bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between remnant cholesterol and bone mineral density in US adults: the National Health and Nutrition Examination Survey (NHANES) 2013–2018
Authors: Xiao Peilun , Wang Zhihang , Lu Zeyao , Liu Shijia , Huang Chongjun , Xu Ying , Tian Ye 
Published: May 2024

Abstract
Background
Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans.

Methods
This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013–2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD.

Results
This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (β= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P < 0.001). Moreover, RC had a stronger effect on total spine BMD than total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).

Conclusions
This study found that serum RC was negatively related to total spine BMD in U.S. adults. These findings emphasized the important role of RC in bone health in American adults.
A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients
Authors: Xiong Si-Ping , Wang Chun-Hua , Zhang Mei-fang , Yang Xia , Yun Jing-Ping , Liu Li-Li 
Published: May 2024

Abstract
Background
Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC.

Methods
A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell’s concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis.

Results
A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time.

Conclusions
The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.
Scurvy masquerading as IgA vasculitis
Authors: Kassa Hanna L. , Singh S. , Douglas-Jones M. , Schermbrucker Gill , De Lange J , Phoya Frank , Butters Claire , Hlela Carol , Coetzee Ashton , Banderker Ebrahim , Webb Kate 
Published: May 2024

Abstract
Background
Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children.

Case presentation
We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy.

Conclusion
Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential.
Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.
Role of surgical simulation on self-reported confidence level on cardiothoracic surgical trainees
Authors: Yean Len En , Hashim Shahrul Amry bin 
Published: May 2024

Abstract
Background
Simulated self-practice using simulation models could improve fine motor skills and self confidence in surgical trainees.

Aims
The purpose of this study is to evaluate on self-reported confidence level in cardiothoracic surgical trainees by using surgical simulation models.

Methods
We conducted a cross-sectional study on all surgeons (n=10) involved in MIS simulation training. All surgeons are required to perform on three minimally invasive surgery (MIS) procedures (Mitral Valve Repair, Mitral Valve Replacement and Aortic Valve Replacement). A questionnaire was designed based on two existing scales related to self-confidence, the surgical self-efficacy scale [SSES] and the perceived competency scale [PCS]. We assessed their self-confidence (before and after training) in the use of simulation in MIS procedures using rating scales 1-5. The mean score was calculated for each domain and used as the predictor variable. We also developed six questions (PCS) using Objective Structured Assessment of Technical Skills (OSAT) related to each domain and asked participants how confident they were after performing each MICS procedure.

Results
The mean score was 4.7 for all assessed domains, except "knowledge" (3.8). Surgeons who had performed one or more MIS procedures had higher scores (P<0.05). There was no correlation between the number of MIS procedures performed and self-confidence scores.

Conclusions
The results indicate that the cardiac surgery training based on MIS simulation improves trainees and consultants in terms of the level of self-confidence. Although surgeons generally have high levels of self-confidence after simulation training in MIS cardiac procedures, there is still room for improvement with respect to technical skills related to the procedure itself and its results.
Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages
Authors: Nomaki Kohei , Fujikawa Risako , Masuda Takahiro , Tsuda Makoto 
Published: May 2024

AbstractCD11c-positive (CD11c+) microglia have attracted considerable attention because of their potential implications in central nervous system (CNS) development, homeostasis, and disease. However, the spatiotemporal dynamics of the proportion of CD11c+ microglia in individual CNS regions are poorly understood. Here, we investigated the proportion of CD11c+ microglia in six CNS regions (forebrain, olfactory bulb, diencephalon/midbrain, cerebellum, pons/medulla, and spinal cord) from the developmental to adult stages by flow cytometry and immunohistochemical analyses using a CD11c reporter transgenic mouse line, Itgax-Venus. We found that the proportion of CD11c+ microglia in total microglia varied between CNS regions during postnatal development. Specifically, the proportion was high in the olfactory bulb and cerebellum at postnatal day P(4) and P7, respectively, and approximately half of the total microglia were CD11c+. The proportion declined sharply in all regions to P14, and the low percentage persisted over P56. In the spinal cord, the proportion of CD11c+ microglia was also high at P4 and declined to P14, but increased again at P21 and thereafter. Interestingly, the distribution pattern of CD11c+ microglia in the spinal cord markedly changed from gray matter at P4 to white matter at P21. Collectively, our findings reveal the differences in the spatiotemporal dynamics of the proportion of CD11c+ microglia among CNS regions from early development to adult stages in normal mice. These findings improve our understanding of the nature of microglial heterogeneity and its dynamics in the CNS.
Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction
Authors: Chen Hui , Nie Ping , Li Jingling , Wu Yongqi , Yao Bo , Yang Yabing , Lash Gendie E. , Li Ping 
Published: May 2024

AbstractAbnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.
SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure
Authors: Pannu Sonal , Exline Matthew C. , Bednash Joseph S. , Englert Joshua A. , Diaz Philip , Bartlett Amy , Brock Guy , Wu Qing , Davis Ian C. , Crouser Elliott D. 
Published: May 2024

Abstract
Background
The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.

Methods
We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named “SCARLET” (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.

Discussion
Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.

Trial registration
The trial was registered at www.clinicaltrials.gov on 5/31/2023 (NCT05881135).

Trial status
Currently enrolling.
Suppressing random noise in seismic signals using wavelet thresholding based on improved chaotic fruit fly optimization
Authors: Yang Feng , Liu Jun , Hou Qingming , Wu Lu 
Published: May 2024

AbstractSuppressing random noise in seismic signals is an important issue in research on processing seismic data. Such data are difficult to interpret because seismic signals usually contain a large amount of random noise. While denoising can be used to reduce noise, most denoising methods require the prior estimation of the threshold of the signals to handle random noise, which makes it difficult to ensure optimal results. In this paper, we propose a wavelet threshold-based method of denoising that uses the improved chaotic fruit fly optimization algorithm. Our method of selects uses generalized cross-validation as the objective function for threshold selection. This objective function is optimized by introducing an adjustment coefficient to the chaotic fruit fly optimization algorithm, and the optimal wavelet threshold can then be obtained without any prior information. We conducted denoising tests by using synthetic seismic records and empirical seismic data acquired from the field. We added three types of noise, with different average signal-to-noise ratios, to synthetic seismograms containing noise with original intensities of − 5, − 1, and 4 dB, respectively. The results showed that after denoising, the signal-to-noise ratios of the three types of noise increased to 7.12, 10.04, and 14.26, while the mean-squared errors in the results of the proposed algorithm decreased to 0.006, 0.0031, and 0.0012, respectively.
A longer time to relapse is associated with a larger increase in differences between paired primary and recurrent IDH wild-type glioblastomas at both the transcriptomic and genomic levels
Authors: Ho Wei-Min , Chen Chia-Ying , Chiang Tai-Wei , Chuang Trees-Juen 
Published: May 2024

AbstractGlioblastoma (GBM) is the most common malignant brain tumor in adults, which remains incurable and often recurs rapidly after initial therapy. While large efforts have been dedicated to uncover genomic/transcriptomic alternations associated with the recurrence of GBMs, the evolutionary trajectories of matched pairs of primary and recurrent (P-R) GBMs remain largely elusive. It remains challenging to identify genes associated with time to relapse (TTR) and construct a stable and effective prognostic model for predicting TTR of primary GBM patients. By integrating RNA-sequencing and genomic data from multiple datasets of patient-matched longitudinal GBMs of isocitrate dehydrogenase wild-type (IDH-wt), here we examined the associations of TTR with heterogeneities between paired P-R GBMs in gene expression profiles, tumor mutation burden (TMB), and microenvironment. Our results revealed a positive correlation between TTR and transcriptomic/genomic differences between paired P-R GBMs, higher percentages of non-mesenchymal-to-mesenchymal transition and mesenchymal subtype for patients with a short TTR than for those with a long TTR, a high correlation between paired P-R GBMs in gene expression profiles and TMB, and a negative correlation between the fitting level of such a paired P-R GBM correlation and TTR. According to these observations, we identified 55 TTR-associated genes and thereby constructed a seven-gene (ZSCAN10, SIGLEC14, GHRHR, TBX15, TAS2R1, CDKL1, and CD101) prognostic model for predicting TTR of primary IDH-wt GBM patients using univariate/multivariate Cox regression analyses. The risk scores estimated by the model were significantly negatively correlated with TTR in the training set and two independent testing sets. The model also segregated IDH-wt GBM patients into two groups with significantly divergent progression-free survival outcomes and showed promising performance for predicting 1-, 2-, and 3-year progression-free survival rates in all training and testing sets. Our findings provide new insights into the molecular understanding of GBM progression at recurrence and potential targets for therapeutic treatments.
Interactive Malaysian Childhood Healthy Lifestyle (i-MaCHeL) programme: a single-arm pilot study
Authors: Rashid Ahmad Faezi Ab , Syed Saadun Tarek Wafa Sharifah Wajihah Wafa , Talib Ruzita Abd , Bakar Nor Mazlina Abu 
Published: May 2024

Abstract
Background
The growing obesity epidemic in Malaysia presents a public health challenge that requires innovative intervention strategies. In an effort to address this problem, an Interactive Malaysian Childhood Healthy Lifestyle (i-MaCHeL) programme, which is a web-based initiative designed for preschool child–parent dyads offers a novel approach. Nevertheless, the success of such a web-based intervention depends on several interrelated factors. This research aims to examine the feasibility of i-MaCHeL in the Malaysian context, its usability for preschool child–parent dyads, and the acceptability of the programme among these user groups.

Methods
This was a single-arm pilot study involving 46 child–parent dyads recruited from six government preschools in Terengganu, Malaysia. The preschools were selected using a cluster random sampling technique at the preschool level. The intervention feasibility was determined based on the retention rate of participants in the pilot study. The System Usability Scale (SUS) and intervention process evaluation were used to assess the usability and acceptability of the web-based i-MaCHeL programme.

Results
The retention data demonstrated that 42 out of 46 participants completed the 13-week intervention programme, which showed that the overall retention rate was 91.3%. A mean (SD) SUS score of 84.70 (13.82) was obtained from parents, indicating that the web-based i-MaCHeL had an acceptable usability level. The mean scores of the process evaluation items ranged from 4.52 (0.63) to 4.83 (0.38), demonstrating that the web-based i-MaCHeL was highly accepted by the parents. The acceptability data also indicated that at least 92.9% (39/42) of the parents agreed/strongly agreed that the web content, programme duration, intervention dose, WhatsApp group, and delivery mode were appropriate.

Conclusions
According to these findings, the i-MaCHeL intervention using a web-based approach was feasible, usable, and acceptable as part of a weight-related behaviour change intervention for preschool child–parent dyads. This pilot study demonstrated that the web-based i-MaCHeL was feasible and promising for delivering weight-related behavioural intervention to child–parent dyads.

Trial registration
ClinicalTrials.gov, NCT04711525. Registered on January 15, 2021.