bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health outcomes and drug utilisation in children with Noonan syndrome: a European cohort study
Authors: Santoro Michele , Barisic Ingeborg , Coi Alessio , Tan Joachim , Garne Ester , Loane Maria , Odak Ljubica , Abate Maria Valentina , Ballardini Elisa , Cavero-Carbonell Clara , Gatt Miriam , Gissler Mika , Klungsøyr Kari , Lelong Nathalie , Tucker David , Wellesley Diana , Morris Joan K. 
Published: February 2025

Abstract

Background
Noonan Syndrome (NS) is a rare multisystemic disorder with heterogeneous phenotypic manifestations. The aim of this study was to analyse rates of survival, hospitalisation, surgeries and prescriptions in children born with NS in the first 10 years of life.

Methods
This is a multi-centre population-based cohort study. Data on 175 liveborn children diagnosed with NS from 11 EUROCAT congenital anomaly registries were linked to healthcare databases. Each registry applied a common data model to standardise data and run common syntax scripts to produce aggregated results which were pooled using random effects meta-analyses.

Results
Mortality rates were high in the first year of life with 5.4% (95%CI 1.5%-10.1%) of children dying before the age of 1 year with a further 2% dying up to age 5. In the first year, 87.9% (95%CI 75.3%-94.3%) of children were hospitalized and the median Length Of hospital Stay (LOS) was 15.3 days (95%CI 9.3–21.2). After the first year, the proportion of children hospitalized remained higher than 70%, but the LOS decreased to 1.3 days per year. In the first 5 years, 65.2% of children underwent a median of two surgical procedures. The median age at first surgery was 29 weeks. The proportion of children with an antibiotic prescription increased from 53.6% at age 1 to 62.4% yearly until 4 years of age.

Conclusions
Children with NS have high mortality and morbidity not only in the first year of life but also up to five years of age. This study evaluated the health burden of NS and provided information for clinicians, health-care providers and families.
Sympatric non-biting flies serve as potential vectors of zoonotic protozoan parasites on pig farms in China
Authors: Liu Yufeng , Dhakal Pitambar , Hou Wenyan , Shan Fa , Wang Nanhao , Yang Bin , Qin Huikai , Li Xiaoying , Wang Rongjun , Zhang Longxian , Zhang Sumei , Li Junqiang 
Published: February 2025

Abstract

Background

Cryptosporidium spp., Enterocytozoon bieneusi, and Blastocystis sp. are common enteric parasites in humans and pigs. Ascertaining whether non-biting flies (NBFs) serve as potential vectors of these parasites on pig farms is a crucial aspect of disease control.

Methods
Non-biting flies were collected and identified by morphology analysis together with sequence analysis of the mitochondrial cytochrome c oxidase I (CO1) gene as confirmation. In a cross-sectional study, the small-subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium spp., the internal transcribed spacer region (ITS) region of E. bieneusi and the SSU rRNA gene of Blastocystis sp. were investigated in fresh pig fecal samples and sympatric NBFs.

Results
The results revealed the occurrence of five species of NBFs (Musca domestica, 91.2%; Lucilia sericata, 5.8%; Chrysomya megacephala, 1.7%; Aldrichina grahami, 0.6%; Helicophagella melanura, 0.6%) in the collected pig fecal samples. The prevalence of Cryptosporidium spp., E. bieneusi and Blastocystis sp. on the body surface of NBFs was 0.6% (2/342), 4.4% (15/342) and 20.8% (71/342), respectively. Similarly, the prevalence of these parasites in the lysates of NBFs (= in vivo carriage) was 0% (0/342), 2.7% (9/342) and 10.5% (36/342), respectively. The prevalence of Cryptosporidium spp., E. bieneusi and Blastocystis sp. in pigs from which fly samples were collected was 2.3% (41/1794), 12.6% (226/1794) and 30.8% (553/1794), respectively. The zoonotic Cryposporidium suis/C. scrofarum, E. bieneusi ITS genotypes EbpA/EbpC and Blastocystis sp. subtypes ST1/ST3/ST5 were identified in both NBFs and pig feces. NBFs were found to carry E. bieneusi and Blastocystis sp. on their body surface as well as in the lysates.

Conclusions
These findings demonstrate the role of NBFs as potential vectors in the dissemination of these zoonotic parasites in pig farms, and also highlight the possibility of their transmission to humans.

Graphical Abstract
BBSome deficiency in Lotmaria passim reveals divergent functions in trypanosomatid parasites
Authors: Yuan Xuye , Kadowaki Tatsuhiko 
Published: February 2025

Abstract

Background
The BBSome is an octameric protein complex crucial for ciliary transport, though it also participates in multiple other cellular processes. These diverse functions may result from the co-option of its ancestral roles. Studying the BBSome in flagellated protists can provide insights into these ancestral functions and their subsequent adaptations.

Methods
We examined the functions of the BBSome (LpBBS1 and LpBBS2) in Lotmaria passim, a monoxenous trypanosomatid parasite infecting honey bees. The phenotypes resulting from depletion of LpBBS1 using the auxin-inducible degron system and disruption of LpBBS2 were characterized.

Results
Parasites deficient in LpBBS2 are smaller and less motile compared with wild-type. Although intraflagellar transport of a marker membrane protein is only mildly impaired, its association with lipid rafts is significantly disrupted in the mutants. This suggests that the BBSome is essential for maintaining lipid raft integrity in L. passim. Transcriptomic comparisons between wild-type and LpBBS2-deficient parasites reveal that the BBSome may also influence processes related to metabolism, membrane localization of specific proteins, DNA repair, microtubules, and mitochondria.

Conclusions
In contrast to Leishmania mexicana, the BBSome in L. passim is crucial for efficient infection of the honey bee gut, demonstrating that its cellular functions vary between related trypanosomatid species. The BBSome is likely an adaptor that links multiple proteins in a species-specific manner under various cellular contexts.

Graphical Abstract
Broad consent in the emergency department: a cross sectional study
Authors: Fischer-Rosinský Antje , Eienbröker Larissa , Möckel Martin , Hanses Frank , Hans Felix Patricius , Wolfrum Sebastian , Drepper Johannes , Heinrich Philipp , Slagman Anna 
Published: February 2025

Abstract

Background
The Medical Informatics Initiative (MII) introduced a broad consent form (MII-BC) encompassing clinical, insurance, and biomaterial data, along with re-contacting options. In the emergency department (ED), outpatient and inpatient patients of all illnesses and severity could be reached early in their treatment course. The BC-ED (Broad Consent in the Emergency Department) project uniquely investigated the implementation of MII-BC in EDs, exploring feasibility, selection bias and patients’ perceptions of voluntariness, information recall, motivation, and satisfaction.

Methods
The BC-ED project involving four university hospital EDs in Germany, is part of CODEX+ (Collaborative Data Exchange and Usage), an initiative within the Network University Medicine (NUM). To minimize selection bias, a systematic sampling approach (every 5th/30th patient) was applied, with patient recruitment and consent processes adapted to local conditions and therefore varying among sites. Data collection included patient questionnaires, surveys completed by study nurses, and routine clinical data. Analysis was conducted descriptively using SPSS.

Results
Of 1,138 patients approached, 553 (48.6%) were capable of giving consent. Of 353 patients who could not consent, primary reasons included language barriers (35.4%) and inability to grasp study details (21.5%). Of all eligible patients, 3.3% could not be contacted. Of 535 (47.0%) patients able to consent and contacted, 313 consented to the MII-BC. Resulting in a consent rate of 27.5% corresponding to the baseline population and 58.5% of those contacted. Motivations for consenting were general support for research (85.3%) and the desire to help future patients (78.2%). Patients generally reported a high level of understanding and satisfaction with the consent process, reporting comprehensive understanding of scientific data use (89.8%) and associated risks (82.2%). However, discrepancies were noted between consented options and patient recall.

Conclusions
This study is the first to investigate the implementation of the MII-BC in the challenging ED environment. With a consent rate of 27.5% total baseline population and 58.5% of those contacted, it demonstrates that patients were able and willing to participate in research. Reasons for non-consent were barriers like language and medical conditions. Strategies to address these barriers are crucial for inclusivity. Although patients generally understood the consent process, discrepancies in recall highlight the need for improved comprehension strategies.

Trial registration
German Clinical Trials Register on 25 October 2022 (DRKS0003054).
Quality of life in persons at risk for bipolar disorder: a two year prospective-longitudinal observational cohort study (BipoLife)
Authors: Glaus Johanna , Karow Anne , Lambert Martin , Sowada Pia , Bröckel-Bundt Kyra , Berndt Christina , Sauer Cathrin , Juckel Georg , Fallgatter Andreas J. , Bechdolf Andreas , Reif Andreas , Matura Silke , Kittel-Schneider Sarah , Stamm Thomas , Kircher Tilo , Falkenberg Irina , Jansen Andreas , Correll Christoph U. , Fusar-Poli Paolo , Bauer Michael , Pfennig Andrea , Rohenkohl Anja Christine 
Published: February 2025

Abstract

Background
Improving quality of life (QoL) is important for the treatment of people with bipolar disorder (BD). Early-BipoLife is a German multicentre naturalistic, prospective-longitudinal observational cohort study investigating early recognition and intervention in people at increased risk of developing a BD. This analysis aims to investigate influencing factors and changes in QoL as a basis for the development of early intervention strategies in patients with at risk syndrome for BD.

Method
A cohort of 1086 participants (15–35 years) with at least one risk factor (EPIbipolar criteria) for BD was assessed over the course of 2 years. Changes in QoL (WHOQOL-BREF) were evaluated in a mixed model for repeated measures.

Results
Compared to an age-matched comparison group, people at risk for BD showed significant lower QoL in all domains at baseline. The overall QoL of the psychological well-being domain of the WHOQOL-BREF increased over the 2 year study course (p < 0.001). The bipolar risk group (EPIbipolar) change from baseline divided into (a) decreasing, (b) increasing and (c) constant risk group in the course of 2 years. Baseline risk group assignment was not a significant predictor of change in QoL over 2 years for any of the QoL domains, but participants with an increase in risk over the 2-year course had a significantly smaller gain in QoL than the group with constant risk (p = 0.014) or decreasing risk (p < 0.001). Higher levels of QoL were associated with a higher self-rated ability to use coping strategies. Moreover, a higher level of functioning (GAF) at baseline was positively correlated with improvement of different QoL domains after 2 years.

Conclusion
Patients with a risk syndrome for BD reported significantly reduced QoL compared to their age-matched comparison group. Risk status monitoring might be beneficial to identify individuals who could profit from an intervention to increase their QoL. Further studies promoting the development of coping strategies for successful self-management could be helpful to improve overall mental health and positively influence QoL.
Intraindividual crossover comparison of gadobenate dimeglumine-enhanced and gadoxetate disodium-enhanced MRI for characterizing focal liver lesions
Authors: Tang Wenjie , Xiao Yuanqiang , Kuang Sichi , Rong Dailin , He Bingjun , Grazioli Luigi , Hussain Shahid M. , Wang Jin 
Published: February 2025

Abstract

Background
Gadobenate and gadoxetate are hepatobiliary magnetic resonance imaging (MRI) contrast agents. We intraindividually compared these two agents for the characterization of focal liver lesions (FLLs).

Methods
A total of 140 adult subjects were randomized to undergo two 3-T MRI exams separated by 7–14 days, one with 0.05 mmol/kg gadobenate and one with 0.025 mmol/kg gadoxetate. For both exams, we acquired the same unenhanced T1-weighted, T2-weighted, and diffusion-weighted sequences, followed by contrast-enhanced T1-weighted sequences during the dynamic and hepatobiliary phases (HBP) (at 20 min for gadoxetate, at 120 min for gadobenate). Three experienced unaffiliated readers independently evaluated each exam in blinded, randomized order for lesion nature (benign/malignant) and specific lesion diagnosis. McNemar test, Wald tests. paired t-tests and κ statistics were used.

Results
A total of 208 FLLs (108 malignant and 100 benign) were confirmed at final diagnosis. Sensitivity and specificity for malignant/benign differentiation ranged from 91.6% to 99.1% and from 87.5% to 90.5% for gadobenate, and from 86.0% to 91.6% and from 79.7% to 83.6% for gadoxetate. Significantly (p ≤ 0.025) higher values for gadobenate were determined for all diagnostic performance parameters except for sensitivity and negative predictive value for one reader. Significantly (p < 0.001) greater accuracy and confidence for specific lesion diagnosis was achieved with gadobenate for two of three blinded readers. Interreader agreement for malignant/benign differentiation was better with gadobenate (κ = 0.91 versus κ = 0.72).

Conclusion
Gadobenate was superior to gadoxetate for the differentiation and diagnosis of malignant and benign FLLs for two of three readers. Further confirmatory studies that include a wider representation of different types of FLLs are warranted.

Relevance statement
Better diagnostic performance and greater confidence in the characterization of FLLs with gadobenate might improve patient management decisions and timings, and potentially lead to better patient outcomes.

Key Points

Better diagnostic performance for the differentiation of FLLs was achieved with gadobenate for two of three readers.

Reader confidence for lesion diagnosis was greater with gadobenate.

Superior dynamic phase imaging with gadobenate was crucial for accurate lesion diagnosis.

Graphical Abstract
Pulmonary regional blood flow: validation of low-dose two-volume dynamic CT perfusion imaging in a swine model
Authors: Zhao Yixiao , Luu Nile , Hubbard Logan , Malkasian Shant , Molloi Sabee 
Published: February 2025

Abstract

Background
We aimed to validate a low-dose two-volume pulmonary computed tomography (CT) perfusion technique.

Methods
Five Yorkshire swine (weight 53.6 ± 2.6 kg) underwent 21 independent CT perfusion acquisitions. Intravenous contrast material (370 mg/mL iodine, 0.5 mL/kg) and saline chaser (0.5 mL/kg) were injected at 5 mL/s for each acquisition. Two-volume and multivolume dynamic CT perfusion data were acquired using a 320-slice CT, with multivolume measurements serving as the reference standard. The two-volume CT perfusion involved a low-dose (50 mA) volume scan before contrast injection and a diagnostic (300 mA) volume scan after bolus-tracking in the main pulmonary artery at the peak contrast enhancement. Multivolume CT perfusion included 15–20 volume scans for blood flow measurement. Paired sample t-test, linear regression, and Bland–Altman analysis compared both global and regional two-volume perfusion measurements to the reference standard. The reproducibility of the two-volume CT perfusion was assessed from two independent measurements under the same perfusion condition.

Results
Two-volume global perfusion measurements (P
2V) were related to reference multivolume (P
MV) measurements by P
2V = 0.96 × P
MV + 0.45 (r = 0.92), with a root-mean-square error of 1.29 mL/min/g and a root-mean-square deviation of 1.29 mL/min/g. The CT dose index for the two-volume and multivolume CT perfusion measurements were 9.3 mGy and 184.8 mGy, respectively.

Conclusion
We successfully validated a prospective, two-volume CT perfusion technique in a swine model. The findings affirm the feasibility of accurate and reproducible pulmonary blood flow measurement.

Relevance statement
This two-volume CT pulmonary perfusion technique, validated in a swine model, demonstrates the feasibility of blood flow measurement with a substantial reduction in radiation exposure. It could allow low-dose regional blood flow measurement in the assessment of pulmonary artery disease in humans.

Key Points

Lung perfusion can be measured in mL/min/g using a prospective, two-volume CT technique.

Flow measurement is achievable in a swine model with a radiation dose as low as 9.3 mGy.

CT angiography and perfusion can be acquired following a single contrast injection.

Graphical Abstract
Effectiveness and safety of transarterial chemoembolization combined with PD-1 inhibitors and lenvatinib for unresectable intrahepatic cholangiocarcinoma
Authors: Huang Jin-Tao , Hu Di , Hong Xin , Zhou Wen-Jie , Shen Jian , Lv Peng-Hua , Zhu Xiao-Li 
Published: February 2025

Abstract

Background
The objective of this study was to evaluate the therapeutic effectiveness and safety of transarterial chemoembolization (TACE) combined with programmed cell death-1 (PD-1) inhibitors and lenvatinib in the treatment of unresectable intrahepatic cholangiocarcinoma (uICC).

Methods
This multicenter retrospective study screened patients with uICC who underwent TACE in combination with PD-1 inhibitors and lenvatinib between January 2019 and June 2023. Tislelizumab or camrelizumab (200 mg) was intravenously administered every three weeks. The daily dose of lenvatinib was 8 mg for patients weighing < 60 kg and 12 mg for those weighing ≥ 60 kg. In cases of disease progression, the therapeutic strategy was adjusted based on the clinical condition and individual patient’s treatment preferences. Options included transitioning to standard or supportive care or continuing treatment with TACE in combination with PD-1 inhibitors and lenvatinib. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events (AEs).

Results
A total of 59 patients with uICC were included. Over a median follow-up period of 32.3 months, the median OS and PFS were 25.8 months (95% confidence interval [CI]: 17.9–33.7) and 9.5 months (95% CI: 7.9–11.0), respectively. The ORR was 55.9%, and the DCR was 96.6%. Grade 3 or four AEs were observed in 15 of 59 patients (25.4%).

Conclusion
TACE combined with PD-1 inhibitors and lenvatinib demonstrated a promising therapeutic potential with a manageable safety profile for patients with uICC.

Relevance statement
The combination of TACE, PD-1 inhibitors, and lenvatinib represents a novel therapeutic option for patients with uICC.

Key Points

TACE plus PD-1 inhibitors and lenvatinib represent a promising therapeutic strategy for uICC.

The safety profile of TACE plus PD-1 inhibitors and lenvatinib was manageable.

This study demonstrated improved outcomes compared to prior standard-of-care treatments.

Graphical Abstract
Evaluation of usability, feasibility and acceptance of the digital training diary Trainingslog for individuals with axSpA: a mixed-method study
Authors: Pfyl Neva , Ettlin Lea , Niedermann Karin , Rausch Anne-Kathrin 
Published: February 2025

Abstract

Background
Physical activity (PA), including regular exercise, is essential for the successful management of axial spondyloarthritis (axSpA). To promote a physically active lifestyle, a digital training diary (Trainingslog) was developed in an user-centered approach by the Swiss Ankylosing Spondylitis Association (SVMB). A training diary promotes PA through feedback, goal setting and self-monitoring, which can also be used for PA counselling by physiotherapists (PT). Usability, feasibility and acceptance are essential for the successful implementation of a mobile Health Intervention such as the Trainingslog. The study objective is to evaluate the usability, feasibility and acceptance of the Trainingslog for individuals with axSpA and PTs.

Methods
A mixed-methods design was performed among potential end-users of the Trainingslog. Quantitative data was collected by use of questionnaires (System Usability Scale (SUS, 0-100 scale), user version of the Mobile App Rating Scale (uMARS, 5 point scale)) and number of training entries. Subsequently, qualitative data was gathered through semi-structured online focus groups or individual interviews.

Results
11 PTs (9 women, mean age 52.5 [SD 15.6]) and 10 individuals with axSpA (6 women, mean age 48 [SD 13.4]) participated. The quantitative data showed mean SUS scores for usability of 82.5 [SD 21.76] for PTs and 77.0 [SD 9.34] for individuals with axSpA. The mean uMARS sector B scores for feasibility were 4.2 [SD 0.49] for PTs and 4.1 [SD 0.38] for individuals with axSpA. Acceptance, as indicated by the uMARS results (mean score > 3 in Sectors E and F for both groups), was given. But there was a lower-than-expected agreement in the training entries, with 59.86% of entries matching between the Trainingslog and the paper diary. The qualitative analysis unveiled that while usability and feasibility were good, acceptance was lower, primarily due to the use of a web-based link instead of an app version.

Conclusion
The Trainingslog showed a good usability and feasibility, while the acceptance was lower than expected. Acceptance could be increased by offering the Trainingslog as an app-based version, along with implementing additional recommendations for enhancement. Consequently, the Trainingslog has the potential to be applied in PA counselling by PTs or as a self-monitoring tool for individuals with axSpA.
Enhanced adsorption of phenol using EDTA-4Na- and KOH-modified almond shell biochar
Authors: Chen Yanqin , Wang Donghui , Wang Xueli , Wu Jing , Song Shifang 
Published: February 2025

Abstract
To enhance the performance of biochar made from almond shells for adsorption of phenol pollutants in water, we prepared an almond shell-based biochar and modified it through combined pyrolysis with KOH and EDTA-4Na at 750 °C, yielding almond shell-based modified activated carbon (A-BC); the mass ratio of biochar, EDTA-4Na, and KOH was 1:1:3.
A-BC was characterized by using Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, the Brunauer–Emmett–Teller method, and X-ray Diffraction. The adsorption conditions of A-BC for phenol were optimized through single-factor experiments, and the adsorption mechanism was explored through kinetics and thermodynamics assays. The results show that A-BC exhibits a honeycomb-like structure with a specific surface area of 1050 m2 g−1 and a micropore ratio of 86%. A-BC is rich in functional groups (-OH, -CH2, N–C, C-H, N–H) closely related to phenol adsorption. The adsorption of phenol by A-BC is a spontaneous exothermic process involving both physical adsorption and chemical adsorption (including hydrogen bonding and π-π interactions). The pseudo-second-order kinetic model adequately describes the adsorption process, which consists of liquid film diffusion, surface adsorption, and intraparticle diffusion stages. At 25 °C, with an A-BC dosage of 1.0 g L−1, initial phenol concentration of 400 mg L−1, and contact time of 60 min, A-BC exhibited significant adsorption capacities of 161 and 149 mg g−1 for simulated water and phenol-containing wastewater from coal chemical industries, respectively. A-BC demonstrated good reuse performance and strong adsorption capacity for phenol, indicating its potential application in treating phenol-containing wastewater from coal chemical industries.