bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of stool-based Xpert MTB/RIF assay in the diagnosis of presumptive pulmonary tuberculosis in adults unable to expectorate sputum
Authors: Xue Yi , Chen Siyi , Zhang Weihe , Jia Junnan , Wang Fen , Dong Lingling , Zhao Liping , Huang Hairong , Yu Xia 
Published: February 2025

ABSTRACT

This study aimed to compare the performance of stool-based Xpert MTB/RIF(Xpert) assay (Cepheid, USA) against that of smear, culture, and Xpert using respiratory tract specimens (RTS) and stool samples in the diagnosis of adult pulmonary tuberculosis (PTB). This prospective study of patients with presumptive PTB was conducted at the Beijing Chest Hospital from January 2021 to December 2021. The smear test by fluorescence microscope, MGIT 960 liquid culture, and Xpert MTB/RIF assay was performed simultaneously on the RTS and stool samples. Patients were grouped based on the RTS examination results and clinical diagnosis. A total of 434 eligible patients were enrolled. Among these, 351 patients were diagnosed as PTB, while 83 patients were diagnosed as non-TB patients. Using RTS as standard sample, the sensitivity of smear on stool, culture on stool, Xpert on stool, and Xpert on RTS was 13.39% (47/351), 22.22% (78/351), 45.30% (159/351), and 66.10% (232/351), respectively. Furthermore, the specificity of Xpert on RTS and stool was 100% (83/83) for both specimens. Among the 48 patients with PTB confirmed by bronchoalveolar lavage fluid (BALF) examination, 16 had stool specimens with positive Xpert results. Similarly, among 200 patients diagnosed through sputum examination, 133 had positive Xpert results on stool specimens. Thus, Xpert on stool specimens may be a promising and practical strategy to improve PTB diagnosis, particularly among patients unable to expectorate sputum.

IMPORTANCE
This study aimed to assess the value of the Xpert MTB/RIF assay (Xpert) for diagnosing PTB using stool samples from adults in low HIV prevalence settings. Although the diagnostic yield of Xpert on stool samples is inferior to that of Xpert on RTS, stool-based Xpert may be useful in diagnosing patients with presumptive PTB who cannot expectorate sputum and do not opt for BALF collection.
Hyperpiliation, not loss of pilus retraction, reduces
Pseudomonas aeruginosa
pathogenicity
Authors: Kilmury Sara L. N. , Graham Katherine J. , Lamers Ryan P. , MacNeil Lesley T. , Burrows Lori L. 
Published: February 2025

ABSTRACT

Type IVa pili (T4aP) are important virulence factors for many bacterial pathogens. Previous studies suggested that the retraction ATPase, PilT, modulates pathogenicity due to its critical role in pilus dynamics and twitching motility. Here we use a
Caenorhabditis elegans
slow-killing model to show that hyperpiliation, not loss of pilus retraction, reduces virulence of
Pseudomonas aeruginosa
strains PAK and PA14. Hyperactivating point mutations in the
P. aeruginosa
PilSR two-component system that controls transcription of the major pilin gene,
pilA
, increased levels of surface pili to the same extent as deleting
pilT
, without impairing twitching motility. These functionally hyperpiliated PilSR mutants had significant defects in pathogenicity that were rescued by deleting
pilA
or through disruption of hyperpiliation via deletion of the type III secretion system needle-length regulator, PscP. Hyperpiliated
pilT
deletion or
pilO
point mutants showed similar PilA-dependent impairments in virulence, validating the phenotype. Together, our data support a model where a surfeit of pili reduces virulence, potentially through the prevention of effective engagement of contact-dependent virulence factors. These findings suggest that the role of T4aP retraction in virulence should be revised.

IMPORTANCE

Pseudomonas aeruginosa
is a major contributor to hospital-acquired infections and particularly problematic due to its intrinsic resistance to many front-line antibiotics. Strategies to combat this and other important pathogens include the development of anti-virulence therapeutics. We show that the pathogenicity of
P. aeruginosa
is impaired when the amount of T4aP expressed on the cell surface increases, independent of the bacteria’s ability to twitch. We propose that having excess T4aP on the cell surface may physically interfere with productive engagement of the contact-dependent type III secretion toxin delivery system. A better understanding of how T4aP modulate interaction of bacteria with target cells will improve the design of therapeutics targeting components involved in the regulation of T4aP expression and function to reduce the clinical burden of
P. aeruginosa
and other T4aP-expressing bacteria.
Human bocavirus-1 infection in hospitalized pediatric patients with acute respiratory tract infections
Authors: Tan Jie , Huang Ziyin , Tang Wenting , Liu Guangbing , Li Peiqun , Wen Jiaqi , Mo Lishai , Yan Chenglan , Dang Zhao , Huang Huiping , Li Qifei , Fu Chunyun 
Published: February 2025

ABSTRACT

Human bocavirus-1 (HBoV1) is an emerging viral pathogen associated with acute respiratory tract infections (ARTIs) in pediatric populations. This study aimed to evaluate the infection status and clinical characteristics of HBoV1 among hospitalized children suffering from ARTIs. A cohort of 5,021 pediatric patients with respiratory infections was analyzed using targeted next-generation sequencing to identify HBoV1 and other co-existing respiratory pathogens. Results indicated a detection rate of HBoV1 of 8.48%, predominantly among infants under 24 months, with a higher prevalence observed in males. Among the 426 children with HBoV1 detected, there were 17 cases (4%) of single HBoV1 infection, and 409 cases (96%) were co-infected with HBoV1 and other pathogens. The predominant infection pattern was HBoV1-bacteria-virus co-infection (155 cases). A total of 48 other pathogens were detected in children with HBoV1 co-infections, with rhinovirus and human herpesvirus being the most common. The median hospitalization duration for the children with HBoV1 was 8 days, and 16.26% required ICU admission for monitoring. The study offers a comprehensive analysis of the distribution of co-infecting pathogens, clinical features, and outcomes in hospitalized children with HBoV one infection.

IMPORTANCE
There is currently a poor understanding of the characteristics and clinical manifestations of human bocavirus-1 (HBoV1) infection. In the past decade, few studies have thoroughly analyzed co-infecting pathogens, such as viruses, bacteria, and fungi and their patterns in relation to HBoV1. This study utilizes targeted next-generation sequencing (tNGS) technology to identify HBoV1 and other common respiratory pathogens in 5,021 hospitalized children suffering from respiratory infections in the Guangxi region. It offers a detailed analysis of the distribution of co-infecting pathogens, infection patterns, laboratory findings, clinical manifestations, imaging features, complications, and prognoses related to HBoV1 infection in this population. The study highlights the high co-infection rates associated with HBoV1 and offers important insights for diagnosing, treating, and managing children with HBoV1 infection.
The establishment and optimization of a
Mycoplasma pneumoniae
detection system based on ERA-CRISPR/Cas12a
Authors: Yang Fo , Wu Qianlin , Zeng Xiaotong , Jiang Qiuyang , Zhang Shanshan , Wang Jin , Zhang Qi , Li Feng , Xu Dayong 
Published: February 2025

ABSTRACT

Mycoplasma pneumoniae
(MP) is a significant pathogen associated with community-acquired pneumonia, with considerable infectious risks posed, particularly to children and immunocompromised individuals. The current methods for detecting MP in research and clinical settings are recognized as time-consuming, instrument-dependent, and prone to non-specific cross-reactivity. Therefore, the creation of a rapid and sensitive detection method is urgently required. In this study, the MP-ERA-Cas12a system, integrating enzyme restriction amplification (ERA) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a technology, was introduced. Three detection methods were evaluated: the two-pot system, a modified one-pot system, and a lateral flow assay (LFA) strip-based system. In the one-pot system, the amplification and detection steps were consolidated within a single reaction vessel, effectively minimizing the risk of contamination and false positives that may arise from the handling of multiple tubes. It was observed that the one-pot system generated a fluorescent signal within 1 h and produced 1.6 times higher fluorescence signal intensity compared to the two-pot system, achieving a detection limit of 1 copy/μL. In contrast, the LFA system facilitated rapid on-site screening, with visible band results appearing on the strip within 5 min of the reaction, and a detection limit of 10
2
copies/μL was achieved. High specificity for MP was demonstrated by all methods. Significant advantages, including rapid processing, the absence of complex instrumentation, and ease of use are offered by this detection system, making it particularly suitable for resource-limited clinical settings. The system is seen as an efficient tool for the early diagnosis of MP, with substantial public health and clinical relevance.

IMPORTANCE

This study successfully combined enzyme restriction amplification (ERA) with the specific detection capabilities of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a. Based on the two-pot system established before, the one-pot system and lateral flow assay (LFA) system were developed for
Mycoplasma pneumoniae
(MP) detection. The MP-ERA-Cas12a system eliminates the need to open the lid during the reaction, reducing aerosol contamination, and minimizing the risk of false positives. The method does not require the use of advanced instruments or equipment and shows strong specificity while not being affected by other pathogens. As a new method of MP detection, the MP-ERA-Cas12a system has an important practical application prospect.
PD-1 inhibitor-induced thyroiditis and ACTH deficiency
Authors: Shah Nayab , Prentice David , Jayasundera Chandrin 
Published: February 2025

A woman in her 70s on pembrolizumab for non-small cell lung cancer experienced progressive fatigue, intractable nausea and reduced mobility since commencing her cancer treatment. After repeat admissions and prolonged inpatient stay from compounded septicaemia, a diagnosis of programmed cell death 1 (PD-1) inhibitor-induced hypophysitis was confirmed, with remarkable improvement on commencement of cortisol replacement.While this side effect is known to oncologists, the non-specific symptoms and a lack of familiarity with PD-1 inhibitor and programmed cell death ligand 1 inhibitor therapies in other medical fields can result in diagnostic delays if not actively searching for hypophysitis.Intractable nausea, vomiting and weight loss, even in the absence of hyponatraemia or hypoglycaemia, should trigger physicians to consider hypophysitis.
Creutzfeldt-Jakob disease mimicking limbic encephalitis as a cause of rapid neurological deterioration
Authors: Rajasingam Vinod , Craig Donald P Peter , Hwang Yun , Satgunaseelan Laveniya , Buckland Michael , Tomazini Martins Rodrigo 
Published: February 2025

BackgroundA broad range of inflammatory and neurodegenerative conditions manifest with progressive cognitive and behavioural changes. A diagnostic challenge is the differentiation of limbic encephalitis (LE) from Creutzfeldt-Jakob disease (CJD). LE and CJD are distinct neurological conditions with distinct variations in their clinical course, with overlapping clinical presentations. LE can be subdivided into autoimmune paraneoplastic and non-paraneoplastic subtypes, under the umbrella of autoimmune LE. CJD is the most prevalent form of human prion disease and the subtype sporadic CJD (sCJD) the most common.Case presentationThis case study presents a 68-year-old man with a 6-week history of progressive cognitive decline and behavioural changes, ultimately leading to a dire clinical state. The initial symptoms included confusion, intermittent headaches and episodes of aggression towards his wife, preceded by 2 weeks of visual hallucinations. On examination, the patient displayed an ataxic gait, with signs of cerebellar dysfunction. The clinical course evolved, marked by myoclonic jerks, culminating in a decline in both his Glasgow Coma Scale (GCS) score and overall clinical status.ConclusionThe patient’s rapidly deteriorating condition over 6 weeks was thought to be too rapid for sCJD, and the patient was treated initially as an LS. However, post-mortem biopsy findings confirmed CJD. Asymmetric periodic discharges on EEG, asymmetric neuroimaging changes and the manifestation of psychiatric symptoms should not preclude the diagnosis of sCJD. This case highlights the importance of recognising the potential rapid deterioration of sCJD, which would alert clinicians to earlier diagnosis and management.
Prevalence and proposed aetiologies of dystonias or yips in athletes playing overhand sports: a scoping review protocol
Authors: Knox Jordan , Shah Karishma , McFarland Mary M , Casucci Tallie , Jones Kyle Bradford 
Published: February 2025

IntroductionSports-related dystonia, also called the yips, are often seen in athletes in multiple sports. In this condition, an athlete abruptly loses the ability to perform a repetitive motion performed thousands of times. Such occurrences are often assumed to be psychological in nature, and thus evaluation for other causes is often lacking. All reviews on the topic have failed to focus on athletes in overhand sports. This scoping review will evaluate the available evidence regarding upper extremity focal dystonias (yips) in athletes participating in overhand sports in any worldwide clinical or sport setting.Methods and analysisWe will conduct our scoping review with guidance from the latest version of the Joanna Briggs Institute’s (JBI) Manual for Evidence Synthesis, a widely accepted methodology for conducting reviews. We organised our research question and inclusion criteria to the JBI’s mnemonic; Participants: athletes that participate in overhand sports; Concept: upper extremity focal dystonias or yips; and Context: any worldwide clinical or sports setting. Search results were retrieved on 26–27 June 2024, in the following databases: MEDLINE (Ovid) 1946–2024, SPORTDiscus (EBSCOhost) 1800–2024, APA PsycINFO (EBSCOhost) 1872–2024, Embase (Elsevier) 1974–2024, Web of Science Core Collection (Clarivate) 1900–2024, Sports Medicine & Education Index (ProQuest) 1970–2024 and Dissertations and Theses Global (ProQuest) 1861–2024. Using Covidence, two reviewers from a team of three will independently screen titles and abstracts, screen full text articles for inclusion, and independently extract data from our included studies. Results will be presented as a narrative descriptive analysis along with tabular data on the prevalence, diagnostic criteria and treatment for yips in athletes of overhand sports.Ethics and disseminationAs this describes a scoping protocol, ethical approval is not necessary. Review findings will be submitted to peer-reviewed publications and presentations at local and national conferences.Trial registration numberThis protocol is registered with the Open Science Framework.
Protocol for a randomised controlled trial of a weight maintenance intervention to promote fat loss in pregnant individuals with obesity
Authors: Redman Leanne M , Phelan Suzanne , Apolzan John W , Beyl Robbie A , Altazan Abby D , Dickey Madison S , Simeon Emerson , Flanagan Emily W , Cabre Hannah E , Sparks Joshua R , Kebbe Maryam , Caughey Aaron B , Valent Amy M , Hsia Daniel S , Yin Elaine , Keadle Sarah K 
Published: February 2025

IntroductionIn pregnancy, people with obesity or excess adiposity are prone to excess gestational weight gain (GWG) and have the highest risks for multiple maternal morbidities. Epidemiological studies suggest that the lowest incidence of adverse maternal and infant outcomes occurs with GWG lower than current recommendations (<5 kg) and with gestational weight maintenance, resulting in fat mass loss, in those with obesity. Data from randomised clinical trials are needed to evaluate the efficacy of a fat mass loss intervention on pregnancy outcomes. The objective of this proof-of-principle randomised controlled trial is to test the effect of a gestational fat mass loss intervention in pregnant individuals with obesity on changes in weight, fat mass and cardiometabolic disease risk factors.Methods and analysisIn this two-site randomised parallel group, 100 women (30% black; 30% Hispanic) with pre-existing obesity (31.0≤body mass index≤55.0 kg/m2) are randomised to usual care (Provider Directed Group) or usual care plus a fat mass loss intervention with food provision (Weight Maintenance Group). The primary outcomes of the trial (Healthy Mamas/Mamis Saludables) are weight, fat mass (via three-compartment model) and cardiometabolic disease risk factors (ie, blood pressure, lipids, glucose, insulin) from baseline (~13 weeks gestation) to ~35 weeks gestation and at 2 weeks postpartum. Secondary aims evaluate the safety of the fat mass loss intervention during pregnancy and test the hypotheses that compared with usual care, the intervention will have no significant adverse effect on fetal growth, neonatal size, infant body composition and other adverse events. Mediators (eg, eating, activity) and moderators (eg, parity, obesity grade, race/ethnicity) of intervention effects are also examined. Finally, the study will explore the effect of prenatal fat mass loss on reducing the incidence of adverse obstetrical outcomes, including non-elective caesarean delivery, gestational diabetes, hypertension and pre-eclampsia.Ethics and disseminationThe trial has been approved by the Pennington Biomedical Research Center Institutional Review Board, is monitored by an independent data and safety monitoring board and will be conducted in agreement with the Declaration of Helsinki. All results, positive, negative and inconclusive, will be disseminated at national and/or international scientific meetings and in peer-reviewed scientific journals.Trial registration numberNCT04731688.
Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation
Authors: Liu Cuiying , Guo Jiayi , Guan Longfei , Li Junfa , Xu Baohui , Zhao Heng 
Published: February 2025

BackgroundMelatonin protects against ischaemic stroke in diabetic animal models, though the mechanisms involving brain and peripheral immune responses remain underexplored. We aimed to clarify how melatonin interacts with these immune responses to protect against stroke in diabetic mice.MethodsType 1 diabetes mellitus (T1DM) was induced in mice using streptozotocin. RNA sequencing of brain tissue and peripheral blood mononuclear cells (PBMCs) was performed 24 hours poststroke. Inflammatory responses were evaluated 72 hours after ischaemia/reperfusion.ResultsMelatonin reduced infarction and improved neurological function in T1DM mice. In the ischaemic brain, melatonin downregulated inflammatory factor expression, with bioinformatics identifying 62 differentially expressed genes (DEGs) related to inflammation and 11 associated with inflammasomes. Western blotting confirmed reductions in NLRP3, HMGB1 and Cleaved Caspase-1 expression. Flow cytometry showed reduced infiltration of CD8+T cells and neutrophils. Melatonin decreased IL-6, IL-1β and IL-4 levels. In PBMCs, RNA sequencing revealed 939 DEGs following melatonin treatment. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that downregulated DEGs were involved in metabolic pathways, and upregulated DEGs were enriched in the Jak-STAT signalling pathway. GO analysis showed that downregulated DEGs were enriched in the cytosol, and upregulated DEGs related to macromolecule modification. Protein–protein interaction analysis revealed that melatonin affected 38 inflammation-associated genes linked to key cytokines (Il6, Il1b, Ifng, Il4). Flow cytometry indicated melatonin increased CD8+T cells, monocytes and neutrophils in the blood, suggesting a reversal of immunosuppression. Multiplex cytokine assays showed melatonin decreased IL-6 and IFN-γ levels.ConclusionPoststroke melatonin therapy reduces ischaemic brain damage in T1DM mice by modulating central and peripheral inflammatory responses.
EXPLORING THE IMPACT OF DYNAMIC MANAGERIAL CAPABILITIES ON INNOVATION: A TYPOLOGY-BASED APPROACH
Authors: GHAVAMIPOUR MOHSEN , BOOSHEHRI ALIREZA , TAVAKOLI GHOLAMREZA 
Published: February 2025

This study examines the interplay between Dynamic Managerial Capabilities (DMCs) and innovation performance in Iran’s industrial sector. We propose a novel framework that categorises managers based on three DMC components — managerial human capital, social capital, and cognitive capabilities — and investigates their combined effects on innovation. Using a sample of 344 managers, data were analysed through Structural Equation Modeling (SEM) and Analysis of Variance (ANOVA). Findings reveal that specific DMC profiles, particularly those that align with the firm’s strategic context, significantly enhance innovation outcomes. The results underscore the importance of tailored managerial development strategies in fostering innovation within dynamic and complex environments. This study contributes to the strategic management literature by offering practical insights for optimising organisational performance through the strategic configuration of managerial capabilities.
Case 338
Authors: Shah Amar , Zulfiqar Maria 
Published: February 2025

History A 25-year-old female patient presented to the emergency department with worsening abdominal discomfort over the past 2–3 months. The patient had not experienced fever, chills, or dysuria. Past medical history was notable for two completed pregnancies; otherwise, there was no pertinent medical history or family history. At physical examination, the patient was uncomfortable but not in acute distress. There was tenderness to palpation in the right upper quadrant and epigastric region, but no rebound tenderness or guarding. Vital signs were blood pressure of 141/85 mm Hg, pulse rate of 91/min, and temperature of 37.2 °C. The serum β–human chorionic gonadotropin test result was negative for pregnancy, and urinalysis showed no leukocyte esterase or nitrites. Routine blood investigations, including white blood cell count, were within normal limits. Initial evaluation with contrast-enhanced CT of the abdomen and pelvis was performed ( Fig 1 ), followed by MRI of the abdomen without and with intravenous contrast material ( Fig 2 ).