bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective immunity induced by a novel P1 adhesin C-terminal anchored mRNA vaccine against
Mycoplasma pneumoniae
infection in BALB/c mice
Authors: Zeng Qilin , Sun Peiyuan , Li Weiwei , Tang Yuanyuan , Hu Yuxuan , Zhou Jun , Zhou Yanxia , Chen Liesong , Yimou Wu 
Published: January 2025

ABSTRACT

Mycoplasma pneumoniae
(Mp), a unique pathogen devoid of a cell wall, is naturally impervious to penicillin antibiotics. This bacterium is the causative agent of
M. pneumoniae
pneumonia, an acute pulmonary affliction marked by interstitial lung damage. Non-macrolide medications may have potential adverse effects on the developmental trajectory of children, thereby establishing macrolides as the preferred treatment for
M. pneumoniae
in pediatric patients. However, the emergence of macrolide-resistant and multidrug-resistant strains of
M. pneumoniae
presents significant challenges to clinical management and public health. Vaccines, particularly those based on mRNA technology, are regarded as a promising avenue for preventing and controlling
M. pneumoniae
infections due to their inherent safety, immunogenicity, and adaptability. Our research delves into the P1 adhesin of
M. pneumoniae
, a protein that binds to host cell receptors with its immunodominant epitopes located at the carboxyl terminus, known to provoke robust immune responses and pulmonary inflammation. We have developed an mRNA vaccine harnessing this dominant antigenic epitope and assessed its protective immunity in BALB/c mice against
M. pneumoniae
infection. The vaccine elicited potent humoral and cellular immune responses, effectively diminishing inflammation. It notably decreased IL-6 levels in the lungs of infected mice and concurrently elevated IL-4, IL-10, and IFN-γ levels post-immunization. The vaccine also reduced pathological changes in the lungs and the
M. pneumoniae
DNA copy numbers in the infected animals. Collectively, these findings underscore the mRNA vaccine’s remarkable immunogenicity and protective potential against
M. pneumoniae
infections, offering valuable insights for the development of mRNA vaccines targeting mycoplasma infections.

IMPORTANCE

M. pneumoniae
, a bacteria without a cell wall, is known for causing pneumonia and is resistant to penicillin. The increasing prevalence of macrolide-resistant strains has complicated treatment options, emphasizing the need for new strategies. Our research explores an mRNA vaccine candidate that targets the P1 adhesin of
M. pneumoniae
, a protein critical for the bacteria’s interaction with host cells. In a mouse model, this vaccine has shown potential by inducing immune responses and suggesting a possible reduction in inflammation, as indicated by changes in cytokine levels and lung pathology. While further research is required, the vaccine’s preliminary results hint at a potential new direction in managing mycoplasma infections, offering a promising avenue for future therapeutic development. This study contributes to the ongoing search for effective preventive measures against
M. pneumoniae
.
Relapsing ANCA-associated vasculitis presenting as a mediastinal mass
Authors: Pieri Christopher , Challoner Benjamin , Giaslakiotis Konstantinos , Hawthorne Mark , Sheaff Michael , Rajakariar Ravindra 
Published: January 2025

Anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV) represent a heterogeneous multisystem group of disorders typified by necrotising inflammation of smaller blood vessels, classically yielding a pauci-immune, crescentic glomerulonephritis. Without prompt treatment, there is a significant risk of irreversible damage and ensuing renal impairment.Diagnosis is often challenging, exacerbated by the disorder’s often vague and insidious presentation. Even with known AAV, relapse can mimic other similarly serious conditions including infection or malignancy, with significant ramifications on respective downstream management options.Here, we present the case of a young man with pre-existing myeloperoxidase-positive vasculitis, describing a subacute cluster of symptoms and subsequently found to have an anterior mediastinal mass. Urgent tissue sampling excluded other aetiologies and ultimately delineated this as a surprising complication of vasculitis, allowing for prompt immunosuppression escalation. This case highlights the diagnostic challenge these patients represent, and the utility timely access to multimodality imaging holds alongside a multidisciplinary approach to expedite correct management decisions.
Acute therapeutic effects and pathophysiology of eosinophilic granulomatosis with polyangiitis neuropathy
Authors: Yamanaka Nanami , Takeshita Yukio , Sato Ryota , Nawata Takashi , Okafuji Tatsuya , Fujikawa Susumu , Fujisawa Miwako , Matsuo Kinya , Nemoto Joe , Mizumoto Yuki , Nishihara Hideaki , Honda Masaya , Oishi Mariko , Maeda Toshihiko , Shimizu Fumitaka , Koga Michiaki , Kanda Takashi , Nakamori Masayuki 
Published: January 2025

ObjectiveThis study investigated the effects of early treatment and pathophysiology on eosinophilic granulomatosis with polyangiitis neuropathy (EGPA-N).MethodsTwenty-six consecutive patients with EGPA-N were diagnosed and treated within a day of admission and underwent clinical analysis. Peripheral nerve recovery rates were evaluated after early treatment by identifying the damaged peripheral nerve through detailed neurological findings.ResultsThe eosinophil count at onset was significantly correlated with the total number of damaged nerves. There was a strong correlation between the timing of treatment and the recovery rate in patients who started treatment within 50 days, as the recovery rate did not increase after 50 days of treatment. Antineutrophil cytoplasmic antibodies (ANCA)-negative cases showed significantly higher recovery rates than ANCA-positive cases. Vasculitis was detected in 67% of ANCA-positive and 29% of ANCA-negative patients in the sural nerve and skin biopsy specimen. In addition, infiltration of eosinophils into peripheral nerve tissues was observed in 40% of ANCA-negative patients, whereas it was absent in ANCA-positive patients. Intrafascicular oedema was found in 95% of all patients.DiscussionOur results suggest three pathological pathways: (1) ischaemic peripheral nerve due to vasculitis mainly in ANCA-positive cases, (2) direct infiltration and degranulation of eosinophils in ANCA-negative cases and (3) progression of axonal ischaemia due to intrafascicular oedema in both cases. The study also found that ANCA-negative cases exhibited better responsiveness to acute-phase treatment than ANCA-positive cases. It is essential to treat patients with EGPA-N as early as possible because the patients could recover time-dependently within 50 days of the onset.
Understanding barriers to young people’s utilisation of sexual and reproductive health services in Asia-Pacific countries: a qualitative systematic review and thematic synthesis
Authors: Riabroi Watcharakorn , Gregory Benjamin , Mackay Daniel , Germeni Evi 
Published: January 2025

IntroductionBased on the United Nations’ sustainable development goals, universal access to sexual and reproductive health (SRH) services should be attained by 2030. Yet, large inequalities in adolescent SRH knowledge and service use still exist both within and between countries. The goal of this study was to identify and synthesise published qualitative research on factors affecting young people’s utilisation of SRH services in Asia-Pacific countries.MethodsWe systematically searched five electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science) for qualitative studies reporting the experiences, attitudes and views of young people (aged 10–24 years) regarding the utilisation of SRH services in Asia-Pacific countries. We assessed the quality of identified studies using the Critical Appraisal Skills Programme qualitative checklist and employed a thematic synthesis approach for the data analysis.ResultsWe included 31 articles that reported the experiences of over 1800 young people from 15 different countries. Thematic synthesis identified six descriptive themes that captured factors influencing SRH service utilisation: (1) navigating puberty; (2) knowledge and beliefs about SRH; (3) embarrassment and confidentiality concerns; (4) low decision-making autonomy; (5) traditional practices and religious beliefs; and (6) social and gender norms. Based on these, we developed an overarching analytical theme, ‘trapped in a legacy of shame’, which highlights the role of shame as a key emotion associated with young people’s utilisation of SRH services.ConclusionOur findings point towards the necessity of integrating shame-sensitive approaches and a social norms perspective in interventions aiming to improve young people’s SRH outcomes in Asia-Pacific countries.PROSPERO registration numberCRD42023389653.
How does news coverage of suicide affect suicidal behaviour at a high-frequency location? A 7-year time series analysis
Authors: Marzano Lisa , Spence Ruth , Marsh Ian , Barbin Arianna , Kruger Ian 
Published: January 2025

IntroductionNews reporting of suicide can have a significant influence on suicidal behaviour in the general population, especially following the death of a well-known individual. By comparison, the impact of reporting on suicides at well-known, ‘high-frequency’ locations is less well understood. We investigated the relationship between news coverage of suicide and incidents at a high-frequency coastal location in the UK over a 7-year period.MethodsWe analysed bidirectional associations (with daily and weekly lags) and Granger causality between suicide-related news in the UK (n=38 595, of which 789 focused on cliff locations) and suspected suicides (n=278) and crisis interventions (n=3050) at the site between 1 January 2017 and 31 December 2023. Separate subanalyses explored associations with repeat coverage and with headlines featuring explicit location/method details.ResultsWhile coverage of incidents at the study site and other coastal locations represents a small and decreasing proportion of all UK news of suicide, 51% of all cliff-related news focused on the study site, often explicitly identified in the story’s headline (81%). There were significant but small (r<0.3) correlations between the volume of news coverage (particularly when method-specific and location-specific) and suicidal behaviour at the site, with fatalities increasing in the immediate aftermath of reporting. This effect was strongest in 2018–2019 (which had the greatest volume of reporting and repeat coverage) but failed to reach significance in 2020–2023, when there were fewer reports, less repeat coverage and no headlines referring to multiple deaths at the site.ConclusionsFindings underscore the importance of continued efforts to monitor and improve the quality of news and other media portrayals of suicide. Follow-up studies, including qualitative research with people with lived/living experiences of suicide, could further explore how different types of news stories and wider narratives might contribute to increases—and potentially decreases—in suicides at high-frequency locations.
Neighbourhood socioeconomic conditions and emergency admissions for ambulatory care sensitive conditions in children: a longitudinal ecological analysis in England, 2012–2017
Authors: Franklin Courtney , Mason Kate , Akanni Lateef , Daras Konstantinos , Rose Tanith , Carter Bernie , Carrol Enitan D , Taylor-Robinson David 
Published: January 2025

BackgroundAmbulatory care sensitive conditions (ACSCs) are those for which hospital admission could be prevented by interventions in primary care. Children living in socioeconomic disadvantage have higher rates of emergency admissions for ACSCs than their more affluent counterparts. Emergency admissions for ACSCs have been increasing, but few studies have assessed how changing socioeconomic conditions (SECs) have impacted this. This study investigates the association between local SECs and emergency ACS hospital admissions in children in England.MethodsWe examined longitudinal trends in emergency admission rates for ACSCs and investigate the association between local SECs and these admissions in children over time in England, using time-varying neighbourhood unemployment as a proxy for SECs. Fixed-effect regression models assessed the relationship between changes in neighbourhood unemployment and admission rates, controlling for unmeasured time-invariant confounding of each neighbourhood. We also explore the extent to which this relationship differs by acute and chronic ACSCs and is explained by access to primary and secondary care.ResultsBetween 2012 and 2017, paediatric emergency admissions for acute ACSCs increased, while admissions for chronic ACSCs decreased. At the neighbourhood level, each 1% point increase in unemployment was associated with a 3.9% and 2.7% increase in the rate of emergency admissions for acute ACSCs, for children aged 0–9 years and 10–19 years, respectively. A 2.6% increase in admission rates for chronic ACSCs was observed, driven by an association in 0–9 years old. Adjustment for primary and secondary care access did not meaningfully attenuate the magnitude of this association.ConclusionsIncreasing trends in neighbourhood unemployment were associated with increases in paediatric emergency admission rates for ACSCs in England. This was not explained by available measures of differential access to care, suggesting policy interventions should address the causes of unemployment and poverty in addition to health system factors to reduce emergency admissions for ACSCs.
Real-world clinical utility of Xpert MTB/RIF Ultra in the assessment of tuberculosis in a low-TB-incidence, high-resource setting
Authors: Kim Jee Whang , Patel Hemu , Halliwell Richard , Free Robert C , Glimour-Caunt Alison , Pareek Manish , Woltmann Gerrit , Verma Raman , Perera Nelun , Haldar Pranabashis 
Published: January 2025

BackgroundTuberculosis (TB) diagnosis in the UK is impacted by delay and suboptimal culture-based microbiological confirmation rates due to the high prevalence of paucibacillary disease. We examine the real-world clinical utility of Xpert MTB/RIF Ultra (Xpert-Ultra) as a diagnostic test and biomarker of transmissible infection in a UK TB service.MethodsClinical specimens from suspected TB cases triple tested (smear microscopy, mycobacterial culture and Xpert-Ultra) at University Hospitals of Leicester NHS Trust (1 March 2018–28 February 2019) were retrospectively analysed. Diagnostic sensitivity and specificity were calculated using positive MTB culture and clinical TB diagnosis as reference standards. The QuantiFERON (QFT) positive proportion of pulmonary TB (PTB) contacts was used as a metric of transmitted infection to evaluate Xpert-Ultra and smear grade as markers of infectiousness.Results251 samples (188 respiratory) from 231 patients (86 TB) were analysed. Compared with microscopy, Xpert-Ultra had higher diagnostic sensitivity (24.7% vs 78.7%, p<0.001) and comparable specificity (97.5% vs 99.4%). Xpert-Ultra and culture had comparable sensitivity (78.7% vs 71.9%) and specificity (99.4% vs 100.0%). Incorporating Xpert-Ultra with culture increased microbiologically verified diagnosis to 91.7% for PTB and 75.9% for extrapulmonary TB, compared with 85.0% and 44.8%, using culture alone. In PTB, both smear and Xpert-Ultra grade were positively associated with the proportion of contacts testing QFT positive. However, Xpert-Ultra had a higher negative predictive value than smear (QFT-positive contacts 6.7% vs 17.7%).ConclusionIn low-TB-burden settings, systematic adoption of Xpert-Ultra for clinical assessment of suspected TB can improve the proportion of microbiologically verified diagnoses and improve the stratification of transmission risk.
Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE
Authors: Zeng Li , Yang Lijing , Zhang Yichen , Lan Tianzuo , An Yang , He Pengming , Wen Xueping , Deng Shaoping , Zhang Zhixin , Liu Jian , Zhou Qiao 
Published: January 2025

ObjectivesSLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire’s role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE.MethodsWe conducted an analysis of blood samples from 50 treatment-naive patients with SLE and 50 healthy donors, employing RNA extraction, high-throughput sequencing and subsequent bioinformatics analysis.ResultsOur findings revealed significant alterations in TRBV and TRBJ gene usage frequencies, indicative of a skewed TCR repertoire in patients with SLE. Notably, nine hub TRBV genes were identified as potential biomarkers for SLE with high diagnostic accuracy. Furthermore, we observed a reduction in TCR diversity, characterised by a lower diversity 50 value and increased clonal expansion, which correlated with disease severity.ConclusionsThe TCRβ repertoire is significantly altered in SLE, with potential implications for diagnostics and therapeutics. The identified hub genes may serve as novel biomarkers for SLE, and the findings contribute to the understanding of the immunopathogenesis of the disease.
Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry
Authors: Himmelreich Jelle C L , Virdone Saverio , Camm A John , Pieper Karen , Harskamp Ralf E , Verheugt Freek W A , Bassand Jean-Pierre , Misselwitz Frank , Pereira-Barretto Antônio C , Cools Frank , Gibbs Harry , Kakkar Ajay K 
Published: January 2025

AimsThis study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.Methods and resultsPatients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models. Among GARFIELD-AF patients on apixaban, 2570/3615 (71%) would have been eligible for ARISTOTLE. Among patients using rivaroxaban, 2005/4914 (41%) would have been eligible for ROCKET AF. Eligibility rates were steady over time, with minor differences across medical specialties. Real-world AF patients selected according to trial criteria had lower cardiovascular burden than the original trial participants, especially compared with ROCKET AF. HRs (95% CI) for apixaban versus VKA among ARISTOTLE-eligible users were 0.57 (0.34 to 0.94) for stroke/systemic embolism, 0.76 (0.48 to 1.20) for major bleeding and 0.89 (0.70 to 1.12) for all-cause mortality. Among ROCKET AF-eligible rivaroxaban users, HRs for rivaroxaban versus VKA were 0.90 (0.57 to 1.43), 0.92 (0.59 to 1.43) and 0.86 (0.69 to 1.08), respectively. All safety and efficacy estimates were similar to those in the original trials.ConclusionReal-world representativeness of the selection criteria was greater for ARISTOTLE than ROCKET AF. The pivotal randomised trials of apixaban and rivaroxaban versus warfarin can be successfully emulated in real-world AF patients by applying trial-specific selection criteria and appropriate methodology for non-randomised treatment allocation.Trial registration numberNCT01090362.
Firearm injury survivors report extreme high risk for poor physical and mental health outcomes early after hospital discharge necessitating multidisciplinary care
Authors: Biesboer Elise A , Brandolino Amber , Tomas Carissa W , Johnson Isabel R , deRoon-Cassini Terri , Timmer-Murillo Sydney , Schroeder Mary Elizabeth , DeMoya Marc , Trevino Colleen 
Published: January 2025

BackgroundUp to 20–40% of survivors of any traumatic injury develop post-traumatic stress disorder (PTSD) or depression after injury. Firearm injury survivors may be at even higher risk for adverse outcomes. We aimed to characterize PTSD and depression risk, pain symptoms, and ongoing functional limitations in firearm injury survivors early after hospital discharge.MethodsFirearm injury survivors seen in the Trauma Quality of Life (TQOL) outpatient follow-up clinic 1–2 weeks after discharge were invited to participate in a survey assessing both mental and physical health outcomes. The survey included the Brief Pain Inventory (BPI), the Injured Trauma Survivor Screen (ITSS), the Beck Depression Inventory (BDI), the PTSD Checklist for DSM-5 (PCL-5), and the 12-item Short Form Survey Physical Health component (SF-12)Results306 patients were seen in the TQOL Clinic, and 175 responded to the survey. The mean age was 32 years (SD=12), 81% were male, and 79% were black. On the ITSS, 69% and 48% of patients screened risk positive for PTSD and depression, respectively. Patients reported mild depression symptoms with an average BDI score of 14.3 (SD=11.8) and elevated PTSD symptoms with an average PCL-5 score of 43.8 (SD=12.8). Patients with severe BPI scores were more likely to screen positive for depression and PTSD. Respondents scored >2 SD below the US national average on the SF-12 for physical quality of life (M=28.7). 12% of patients were at risk across all four domains of pain, PTSD, depression, and physical function.ConclusionEarly after discharge, over two-thirds of firearm injury survivors were at risk for the development of PTSD, nearly half were at risk of depression, and physical function was significantly decreased. Trauma centers need to prioritize early, outpatient multidisciplinary care to treat and prevent the development of poor chronic physical and mental health for firearm injury survivors.Level of evidenceIII.
On the Klein–Gordon scalar field oscillators in a spacetime with spiral-like dislocations in external magnetic fields
Authors: Mustafa Omar , Guvendi Abdullah 
Published: January 2025

Abstract
We investigate the effects of two types of spiral dislocation (the distortion of the radial line, labeled as spiral dislocation I, and the distortion of a circle, labeled as spiral dislocation II) on the relativistic dynamics of the Klein–Gordon (KG) oscillator fields, both in the presence and absence of external magnetic fields. In this context, our investigations show that while spiral dislocation I affects the energies of the KG oscillators (with or without the magnetic field), spiral dislocation II has, interestingly, no effect on the KG oscillator’s energies unless a magnetic field is applied. However, for both types of spiral dislocations, we observe that the corresponding wave functions incorporate the effects of the dislocation parameter. Our findings are based on the exact solvability and conditional exact solvability (associated with the biconfluent Heun polynomials) of the KG oscillators (with or without the magnetic field, respectively) for spiral dislocation I, and the exact solvability of the KG oscillators (with or without the magnetic field) for spiral dislocation II. The exact solvability of the latter suggests that the oscillator’s frequency is solely determined by the magnetic field strength.