bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of an invasive, hyper-aerotolerant
Campylobacter jejuni
strain causing bacteremia in a pediatric leukemia patient
Authors: Zeng Ximin , Lloyd Kevin M. , Hamdy Rana F. , Shapiro Craig A. , Fisher Mark A. , Lin Jun , Liu Benjamin M. 
Published: February 2025

ABSTRACT

Background

Campylobacter jejuni
is a leading pathogen causing gastroenteritis in humans. Invasive
C. jejuni
strains crossing the gut-blood barrier can cause bacteremia. Despite its microaerophilicity (preferring <5% O
2
atmosphere), hyper-aerotolerant (HAT)
C. jejuni
has recently been isolated from intestines in poultry and humans. Elevated aerotolerance may enhance
C. jejuni
survival in the ecosystem, thereby promoting its transmission. However, invasive HAT isolates of
C. jejuni
have not been reported in bacteremia in humans.

Case Summary

A
C. jejuni
strain (CNH-HAT-1) was isolated from a 7% CO
2
(~16% O
2
) atmosphere subculture of an aerobic blood culture from a 5-year-old boy with B-cell acute lymphoblastic leukemia presenting with bloody stool, fever, and neutropenia. The organism identification was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S-rRNA sequencing. HAT phenotype of this isolate was confirmed by aerotolerance testing. Belonging to the ST-21 clonal complex, CNH-HAT-1 is phylogenetically close to recently reported invasive
C. jejuni
sheep abortion strains and some bacteremia-associated strains. CNH-HAT-1 possesses a CJIE-1 prophage element, a functional enterobactin receptor CfrB, and G250A mutation in the major outer-membrane protein PorA, which likely contributes to
C. jejuni
invasiveness. CNH-HAT-1 is resistant to penicillins/cephalosporins but susceptible to aminoglycosides, fluoroquinolones, and macrolides. The patient improved with intravenous gentamicin, followed by enteral therapy with azithromycin.

Conclusion

We identified a novel invasive bloodstream
C. jejuni
strain proven
in vitro
to be HAT, shedding light on key genomic features linking with its pathogenesis. Given its enhanced survival of HAT
C. jejuni
in ecosystem, a clinical microbiology lab should be vigilant with detecting them from blood cultures.
Use of gastrointestinal syndromic multiplex molecular assays and detection of
Escherichia coli
pathotypes in pediatric wards
Authors: Bizot Etienne , Bonacorsi Stéphane , Labé Pauline , Pinhas Yael , Cointe Aurélie , Ferroni Agnès , Cohen Jérémie F. , Lécuyer Hervé , Toubiana Julie 
Published: February 2025

ABSTRACT

Escherichia coli
pathotypes are enteric pathogens detected in gastrointestinal multiplex polymerase chain reaction (mPCR), with controversial clinical relevance. Our study aimed to describe clinical features and therapeutic decisions associated with
E. coli
detections in gastrointestinal mPCR. Children with positive mPCR for enteroaggregative (EAEC)
,
enteropathogenic (EPEC)
,
enterotoxigenic (ETEC), Shiga toxin-producing
E. coli
(STEC), and enteroinvasive
E. coli
(EIEC)/
Shigella
identified in two pediatric hospitals over 18 months (2020–2021) were included. We described the frequency of
E. coli
detection and subsequent modifications in antibiotic strategies. Among the 2,471 mPCRs performed, 338 (14%) tested positive for at least one
E. coli
pathotype. The patient's mean age was 4.2 years, with 95% experiencing gastrointestinal symptoms. Clinical presentation was generally comparable between
E. coli
pathotypes. A recent travel abroad was reported in 68/338 (20%) cases and was mainly observed in EIEC/
Shigella
infections. An
E. coli
was detected alone in 177/338 (52%) cases and with another virus, bacteria, or parasite in 161 (48%) cases. Multiple enteric pathogens were mainly detected with ETEC (
n
= 24/26, 92%) and EAEC (
n
= 82/121, 68%) detections. Antibiotic therapy was prescribed in 136/338 (40%) cases, with initiation based on mPCR results in 69/338 (20%). No antibiotic therapy was discontinued following positive mPCR results. Among the 69 initiations, 31 were deemed inappropriate after retrospective chart review.
E. coli
detection with mPCR tests may lead to inappropriate antibiotic initiation. Caution is advised when interpreting results from gastrointestinal mPCRs in children, as clinicians may be unaware of their often unclear or irrelevant clinical significance.

IMPORTANCE

Escherichia coli
pathotypes are increasingly detected through the widely used syndromic gastrointestinal multiplex PCR panels. However, their clinical significance and impact on antibiotic therapy in children remain uncertain. This study describes the clinical and microbiological characteristics associated with
E. coli
detections, as well as the subsequent modifications in antibiotic strategies. It highlights the frequent detection of
E. coli
pathotypes, often in association with other enteric pathogens, and reveals that nearly half of the antibiotics prescribed following these results were deemed inappropriate. These results underscore the need to enhance clinicians' interpretation of
E. coli
-positive results and reassess treatment strategies to optimize patient care.
Cell differentiation controls iron assimilation in the choanoflagellate
Salpingoeca rosetta
Authors: Leon Fredrick , Espinoza-Esparza Jesus M. , Deng Vicki , Coyle Maxwell C. , Espinoza Sarah , Booth David S. 
Published: February 2025

ABSTRACT

Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate
Salpingoeca rosetta
endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that
S. rosetta
can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (
cytb561a
). This gene and its mammalian ortholog, the duodenal cytochrome b561 (
DCYTB
) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.

IMPORTANCE

This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate,
S. rosetta
, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that
S. rosetta
has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.
Detection of mpox and other orthopoxviruses using a lateral flow device as a point-of-care diagnostic
Authors: Laidlaw Stephen M. , Ulaeto David , Lonsdale Steve , Clark Graeme , Sumner Rebecca , Edwards Thomas , Adams Emily , Logist Anne-Sophie , Van Holm Bram , Maluquer de Motes Carlos , Horby Peter , Maes Piet , Carroll Miles W. 
Published: February 2025

ABSTRACT

In 2022, the World Health Organization declared the worldwide outbreak of mpox to be a public health emergency of international concern. The causative monkeypox virus (MPXV) belonged to clade IIb and is transmitted through sexual contact with a low case fatality rate (0.1%), which, together with under-detection, all contributed to a rapid global spread particularly within the MSM (men who have sex with men) community. As MPXV clade II remains circulating worldwide, a new outbreak of the more fatal clade I disease has been declared in Central and East Africa, and remains uncontrolled in part due to the lack of point-of-care (POC) diagnostics for rapid decisions on treatment and self-isolation. To address the lack of POC solutions for mpox, we have designed and evaluated an orthopoxvirus-specific lateral flow device (LFD) that could be used for the diagnosis of mpox. Using an LFD comprising four monoclonal antibodies against the A27 protein, we demonstrate sensitivity to 3 × 10
5
pfu/mL. This sensitivity is expected to be sufficient for the detection of MPXV from lesion sites and may also be sufficient for other sample types such as saliva and urine. We found that the presence of guanidinium thiocyanate, a common ingredient in inactivating viral transport media, masked the LFD antigen, resulting in false negatives. POC diagnosis of mpox may be possible using an LFD to reduce delays arising from sample shipment to centralized laboratory testing facilities. In order to achieve this, our work demonstrates that an LFD-optimized buffer is required, as the sample collection buffer may have a detrimental impact on sensitivity for clinical material.

IMPORTANCE
Mpox cases have dramatically increased both in traditionally monkeypox virus endemic countries and also worldwide. This increase comes at a time when immunity derived from smallpox vaccination is no longer available. Diagnosis of mpox is complicated due to both disease presentation and the availability of local diagnostic laboratories. The availability of a point-of-care diagnostic tool such as an lateral flow device (LFD) would play an important role to both diagnose and prevent onward transmission. This manuscript provides developers and assessors with key data for defining true sensitivity and specificity of a successful LFD in addition to buffer conditions for sample collection.
Comparative effectiveness and prescribing trends of modified release versus immediate release indapamide in patients with hypertension: cohort study
Authors: Yan Vincent Ka Chun , Ju Chengsheng , MacDonald Thomas MacLennan , Mackenzie Isla S , Flynn Robert , Williams Bryan , Chen Yang , Chan Esther W , George Jacob , Wei Li 
Published: February 2025

Objective
To investigate the prescribing trends of indapamide, a thiazide-like diuretic, and the long term comparative effectiveness of modified release versus immediate release indapamide.

Design
Cohort study.

Setting
IQVIA Medical Research Data UK database, incorporating data from The Health Improvement Network database, 1 January 2005 to 31 December 2020.

Participants
Of 1 904 289 patients with hypertension, 86 388 started indapamide treatment during the study period. 30 021 patients received modified release and 56 367 immediate release indapamide.

Main outcome measures
Monthly prescribing trends of modified release and immediate release indapamide are described. A pragmatic trial was emulated to compare the five year risks of composite cardiovascular events (myocardial infarction and stroke) and death between modified release and immediate release indapamide. Intention-to-treat and per protocol effects of treatment were estimated with pooled logistic regression models. Confounding and selection bias were accounted for by multivariable adjustments and inverse probability weights.

Results
1 38 414 patients who used indapamide were identified among 1 904 289 patients with hypertension. A greater increase was seen in the proportion of users of immediate release indapamide (from 0.43% in 2005 to 2.31% in 2020) than in users of modified release indapamide (from 0.71% to 0.79%). 86 388 patients (30 021 and 56 367 who started modified release and immediate release indapamide, respectively) were eligible for the trial emulation. In the intention-to-treat analysis, no difference was found in the risk of cardiovascular events (hazard ratio 0.99, 95% confidence interval (CI) 0.90 to 1.08) or death (hazard ratio 0.97, 0.92 to 1.02) between modified release and immediate release indapamide. In the per protocol analysis, a lower risk of cardiovascular events was found with modified release indapamide than with immediate release indapamide (risk difference −0.39%, 95% CI −0.71% to −0.06%; hazard ratio 0.81, 95% CI 0.68 to 0.98), which was mainly driven by myocardial infarction (risk difference −0.36%, 95% CI −0.64% to −0.08%; hazard ratio 0.80, 95% CI 0.64 to 1.01). Similar risks of death (hazard ratio 1.03, 95% CI 0.90 to 1.17) were found for the two formulations.

Conclusions
In patients treated with indapamide for hypertension, starting treatment with modified release or immediate release indapamide had similar risks for cardiovascular events or all cause mortality. In an exploratory secondary analysis, sustained treatment with modified release preparations was associated with a lower the risk of cardiovascular events but not all cause mortality compared with immediate release preparations. These findings need to be confirmed in prospective studies.
Whole-body integral dose and post-radiotherapy lymphocytopaenia in solid tumours
Authors: Joseph Nuradh , Alagiyawanna Lanka , Ruwanpura Thilina , Gunasekera Sanjeeva , Ruvinda Lakitha , Madushan Sampath , Choudhury Ananya 
Published: February 2025

ObjectiveSince modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) pivot on a strategy of dose redistribution, it may increase integral dose and consequently worsening of lymphocytopaenia. In this study, our objective was twofold: first to validate the correlation between integral body dose and post-treatment lymphocytopaenia in a cohort of patients treated with curative-intent radiotherapy and second to validate its prognostic impact.Methods and analysisPatients treated with curative intent radiotherapy with complete blood counts were included in the study. Data on the following variables were collected: treatment site, prescribed dose, use of concurrent chemotherapy, mean body dose, mean body volume, treatment technique and disease-free survival.ResultsA total of 116 patients were included for analysis. There was a significant decline in lymphocyte counts after radiotherapy (2.2×109/L vs 0.8×109/L; p<0.001). Multivariate linear regression analysis of post-treatment lymphocytopaenia revealed a significant correlation with pretreatment lymphocyte counts, integral body dose, use of IMRT and use of concurrent radiosensitising chemotherapy. Univariate survival analysis was performed in 37 patients with squamous cell carcinoma of the head and neck. In the Cox proportional hazards model, post-treatment lymphocyte count was statistically significant as a continuous variable (Hazard Ratio=0.998, p=0.01) and as a dichotomous variable.ConclusionThe negative correlation between integral body dose and post-treatment lymphocytopaenia was validated, and post-treatment lymphocytopaenia is an adverse prognostic factor in patients with head and neck cancer treated with curative-intent radiotherapy.
Evaluating the implementation of inclisiran in primary care: process evaluation interim findings from interviews with key stakeholders
Authors: Wilson Paul , Elvey Rebecca , Mathieson Amy , Bower Peter , Gibson Martin , Vell Tracey , Dixon Samantha 
Published: February 2025

ObjectivesVICTORION-Spirit was a hybrid study designed to assess the feasibility of implementing inclisiran, a novel cholesterol-lowering treatment and behavioural support within primary care centres in England. This process evaluation aimed to evaluate the implementation of inclisiran for patients with elevated low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents (n=900), from the perspectives of key stakeholders.DesignVICTORION-Spirit was a phase IIIb, multicentre, randomised, controlled study. We followed a process evaluation strategy to collate the views of stakeholders via semistructured interviews and to gain insights on the ‘implementability’ of inclisiran in primary care. Data were generated via interviews with patients, healthcare providers and research nurses and analysed using a qualitative rapid analysis approach.SettingPrimary care in Greater Manchester, UK.Participants84 participants were interviewed, including patients (n=56), professionals at participating practices in VICTORION-Spirit (n=13), health advisors (n=4) and research nurses (n=11).ResultsInterim findings suggest the process of receiving and providing inclisiran during the study was ‘straightforward’, and the behavioural support provided to some patients was generally viewed favourably. Beyond the trial, patients and healthcare providers thought the delivery of inclisiran could work well as a practice nurse-provided service. Barriers to implementing inclisiran were generally related to workforce and workload pressures in primary care, and an incentive structure to support delivery was recommended.ConclusionsPatients and healthcare providers supported implementing inclisiran in primary care. It was convenient for patients to receive inclisiran in general practice, and most providers felt that the intervention was a useful addition to existing lipid-lowering treatments. Several barriers to implementation were highlighted, including concerns relating to general practice resources and costs.Trial registration numberNCT04807400.
Predicting the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis using a stacked ensemble machine learning model: a retrospective study based on the MIMIC database
Authors: Li Fuyuan , Wang Zhanjin , Bian Ruiling , Xue Zhangtuo , Cai Junjie , Zhou Ying , Wang Zhan 
Published: February 2025

ObjectiveThis study developed and validated a stacked ensemble machine learning model to predict the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis.DesignA retrospective study based on patient data from public databases.ParticipantsThis study analysed 1295 patients with acute pancreatitis complicated by septicaemia from the US Intensive Care Database.MethodsFrom the MIMIC database, data of patients with acute pancreatitis and sepsis were obtained to construct machine learning models, which were internally and externally validated. The Boruta algorithm was used to select variables. Then, eight machine learning algorithms were used to construct prediction models for acute kidney injury (AKI) occurrence in intensive care unit (ICU) patients. A new stacked ensemble model was developed using the Stacking ensemble method. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, accuracy, recall and F1 score. The Shapley additive explanation (SHAP) method was used to explain the models.Main outcome measuresAKI in patients with acute pancreatitis complicated by sepsis.ResultsThe final study included 1295 patients with acute pancreatitis complicated by sepsis, among whom 893 cases (68.9%) developed acute kidney injury. We established eight base models, including Logit, SVM, CatBoost, RF, XGBoost, LightGBM, AdaBoost and MLP, as well as a stacked ensemble model called Multimodel. Among all models, Multimodel had an AUC value of 0.853 (95% CI: 0.792 to 0.896) in the internal validation dataset and 0.802 (95% CI: 0.732 to 0.861) in the external validation dataset. This model demonstrated the best predictive performance in terms of discrimination and clinical application.ConclusionThe stack ensemble model developed by us achieved AUC values of 0.853 and 0.802 in internal and external validation cohorts respectively and also demonstrated excellent performance in other metrics. It serves as a reliable tool for predicting AKI in patients with acute pancreatitis complicated by sepsis.
Developing evaluation metrics to measure the US national institute of health plans to enhance diverse perspectives: a protocol for a consensus-based study
Authors: Levites Strekalova Yulia A , Jain Sanjay , Sarder Pinaki 
Published: February 2025

IntroductionThe diversity of participating investigators representing diverse disciplines, career stages, stakeholder groups, regions and types of institutions is essential for the success of large-scale research programmes. In 2021, the National Institutes of Health introduced a requirement for some of its large grants to include a separate section that describes the project’s plan for enhancing diverse perspectives (PEDPs). Our project aims to develop consensus-based PEDP evaluation metrics and instruments that can be systematically and sustainably collected across the projects.Methods and analysisEvaluation work is organised into three objectives. First, shared knowledge about PEDP infrastructures, activities and outcomes will be elicited through the review of the PEDP texts of funded projects, with 15 as the target sample size. Data will be analysed using a cultural domain analysis approach and assessed for recurrence and salience of PEDP metrics. Second, consensus-based evaluation metrics will be developed using a three-round Delphi method. The descriptive statistics (mean, SD and IQR) and cultural consensus analyses will be applied to the first and last rounds of the Delphi survey. Third, metrics will be piloted for implementation and validation within one of the Human BioMolecular Atlas Programme sites. Work will be completed by Fall 2025.Ethics and disseminationThe long-term goal of the effort reported in this paper is to develop PEDP common metrics that are generalisable and feasible across diverse projects. This rigorous, focused evaluation development effort aims to inform scientific practices and policies around implementing the plans to enhance diverse perspectives.