bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung ultrasound outperforms symptom-based screening to detect interstitial lung disease associated with rheumatoid arthritis
Authors: Vermant Marie , Kalkanis Alexandros , Jacob Joseph , Goos Tinne , Cortesi Emanuela Elsa , Cypers Heleen , De Crem Nico , Follet Tine , Gogaert Stefan , Neerinckx Barbara , Taelman Veerle , Veyt Nathalie , De Sadeleer Laurens J , Verschueren Patrick , Wuyts Wim 
Published: February 2025

ObjectivesInterstitial lung disease associated with rheumatoid arthritis (RA-ILD) is linked to high mortality. Currently, effective screening tools are lacking. We assessed the role of symptoms and lung ultrasound (LUS) as potential screening tools.Methods116 adult patients with RA presenting to the rheumatology outpatient clinic underwent high-resolution CT (HRCT) scans, pulmonary function tests, LUS (72 zones) and completed a Visual Analogue Scale (VAS) for cough and modified Medical Research Council dyspnoea scale (mMRC). Kruskal-Wallis (KW) tests evaluated the correlation between clinical–radiological HRCT score (no ILD, non-specific abnormalities, subclinical ILD or ILD) and the B-lines on LUS, diffusion capacity (DLCO%pred), forced vital capacity (FVC%pred), VAS Cough and mMRC. Sensitivity and specificity analyses were performed to assess symptom-based questionnaires and the number of B-lines to detect RA-ILD. Area under the receiver operating characteristics (AUROC) for detecting clinical ILD and subclinical ILD were calculated.ResultsIn 11.8% of patients, an ILD was detected on HRCT. Additionally, in 5%, a diagnosis of subclinical interstitial lung changes was made. The number of B-lines was most strongly associated with the clinical–radiological score (KW χ²=41.2, p=<0.001). DLCO%pred was also significantly correlated with the clinical–radiological score (KW χ²=27.4, p=<0.001), but FVC%pred, mMRC and VAS cough were not. Cough and dyspnoea only weakly predicted the ILD score in the sensitivity–specificity analyses, while B-lines showed AUROCs>0.9 for predicting subclinical and clinical ILD.ConclusionLUS is a promising tool for early detection of RA-ILD, outperforming symptom-based questionnaires or the presence of dyspnoea or cough.
Explainable models for predicting long-term outcomes in patients with spontaneous intracerebral haemorrhage: a retrospective cohort study
Authors: Yang Kai-Cheng , Jin Yu-Jia , Tang Li-Li , Gao Feng , Tong Lusha 
Published: February 2025

Background and aimRecently, long-term outcomes in patients with spontaneous intracerebral haemorrhage (sICH) have gained increasing attention besides acute-phase characteristics. Predictive models for long-term outcomes are valuable for risk stratification and treatment strategies. This study aimed to develop and validate an explainable model for predicting long-term recurrence and all-cause death in patients with ICH, using clinical and imaging markers of cerebral small vascular diseases from MRI.MethodWe retrospectively analysed data from a prospectively collected large-scale cohort of patients with acute ICH admitted to the Neurology Department of The Second Affiliated Hospital of Zhejiang University between November 2016 and April 2023. After comprehensive variable selection using least absolute shrinkage and selection operator and stepwise Cox regression, we constructed Cox proportional hazards models to predict recurrence and all-cause death. Model performance was evaluated using the concordance index, integrated Brier score and time-dependent area under the curve. Global and local interpretability were assessed using variable importance calculated as SurvSHAP(t) and SurvLIME methods for the entire training set and individual patients, respectively.ResultsA total of 842 eligible patients were included. Over a median follow-up of 36 months (IQR: 12–51), 86 patients (9.1%) died, and 62 patients (6.6%) experienced recurrence of ICH. The concordance indexes for the all-cause death and recurrence models were 0.841 (95% CI 0.767 to 0.913) and 0.759 (95% CI 0.651 to 0.867), respectively, with integrated Brier scores of 0.079 and 0.063. The interpretability maps highlighted age, aetiology of ICH and low haemoglobin as key predictors of long-term death, while cortical superficial siderosis and previous haemorrhage were crucial for predicting recurrence.ConclusionsThis model demonstrates high predictive accuracy and emphasises the crucial factors in predicting long-term outcomes of patients with sICH.
Cortical Morphology Alterations Mediate the Relationship Between Glymphatic System Function and the Severity of Asthenopia
Authors: Chen Yilei , Xu Jun , Kong Yingnan , Kang Yingjie , Gong Zhigang , Wang Hui , Huang Yanwen , Zhan Songhua , Yu Ying , Lv Xiaoli , Tan Wenli 
Published: February 2025

Objectives: This study is aimed at assessing glymphatic function by diffusion tensor image analysis along the perivascular space (DTI‐ALPS) and its associations with cortical morphological changes and severity of accommodative asthenopia (AA).Methods: We prospectively enrolled 50 patients with AA and 47 healthy controls (HCs). All participants underwent diffusion tensor imaging (DTI) and T1‐weighted imaging and completed the asthenopia survey scale (ASS). Differences in brain morphometry and the analysis along the perivascular space (ALPS) index between the two groups were compared. The correlation and mediation analyses were conducted to explore the relationships between them.Results: Compared to HCs, patients with AA exhibited significantly increased sulcal depth in the left superior occipital gyrus (SOG.L) and increased cortical thickness in the left superior temporal gyrus (STG.L), left middle occipital gyrus (MOG.L), left postcentral gyrus (PoCG.L), and left precuneus (PCUN.L). Additionally, patients with AA had a significantly lower ALPS index than HCs. The sulcal depth of the SOG.L was significantly positively correlated with the ASS score in patients with AA, and a positive correlation was found between the cortical thickness of the MOG.L and ASS score. The ALPS index was negatively associated with the sulcal depth of the SOG.L and cortical thickness of the MOG.L. Mediation analysis revealed that the sulcal depth of SOG.L and cortical thickness of MOG.L partially mediated the impact of the DTI‐ALPS index on the ASS score.Conclusion: Our findings suggested that patients with AA exhibit impaired glymphatic function, which may contribute to the severity of asthenopia through its influence on cortical morphological changes. The ALPS index is anticipated to become a potential imaging biomarker for patients with AA.Trial Registration: Chinese Registry of Clinical Trials: ChiCTR1900028306
Evaluation of Two Multiplexed qPCR Assays for Malaria Detection and Speciation: A Comparative Study With Nested PCR and Microscopy
Authors: Muyidi Ahmed A. , Ayashi Musa A. , Wakid Majed H. , Alghanmi Maimonah S. , Baakdah Fadi M. , Gattan Hattan S. , Alsaady Isra M. , Alsulami Muslimah N. , Albohiri Haleema H. , Altwaim Sarah A. , Eisa Zaki M. , Brek Thamer M. 
Published: February 2025

Background: Malaria is a deadly vector‐borne parasitic disease spread by the bite of an infective female Anopheles mosquito. In routine malaria diagnosis, microscopic examination is generally regarded as the gold standard. Our study sought to evaluate the diagnostic precision of two commercially accessible quantitative PCR (qPCR) kits, in contrast to light microscopy and nested multiplex PCR (NM‐PCR).Methods: This cross‐sectional study in southwest Saudi Arabia included 92 febrile patients meeting the inclusion criteria. Detection of Plasmodium species used light microscopy, NM‐PCR, and qPCR kits (RealStar and Viasure). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curves were calculated. Statistical analysis was performed using SPSS v25, with significance set at p ≤ 0.05.Results: Light microscopy detected 92.4% of cases, NM‐PCR detected 73.9%, and RealStar and Viasure detected 92.4% and 95.7%, respectively. Viasure showed the highest sensitivity (97.6%) and NPV (50%), while NM‐PCR had superior specificity (71.4%). For species identification, Plasmodium falciparum detection was highest with RealStar (85%). Mixed infections were better identified by Viasure (34.6%). RealStar excelled in Plasmodium vivax detection (area under the curve [AUC] = 90%). qPCR detected low parasitemia levels missed by microscopy.Conclusions: The qPCR kits, particularly Viasure, demonstrated superior sensitivity for detecting Plasmodium species and identifying mixed infections compared to light microscopy and NM‐PCR. While light microscopy showed higher specificity and PPV, qPCR effectively detected low parasitemia levels missed by microscopy, highlighting its value in improving malaria diagnostics.
Effect of Vestibular‐Oriented Balance Training on Postural Control and Risk of Fall in Patients With Parkinson’s Disease
Authors: Khallaf Mohamed , Jaber Hatem , Alameri Mansoor , Magdy Dina , Kamal Hend , Hassanin Mohamed , Mousa Mohamed , Fayed Eman 
Published: February 2025

Background: Parkinson’s disease is a neurodegenerative disorder that affects balance and increases the risk of falling by compromising vestibular signal processing.Objectives: This study aims to assess the impact of vestibular‐oriented balance training on postural control and fall risk among people in the middle stages of PD.Methods: Forty middle‐stage individuals with PD were assigned to the vestibular‐oriented balance training (study group) or the traditional balance training (control group). Outcome measures including Functional Gait Assessment (FGA) and modified Clinical Test of Sensory Interaction on Balance (mCTSIB) using the Biodex Balance System were measured before, immediately after and 4 weeks after treatment.Results: There was a significant group interaction by time for all outcome measures (p < 0.001). The results showed that the difference in the FGA and mCTSIB scores from baseline was significant between the two groups at all time points (p < 0.001). The study group showed significant sustained improvements in the FGA score overtime, while the control group had a significant improvement at Week 8 but that did not last to Week 12. In mCTSIB, the study group improved significantly in all test conditions (p < 0.001), while the control group showed significant improvement only in Conditions 1 and 2, without lasting effects at Week 12 (p > 0.05).Conclusions: The findings indicate that the implementation of vestibular‐oriented balance training during the middle stage of PD might have a notable and lasting impact on both postural control and the risk of falls.
Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatin in patients with HER2-negative BC and HRD –long-term survival of the GeparOLA study
Authors: Fasching Peter A. , Schmatloch Sabine , Hauke Jan , Rey Julia , Jackisch Christian , Klare Peter , Link Theresa , Hanusch Claus , Huober Jens , Stefek Andrea , Holtschmidt Johannes , Schneeweiss Andreas , Uleer Christoph , Schmitt Wolfgang D. , Doering Gabriele , Rhiem Kerstin , Denkert Carsten , Schmutzler Rita K. , Solbach Christine , Hahnen Eric , Hartkopf Andreas , Untch Michael , Bjelic-Radisic Vesna , Nekljudova Valentina , Blohmer Jens-Uwe , Loibl Sibylle 
Published: February 2025

Abstract
Backgound: The GeparOLA study evaluated paclitaxel(P) plus olaparib(O) in neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer (eBC) with homologous recombination deficiency (HRD). HRD was defined by high HRD-score or germline(g)/tumor(t) BRCA1/2 mutations (g/tBRCA1/2mut). Here, we report long-term outcome data. Patients and Methods: GeparOLA (NCT02789332) was a randomized, multicenter, prospective, open-label, phase II trial. Patients with HER2-negative eBC, HRD, indication for chemotherapy (cT2-cT4a-d or cT1c and cN+ or cT1c and pNSLN+ or cT1c and triple-negative[TN]BC or cT1c and Ki-67&gt;20%), were randomly assigned to P+O or P+carboplatin(Cb), both followed by epirubicin+cyclophosphamide(EC). Long-term efficacy endpoints were secondary endpoints and included invasive disease-free survival(iDFS), distant disease-free survival(DDFS) and overall survival(OS). Results: Between 09/2016 and 07/2018, 107 patients were randomized and 106 (PO N=69;PCb N=37) started treatment. The median age was 47.0 years; 35.8% had cT1 tumors; 31.4% were cN+; 86.8% had G3 tumors; 89.6% had Ki-67&gt;20% and 72.6% were TN. After median follow-up of 49.8 months, 18(15 PO; 3 PCb) iDFS events and 7(6 PO; 1 PCb) deaths were reported. The 4-year iDFS (76.0%PO vs 88.5%PCb, HR=2.86 [95%CI 0.83-9.90],log-rank p=0.081), DDFS (81.2%PO vs 93.4%PCb, HR=3.03 [95%CI 0.67-13.67],log-rank p=0.129) and OS (89.2%PO vs 96.9%PCb, HR=3.27 [95%CI 0.39-27.20],log-rank p=0.244) tended to be inferior with O. Patients without g/tBRCA1/2mut benefited from Cb [7/30 patients had iDFS/DDFS events in PO vs 0/16 in PCb]. Conclusion: For HER2-negative eBC with HRD, olaparib showed a tendency for inferior outcomes compared to carboplatin, particularly in patients without g/tBRCA1/2mut. In patients with g/tBRCA1/2mut olaparib may replace carboplatin.
ASH2L Deficiency in Smooth Muscle Drives Pulmonary Vascular Remodeling
Authors: Zhang Jing , Gu Xia , Cheng Tian-Le , Qi Yong-Jia , Liu Dao-Yan , Wu Na , Wang Da-Peng , Huang Yu , Zhu Zhi-Ming , Fan Ye 
Published: February 2025

BACKGROUND:
Histone H3 lysine 4 methylation is one of the most abundant epigenetic modifications, which has been recently linked to vascular remodeling in pulmonary hypertension (PH). SET1/MLL methyltransferase complexes comprise the main enzymes responsible for methylating H3 lysine 4, yet their roles in vascular remodeling and PH are not fully understood. We aim to assess the contribution of ASH2L, a core SET1/MLL family member, to the pathogenesis of PH.

METHODS:
Human pulmonary artery specimens and primary vascular cells, smooth muscle cell (SMC)-specific ASH2L-deficient mice, rats with SMC-specific ASH2L overexpression, mass spectrometry, immunoprecipitation, and chromatin immunoprecipitation were used to define the role of ASH2L in PH.

RESULTS:
Analysis of bulk RNA-sequencing data sets from human lung vessels identified ASH2L as the only differentially expressed SET1/MLL family member in PH compared with healthy controls. Decreased ASH2L expression in human pulmonary arteries correlated with the clinical severity of PH, which contrasted with elevated H3 lysine 4 methylation and was primarily localized to SMCs. Depletion of ASH2L promoted whereas its restoration ameliorated SMC proliferation and vascular remodeling in PH. Mechanistically, we revealed that ASH2L functioned independently of the canonical H3 lysine 4 trimethylation-based transcriptional activation, while it formed a protein complex with KLF5 and FBXW7, thereby accelerating the ubiquitin-proteasomal degradation of KLF5. NOTCH3 was discovered as a new downstream target of KLF5, and the loss of ASH2L promoted the recruitment of KLF5 to the NOTCH3 promoter, thus enhancing NOTCH3 expression. Pharmacological blockage of KLF5 attenuated PH in chronic hypoxia-exposed SMC-specific ASH2L-deficient mice and sugen/hypoxia-challenged rats.

CONCLUSIONS:
This study demonstrated that ASH2L deficiency causatively affects SMC proliferation and lung vascular remodeling that is partially mediated through KLF5-dependent NOTCH3 transcription. Activating ASH2L or targeting KLF5 might represent potential therapeutic strategies for PH.
Endothelial PPARδ Ablation Exacerbates Vascular Hyperpermeability via STAT1/CXCL10 Signaling in Acute Lung Injury
Authors: Hong Huiling , Wu Yalan , Li Yangxian , Han Yumeng , Cao Xiaoyun , Wu Vivian Wei Yan , Chan Thomas Ting Hei , Zhou Jingying , Cao Qin , Lui Kathy O. , Wong Chun-Kwok , Dai Zhiyu , Tian Xiao Yu 
Published: February 2025

BACKGROUND:
Vascular hyperpermeability is one of the hallmarks of acute lung injury, contributing to excessive inflammation and respiratory failure. The PPARδ (peroxisome proliferator-activated receptor delta) is an anti-inflammatory transcription factor, although its role in endothelial barrier function remains unclear. Here, we studied the essential role of PPARδ in maintaining vascular endothelial barrier integrity during lung inflammation and investigated the underlying mechanisms.

METHODS:

Endothelial cell (EC)–selective PPARδ knockout mice (Ppard
EC-KO
) and littermate control mice (Ppard
EC-WT
) received lipopolysaccharide injection to induce acute lung injury. Lung inflammation, pulmonary vascular leakage, and mouse mortality were monitored. Single-cell RNA sequencing was performed on sorted mouse lung ECs.

RESULTS:

Ppard
EC-KO
mice exhibited aggravated lung inflammation, characterized by increased leukocyte infiltration, elevated production of proinflammatory cytokines, and higher mortality rates. The enhanced inflammatory responses were associated with increased protein leakage, interstitial edema, and impaired endothelial barrier structure, leading to vascular hyperpermeability in Ppard
EC-KO
mice. Mechanistically, with single-cell RNA sequencing, we identified the emergence of an interferon-activated capillary EC population marked by CXCL10 (C-X-C motif chemokine 10) expression following lipopolysaccharide challenge. PPARδ silencing significantly increased CXCL10 expression in ECs through activating STAT1. Notably, CXCL10 treatment induced degradation of tight junction proteins ZO-1 (zonula occluden-1) and claudin-5 through the ubiquitin-proteasome system, disrupting membrane junction continuity in ECs. Administration of anti-CXCL10 antibody or CXCL10 receptor antagonist AMG487 suppressed both lipopolysaccharide-induced lung inflammation and vascular leakage in Ppard
EC-KO
mice.

CONCLUSIONS:
These results highlighted a novel anti-inflammatory role of PPARδ in ECs by suppressing CXCL10-mediating vascular hyperpermeability. Targeting the CXCL10 signaling shows therapeutic potential against vascular injury in acute lung injury.
Competition and Isomorphism
Authors: Sun Yanfei 
Published: February 2025

Abstract
This article studies organizational isomorphism as a force of religious change and highlights the importance of competition in inciting the isomorphic behaviors of religious organizations. Empirically, it tackles the puzzle of why, facing competitive pressure, Chinese Buddhist organizations actively copied organizational traits of their rivals during the Republican China era (1912–1949) and in Taiwan under Chiang Kai-shek (1949–1975), but not in post-Mao mainland China since 1978. Theoretically, it aims to amend the institutional isomorphism theory of DiMaggio and Powell by suggesting that competition remains a significant force in organizational change in the modern age. The analysis suggests that for incumbent religious organizations to launch competitive isomorphic moves, they must meet at least two prerequisites: first, they must acutely perceive competitive pressure; second, without the resources or means to neutralize the challenge, they must learn from their rivals’ strengths to (re)gain dominance. This article also stresses the vital and pervasive role of the state, in terms of its nature and patterned behaviors, in conditioning incumbent organizations’ perceptions of and responses to their rivals.
Global burden of malaria and neglected tropical diseases in children and adolescents, 1990–2019: a population-based, cross-sectional study
Authors: Zheng Jinxin , Zhang Daoqi , Zhang Shunxian , Chen Muxin , Guo Zhaoyu , Guan Shiyang , Liu Yushu , Bergquist Robert , Li Shizhu , Zhou Xiaonong , Feng Xinyu 
Published: February 2025

Objectives To estimate the global burden of malaria and neglected tropical diseases (NTDs) in children and adolescents aged 0–19 years and to analyse trends to inform public health and policy decisions. Design Population-based, cross-sectional study. Setting Global analysis across 204 countries and territories. Participants Children and adolescents aged 0–19 years with malaria and NTDs, stratified by age, gender and location from 1990 to 2019. Main outcome measures Yearly incidence, prevalence, and disability-adjusted life years (DALYs) for malaria and NTDs, age-standardised incidence rates (ASIRs) and age-standardised DALY rates (ASDRs). Results The global burden of malaria and NTDs among children and adolescents aged 0–19 years remains substantial. In 2019, 195.6 million cases of malaria and NTDs were recorded globally, resulting in 43.9 million (95% Uncertainty Interval (UI): 25.0–70.4 million) DALYs. The incidence rate increased until 2005 and then declined. Sub-Saharan Africa had the highest ASDR, while high-income regions had the lowest. Significant ASDR reductions occurred in Andean Latin America and South Asia. The burden was highest in low-Socio-Demographic Index (SDI) regions, with malaria accounting for over 93% of DALYs among children under five. Females had slightly higher incidence rates, while DALYs were evenly distributed between genders. There was an inverse association observed between SDI and ASDRs. Conclusions Malaria and NTDs continue to disproportionately affect children and adolescents in low-SDI regions, especially sub-Saharan Africa. Sustaining gains while accelerating control efforts is the key to successful control progress and ambiguous elimination goals for both malaria and NTDs.
Healthcare professionals’ perspectives of providing end-of-life care for infants, children and young people in acute settings: A multi-site qualitative study
Authors: McLorie Emma Victoria , Hackett Julia , Barrett Laura , Peat George , Weatherly Helen , Hinde Sebastian , Walker Gabriella , Noyes Jane , Oddie Sam , Vasudevan Chakrapani , Feltbower Richard G. , Phillips Bob , Hewitt Catherine , Hain Richard , Subramanian Gayathri , Haynes Andrew , Papworth Andrew , Fraser Lorna Katharine , Murtagh Fliss E.M. 
Published: February 2025

Background: Paediatric end-of-life care is an important part of palliative care, and provides care and support for children in the last days, weeks, months or year of life. However, there is currently a picture of inconsistent and disjointed provision. Despite differences in delivery models across countries and cultures, healthcare professionals need to be able to support families through this difficult time. However, there is limited evidence to base high quality end-of-life care. Aim: To explore healthcare professionals’ experiences of delivering end-of-life care to infants, children and young people, their needs and the factors affecting access and implementation. Design: Qualitative study employing online focus groups, analysed using framework analysis. Setting/participants: Healthcare professionals who provided end-of-life care to infants, children and young people, across cancer centres and neonatal and paediatric intensive care units. Results: A total of 168 professionals from 13 tertiary hospitals participated in 23 focus groups. Three themes highlighted many barriers to delivering optimal care: (1) Professional perceptions of end-of-life care; (2) What we want to provide versus what we can and (3) Workforce and sustainability: Healthcare professional support. These illustrate professionals’ awareness and desire to deliver high-quality care, yet are constrained by a number of factors, suggesting the current system is not suitable. Conclusions: This study provides an in-depth exploration of paediatric end-of-life care, from those professionals working across the settings accounting for the majority of end-of-life care delivery. Many of these issues could be resolved by investment in: funding, time, education and support to enable delivery of increasingly complex end-of-life care.