
Interspecies signaling modulates the biosynthesis of antimicrobial secondary metabolites related to biological control activities of
Pseudomonas fluorescens
2P24
Authors: Zhang Nannan , Zhu Xianfeng , Tao Xuanying , Li Jie , Tang Qi , Liu Xiaochun , Luo Li-Ming , Zhang Pingping , Zhang Li-Qun , He Yong-Xing , Ge Honghua 
Published: February 2025

ABSTRACT

Signaling between rhizosphere microorganisms is crucial in bacteria interaction and communication, shaping the rhizomicrobiome. Plant growth-promoting bacterium
Pseudomonas
produces a spectrum of important antibiotics to inhibit plant pathogens, albeit with an associated metabolic burden. Antibiotics could function as intra- and interspecies signals at subinhibitory concentrations to coordinate gene expression and microbial behaviors. In this work, we characterized pyoluteorin as an interspecies signal that modulates the biosynthesis of 2,4-diacetylphloroglucinol (2,4-DAPG), a broad-spectrum biocontrol agent, in non-pyoluteorin-producing
Pseudomonas fluorescens
2P24. We demonstrated that the key transcriptional repressor PhlF from the 2,4-DAPG biosynthetic gene cluster spontaneously senses pyoluteorin, enhancing repression of the
phlA
promoter activity and inhibiting 2,4-DAPG synthesis in
P. fluorescens
2P24. Pyoluteorin also binds to another transcriptional repressor, PhlH, from the 2,4-DAPG biosynthetic gene cluster, subsequently releasing the transcription of
phlG
, which facilitates the hydrolysis of 2,4-DAPG. Both PhlF and PhlH are simultaneously involved in sensing exogenous pyoluteorin to regulate the 2,4-DAPG biosynthetic operon, playing a crucial role in controlling antibiotic metabolites in response to environmental changes. Further phylogenetic and structural analyses demonstrated that PhlH and PhlF are widely distributed across
Pseudomonas
spp. with conserved ligand-binding domains. The findings shed new light on the regulatory mechanism of 2,4-DAPG biosynthesis underlying interspecies signaling by pyoluteorin and provide invaluable clues for the rational design of co-inhabiting
Pseudomonas
spp. as biocontrol agents.

IMPORTANCE

Rhizosphere microorganisms release vital signals that shape microbial communities, with antibiotics at low concentrations acting as intra- and interspecies signals. However, the mechanisms of these signals in coordinating gene expression are unclear. In non-pyoluteorin-producing
Pseudomonas fluorescens
2P24, pyoluteorin was identified as an interspecies signal that regulates the
phl
biosynthesis gene cluster for 2,4-DAPG production. TetR family repressors PhlH and PhlF were found to positively regulate 2,4-DAPG hydrolysis and negatively regulate its synthesis in response to pyoluteorin. Structural modeling and docking analyses revealed the interactions between pyoluteorin and both PhlH and PhlF, modulating gene expression. Phylogenetic analyses showed a wide distribution of PhlH and PhlF across
Pseudomonas
spp. with conserved ligand-binding domains. These findings deepen our understanding of interspecies signaling mechanisms and highlight the potential for designing co-inhabiting
Pseudomonas
spp. as effective biocontrol agents.
Gut microbiome features associate with immune checkpoint inhibitor response in individuals with non-melanoma skin cancers: an exploratory study
Authors: Zhao Yujie , Ferri Jacqueline T. , White James R. , Schollenberger Megan D. , Peloza Kim , Sears Cynthia L. , Lipson Evan J. , Shaikh Fyza Y. 
Published: February 2025

ABSTRACT

Immune checkpoint inhibitor (ICI) therapy has yielded revolutionary outcomes among some individuals with skin cancer, but a large percentage of individuals do not benefit from these treatments. The gut microbiota is hypothesized to impact ICI therapy outcomes. However, data on ICI therapy, gut microbiota, and non-melanoma skin cancers are limited. To examine the association of gut microbiota structure and function with non-melanoma skin cancer ICI outcomes, we performed 16S rRNA V1-V2 gene amplicon sequencing of 68 fecal samples collected longitudinally from individuals with basal cell carcinoma (
n
= 5), Merkel cell carcinoma (
n
= 5), or cutaneous squamous cell carcinoma (CSCC,
n
= 11), followed by tumor-dependent differential analyses of bacterial composition and fecal sample analysis by untargeted metabolomics. Across all tumor types, we identified 10 differential bacterial genera between responders (R) or non-responders (NR) to ICI therapy. Among individuals with CSCC, we identified 10 genera and 20 species that differentiated between R and NR and yielded 8 pathways enriched in NR and 12 pathways enriched in R by predicted functional pathway analyses. Untargeted fecal metabolomics to examine putative gut microbiota metabolites associated with CSCC ICI R/NR identified nine KEGG pathways associated with ICI efficacy. In summary, this exploratory study suggests gut microbiota features that are associated with ICI efficacy in individuals with non-melanoma skin cancers and highlights the need for larger studies to validate the results.

IMPORTANCE
Prior studies examining associations between ICI efficacy and the gut microbiome have focused primarily on individuals with melanoma, for whom ICI therapy was first approved. Meanwhile, data regarding microbiome features associated with ICI responses in individuals with non-melanoma skin cancers (NMSCs) have remained limited. This initial fecal microbiota examination of individuals with NMSCs suggests that larger-scale studies to extend and validate our findings may yield predictive or prognostic biomarkers for individuals with NMSC receiving ICI with potential to provide insight to complementary, effective therapeutic interventions through microbiota modification.
Evaluating lipid-lowering drug targets for full-course diabetic retinopathy
Authors: Cao Jiahui , Su Ting , Chen Shuilian , Du Zijing , Lai Chunran , Chi Kaiyi , Li Qinyi , Wang Shan , Wu Qiaowei , Hu Yunyan , Fang Ying , Hu Yijun , Zhu Zhuoting , Huang Yu , Zhang Xiayin , Yu Honghua 
Published: February 2025

BackgroundImplementing lipid control in patients with diabetes is regarded as a potential strategy for halting the advancement of diabetic retinopathy (DR). This study seeks to use Mendelian randomisation (MR) to assess the causal relationship between lipid traits and lipid-lowering drug targets and full-course DR (background DR, severe non-proliferative DR (NPDR) and proliferative DR (PDR)).MethodsA two-sample MR and drug target MR to decipher the causal effects of lipid traits and lipid-lowering drug targets on full-course DR, including background DR, severe NPDR and PDR, was conducted in the study. Genetic variants associated with lipid traits and genes encoding the protein targets of lipid-lowering drugs were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data of full-course DR are obtained from FinnGen.ResultsNo significant causal relationship was found between lipid traits and full-course DR. However, in drug target MR analysis, peroxisome proliferator-activated receptor gamma (PPARG) enhancement was associated with lower risks of background DR (OR=0.12, p=0.005) and PDR (OR=0.25, p=0.006). Additionally, mediation MR analysis showed that lowering fasting insulin (p=0.015) and HbA1c (p=0.005) levels mediated most of the association between PPARG and full-course DR.ConclusionsThis study reveals PPARG may be a promising drug target for full-course DR. The activation of PPARG could reduce the risk of full-course DR, especially background DR and PDR. The mechanism of the PPARG agonists’ protection of full-course DR may be dependent on the glucose-lowering effect.
Acceptability of the R21/Matrix-M malaria vaccine alongside existing malaria interventions in the trial context
Authors: Diawara Halimatou , Grant Jane , Dicko Alassane , Traore Seydou , Issiaka Djibrilla , Koita Fatoumata , Datoo Mehreen , Sylla Mala , Dicko Abdrahmane Boncane , Sagara Issaka , Chandramohan Daniel , Hill Adrian VS , Greenwood Brian , Webster Jayne 
Published: February 2025

BackgroundThe R21/Matrix-M malaria vaccine has been shown to provide high protective efficacy against malaria in a phase III trial, and has been recommended for use by WHO. The vaccine will soon be deployed at scale in sub-Saharan Africa. This study aimed to understand the caregiver and community acceptability of the R21/Matrix-M vaccine alongside existing malaria prevention interventions, according to the communities of participants in the seasonal R21/Matrix-M phase III trial in Mali.MethodsQualitative data were collected to assess the acceptability of the R21/Matrix-M vaccine alongside the three R21/Matrix-M or control vaccine priming injections given in the first year of the trial. A total of 33 in-depth interviews (IDIs), 12 focus group discussions (FGDs) and 45 exit interviews at the trial clinics were conducted with caregivers of trial participants, 18 IDIs and 8 FGDs were conducted with community members, 13 IDIs with community health workers and 8 IDIs with trial field staff. Data were coded using the constructs from Sekhon’s theoretical framework on acceptability.ResultsAcceptability of the R21/Matrix-M vaccine was driven mainly by the high burden of malaria in the highly seasonal study area and consequent demand for a malaria vaccine, a perceived high efficacy of the R21/Matrix-M vaccine, and a high level of trust and confidence in the trial and trial team. These perceptions of the acceptability of the R21/Matrix-M vaccine led to a reduced perceived importance of seasonal malaria chemoprevention (SMC) among some caregivers, while others viewed R21/Matrix-M, SMC and insecticide-treated nets as complementary.ConclusionsThe R21/Matrix-M vaccine was acceptable to caregivers and communities of participants in the R21/Matrix-M phase III trial in Mali. Implementation research is needed to evaluate and ensure co-coverage of complementary malaria control interventions, including SMC in seasonal settings, in the face of the scale-up of R21/Matrix-M and other malaria vaccines.
Modelling the health, financial protection and equity impacts of upscaling the ACT NOW early intervention breast cancer pilot program in the Philippines: an extended cost-effectiveness analysis
Authors: Chye Alexander , Jan Stephen , Pathy Nirmala Bhoo , Luna Herdee Gloriane C , Lim Soledad B , Kimman Merel , Woodward Mark , Peters Sanne , Monaghan Helen , Ngelangel Corazon A , Angell Blake 
Published: February 2025

IntroductionWomen in the Philippines experience significant health and economic burdens of breast cancer. The Philippines has reformed financial protection for breast cancer but does not have a national early detection and treatment programme. This study aims to model the health and economic impacts of ACT NOW (a pilot breast cancer programme that navigates women through free early detection to treatment) through an extended cost-effectiveness analysis.MethodsA microsimulation decision tree model was used to model the ACT NOW intervention (including annual clinical breast examination (CBE) and biannual breast ultrasound for women at high risk of breast cancer) over 5 years for healthy women 40–69 years old. Outcomes included health gains (breast cancer deaths saved), financial protection (financial catastrophes saved) and incremental cost-effectiveness ratios (ICER) (cost per disability-adjusted life year (DALY) saved). Outcomes were stratified by income group. Probabilistic, one-way sensitivity and scenario analyses explored uncertainty.ResultsOver 5 years, the ACT NOW intervention is cost-effective with an ICER of PHP60 711 (USD1098) (average incremental cost PHP743 [95% UI 424–960] and DALYs saved 0.01 [95% UI 0.01–0.02], below Philippines 2022 gross domestic product per capita PHP178 751). Per 100 000 women, 57 deaths and eight financial catastrophes were saved. Cost-effectiveness did not vary significantly by income, but higher income groups incurred greater costs and lower DALYs. Results were sensitive to proportion of late-stage breast cancers post intervention, treatment adherence, intervention costs and downstaging effectiveness. Trade-offs are apparent between government contributions to financial protection and rates of financial catastrophe.ConclusionsEarly detection interventions (annual CBE, biannual breast ultrasound if at high risk of breast cancer) are likely to be cost-effective, reduce breast cancer-related mortality through detection at earlier stages and modestly effective in reducing the incidence of financial catastrophe. Further research is required to establish the best implementation model to pursue full implementation and ways of designing equity-based screening interventions.
Co-producing a safe mobility and falls informatics platform to drive meaningful quality improvement in the hospital setting: a mixed-methods protocol for theinsightFallstudy
Authors: Lear Rachael , Averill Phoebe , Carenzo Catalina , Tao Rachel , Glampson Ben , Leon-Villapalos Clare , Latchford Robert , Mayer Erik 
Published: February 2025

IntroductionManual investigation of falls incidents for quality improvement is time-consuming for clinical staff. Routine care delivery generates a large volume of relevant data in disparate systems, yet these data are seldom integrated and transformed into real-time, actionable insights for frontline staff. This protocol describes the co-design and testing of a safe mobility and falls informatics platform for automated, real-time insights to support the learning response to inpatient falls.MethodsUnderpinned by the learning health system model and human-centred design principles, this mixed-methods study will involve (1) collaboration between healthcare professionals, patients, data scientists and researchers to co-design a safe mobility and falls informatics platform; (2) co-production of natural language processing pipelines and integration with a user interface for automated, near-real-time insights and (3) platform usability testing. Platform features (data taxonomy and insights display) will be co-designed during workshops with lay partners and clinical staff. The data to be included in the informatics platform will be curated from electronic health records and incident reports within an existing secure data environment, with appropriate data access approvals and controls. Exploratory analysis of a preliminary static dataset will examine the variety (structured/unstructured), veracity (accuracy/completeness) and value (clinical utility) of the data. Based on these initial insights and further consultation with lay partners and clinical staff, a final data extraction template will be agreed. Natural language processing pipelines will be co-produced, clinically validated and integrated with QlikView. Prototype testing will be underpinned by the Technology Acceptance Model, comprising a validated survey and think-aloud interviews to inform platform optimisation.Ethics and disseminationThis study protocol was approved by the National Institute for Health Research Imperial Biomedical Research Centre Data Access and Prioritisation Committee (Database: iCARE—Research Data Environment; REC reference: 21/SW/0120). Our dissemination plan includes presenting our findings to the National Falls Prevention Coordination Group, publication in peer-reviewed journals, conference presentations and sharing findings with patient groups most affected by falls in hospital.
Protocol for an adaptive platform trial of intended service user-derived interventions to equitably reduce non-attendance in eye screening programmes in Botswana, India, Kenya and Nepal
Authors: Allen Luke , Kim Min , Tlhajoane Malebogo , Macleod David , Nkomazana Oathokwa , Gichangi Michael , Mishra Sailesh , Sabherwal Shalinder , Carpenter James R , Karanja Sarah , Ho-Foster Ari , Ratshaa Bakgaki , Bolster Nigel , Ramke Jacqueline , Burton Matthew J , Bastawrous Andrew 
Published: February 2025

IntroductionOnly 30%–50% of people referred to clinics during community-based eye screening are able to access care in Botswana, India, Kenya and Nepal. The access rate is even lower for certain population groups. This platform trial aims to test multiple, iterative, low-risk public health interventions and simple service modifications with a series of individual randomised controlled trials (RCT) conducted in each country, with the aim of increasing the proportion of people attending.Methods and analysisWe will set up a platform trial in each country to govern the running of a series of pragmatic, adaptive, embedded, parallel, multiarm, superiority RCTs to test a series of service modifications suggested by intended service users. The aim is to identify serial marginal gains that cumulatively result in large improvements to equity and access. The primary outcome will be the probability of accessing treatment among the population group with the worst access at baseline. We will calculate Bayesian posterior probabilities of clinic attendance in each arm every 72 hours. Each RCT will continually recruit participants until the following default stopping rules have been met: >95% probability that one arm is best; >95% probability that the difference between the best arm and the arms remaining in the trial is <1%; or 10 000 people have been recruited. Lower thresholds may be used for RCTs testing interventions with very low risks and costs. The specific design of cluster RCTs will be determined by our research team once the intervention is known, but the population and outcome will be the same across all trials.This adaptive platform trial will be used to identify effective service modifications, driving continuous improvements in access.Ethics and disseminationThis trial has been approved by the research ethics committee at the London School of Hygiene & Tropical Medicine (ref: 29549). Approvals for individual interventions will be sought from UK and local ethics committees. Results will be shared via local workshops, social media and peer-reviewed publications.Trial registration numberISRCTN53970958.
mHealth Intervention for Dementia Prevention through lifestyle Optimisation (MIND-PRO) in a primary care setting: protocol for a randomised controlled trial in people with low SES and/or migration background
Authors: van der Endt Anne Roos , Hoevenaar-Blom Marieke P , Galenkamp Henrike , Kas Martien J H , van den Berg Esther , Handels Ron , Moll van Charante Eric P , Richard Edo 
Published: February 2025

IntroductionThe Mobile Health (mHealth) Intervention for Dementia Prevention through lifestyle Optimisation (MIND-PRO) study addresses the increasing prevalence of dementia among populations with lower socio-economic status (SES) and/or a migration background. The study aims to evaluate the effectiveness and implementation of an mHealth intervention designed for self-managing lifestyle modifications with remote coaching to reduce dementia risk factors.Methods and analysisThis prospective randomised open-label blinded end point (PROBE) trial follows a type 2 hybrid effectiveness-implementation design with a 12-month intervention period. It aims to recruit 692 participants in Dutch primary care. Entry criteria include age 50–75 years, low SES and/or migration background, one or more dementia risk factors (hypertension, dyslipidaemia, diabetes mellitus, physical inactivity, smoking, depression and overweight) or manifest cardiovascular disease and possession of a smartphone. Participants are randomised to a coach-supported, interactive app facilitating self-management of dementia risk factors or to a control app with static health information. The primary effectiveness outcome is a composite score of systolic blood pressure, non-high-density lipoprotein cholesterol and body mass index. Implementation outcomes include coverage, adoption, acceptability, appropriateness, feasibility, fidelity, costs and sustainability of the intervention. Secondary outcomes include the Cardiovascular Risk Factors, Ageing and Dementia risk score and its individual risk factors, and disability, physical activity, depressive symptoms, cognitive functioning and daily distance moved.Ethics and disseminationThe MIND-PRO trial is funded by the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10510032120004) and approved by the Ethics Committee of Amsterdam UMC (reference: METC 2023.0770). Results are expected in 2026 and will be submitted for publication in a peer-reviewed journal, and presented at scientific conferences.Trial registration numberISRCTN92928122.
Effectiveness of midwife/nurse-led non-invasive uterine massage in preventing postpartum haemorrhage: a quantitative systematic review protocol
Authors: Kongvattananon Puangpaka , Sosome Boonsurb , Chunuan Sopen , Punsomreung Treechada , Varachanonth Panida , Bhatarasakoon Patraporn 
Published: February 2025

IntroductionPostpartum haemorrhage (PPH) negatively impacts women’s health. Preventing and managing PPH is important, and nurse-led interventions are needed. However, no systematic review has evaluated the effectiveness of non-invasive uterine massage for PPH prevention. Therefore, this systematic review aims to assess the efficacy of midwife/nurse-led intervention in managing PPH, serving as the best available evidence to develop further guidelines and recommendations in practice and policy-making.Methods and analysisThis systematic review will follow the JBI methodology for systematic reviews of effectiveness. The search will be conducted in the MEDLINE (PubMed), CINAHL (EBSCO), BENTHUM Science, JBI, Cochrane, ThaiJo and Google Scholar databases. Studies will be included in English and Thai and published between 2015 and 2024. Two independent reviewers will conduct the review, with data extraction and quality evaluation. Studies will be pooled in a statistical meta-analysis using JBI System for the Unified Management, Assessment and Review of Information or other software where possible.Ethics and disseminationThis systematic review does not require formal ethical approval because all data will be analysed anonymously. The results will provide an overall review and evidence of midwife/nurse-led non-invasive uterine massage intervention in preventing PPH. These findings will be disseminated through peer-reviewed publications.PROSPERO registration numberCRD42024566382