bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dosimetric comparison of non-coplanar volumetric modulated arc therapy and non-coplanar fixed field intensity modulated radiation therapy in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for brain metastases
Authors: Zeng Huaqu , Zhong MinZhi , Chen Zongyou , Tang Shukui , Wen Zunbei 
Published: January 2025

ObjectiveThe aim of this study was to investigate the dosimetric differences between non-coplanar volumetric modulated arc therapy (VMAT) and non-coplanar fixed-field intensity-modulated radiotherapy (IMRT) in hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for brain metastases using the Monaco treatment planning system (TPS).MethodA total of 22 patients with brain metastases were retrospectively enrolled. Two radiotherapy treatment plans were designed for each patient: non-coplanar VMAT and non-coplanar fixed field IMRT. The dose distribution of targets and organs at risk (OAR), the number of monitor units (MUs), and pre-treatment plan verification were compared between the two plans while meeting the prescribed dose requirements of the target volume.ResultsThere were no significant differences in V50, V55, Dmax, heterogeneity index (HI) and conformity index (CI) of target PGTV between the two plans (p&gt;0.05). For PTV-brain-SIB, there was no significant difference in D98% between IMRT and VMAT (p=0.103). VMAT significantly improved the V30 of PTV-brain-SIB (p&lt;0.001), decreased HI (p=0.003), and increased CI (p&lt;0.001). There were no significant differences in the Dmax to the brain stem, left and right lens, optic chiasm, pituitary gland, and left and right hippocampus between the two plans (p&gt;0.05). Compared with IMRT, VMAT significantly reduced the Dmax to the left and right eyes (p&lt;0.001) and significantly increased the Dmax to the right inner ear (p=0.010). There was no significant difference in the Dmax to the left inner ear between VMAT and IMRT (p=0.458). Compared with IMRT, VMAT significantly reduced the Dmax to the left optic nerve (p=0.006), but significantly increased the Dmax to the right optic nerve (p=0.001). There was no significant difference in the Dmax to the left and right hippocampus between VMAT and IMRT (p&gt;0.05), but VMAT significantly increased the D100% (p&lt;0.05) compared with IMRT. Compared with VMAT, IMRT significantly reduced the MU (p&lt;0.001) but VMAT has a higher treatment efficiency than IMRT, with an average reduction of 41 seconds (294.1 ± 16.4 s for VMAT, 335.8 ± 34.9 s for IMRT, p&lt;0.001). Under the conditions of 3%/2 mm, and 2%/2 mm, the gamma passing rate of the IMRT QA was improved compared to VMAT, with an average increase of 0.6%, p=0.013, and 1.7%, p&lt;0.001, respectively.ConclusionBoth non-coplanar VMAT and non-coplanar fixed field IMRT based on the Monaco TPS produce clinically acceptable results for HA-WBRT+SIB in patients with brain metastases. Compared with IMRT, VMAT has better dose distribution in the target volume and treatment efficiency, but IMRT can better protect the hippocampus and reduce the number of MUs.
Development and approval of a Lasso score based on nutritional and inflammatory parameters to predict prognosis in patients with glioma
Authors: Li Huixian , Hong Hui , Zhang Jinling 
Published: January 2025

ObjectivesPreoperative peripheral hematological indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and prognostic nutritional index (PNI), exhibit promise as prognostic markers for glioma. This study evaluated the prognostic value of a combined scoring system incorporating NLR, PLR, MLR, and PNI, and developed a nomogram to predict glioma prognosis.MethodsData on preoperative NLR, PLR, MLR, and PNI were collected from 380 patients with pathologically diagnosed glioma (266 in the training cohort, 114 in the validation cohort). The Least Absolute Shrinkage and Selection Operator (Lasso) was employed to select relevant hematological indicators and generate a Lasso score. A nomogram was constructed utilizing Cox regression and Lasso variable selection. This nomogram incorporated the Lasso score, age, pathological type, chemotherapy status, and Ki67 expression to predict overall survival (OS). Model performance was evaluated utilizing Harrell’s c-index, calibration curves, DCA, and clinical utility (stratification into low-risk and high-risk groups), and verified utilizing the independent validation cohort.ResultsA total of 380 glioma patients were enrolled and separated into training (n = 266) and validation (n = 114) cohorts. The two cohorts demonstrated no significant differences in baseline characteristics. NLR, PLR, MLR, and PNI from the training dataset were utilized for Lasso calculation. Multivariable analysis indicated that age, pathological grade, chemotherapy status, Ki-67 expression, and the Lasso score were independent predictors of OS and were then included in the nomogram. The nomogram model based on the training cohort had a C index of 0.742 (95% CI: 0.700-0.783) and AUC values of 0.802, 0.775, and 0.815 for ROC curves at 1, 3, and 5 years after surgery. The validation cohort derived a similar C-index of 0.734 (95% CI: 0.671–0.798) and AUC values of 0.785, 0.778, and 0.767 at 1, 3, and 5 years, respectively. The nomogram demonstrated good calibration in both cohorts, indicating strong agreement between predicted and observed outcomes. The threshold probabilities for DCA at 1-, 3-, and 5-years post-surgery in the training and validation cohorts were 0.08~k0.74, 0.25~0.80, and 0.08~0.89, and 0.13~0.60, 0.28~0.81, and 0.25~0.88, respectively.ConclusionsA nomogram incorporating a Lasso score effectively predicted prognosis in glioma patients. However, its performance did not significantly exceed that of standard clinical nomograms.
Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis
Authors: Chen Lu , Zhou Pengxiang , Li Zhengqian , Wu Ziyang , Zhai Suodi 
Published: January 2025

ObjectiveTo compare the efficacy and safety of pharmaceutical interventions to prevent etomidate-induced myoclonus (EIM), providing the optimal intervention for clinical practice.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to sixth May 2024. We included randomized controlled trials (RCTs) comparing intravenous pharmaceutical interventions to prevent EIM with placebo, no intervention, or another pharmaceutical intervention.ResultsForty-eight RCTs involving 4,768 participants randomly assigned to 20 intravenous pharmaceutical interventions and normal saline were included. Granisetron (odds ratio [OR]: 0.01, 95% confidence interval [CI]: 0.00 to 0.06; one study, moderate certainty) and oxycodone (OR: 0.01, 95% CI: 0.00 to 0.05; three studies, low certainty) was found to be the most effective intervention in reducing the risk of EIM and ranked highest in terms of surface under the cumulative ranking values (94.4% and 89.7% probability), followed by sufentanil (76.5% probability) and remifentanil (74.8% probability). Further subgroup analysis of EIM at mild, moderate-to-severe levels highlighted granisetron and oxycodone as the favorable interventions for reducing EIM. For safety outcomes, the synthesized results indicated that opioids were associated with a higher risk of adverse events (AEs), while no severe AEs were observed.ConclusionModerate-to-low certainty evidence indicated that granisetron and oxycodone may represent the optimal intervention for reducing the risk of overall and moderate-to-severe EIM with a reasonable safety profile, providing the potential interventions for clinical practice.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=291275.
Real-world pharmacovigilance of ofatumumab in multiple sclerosis: a comprehensive FAERS data analysis
Authors: Chen Hui 
Published: January 2025

BackgroundOfatumumab, a fully human monoclonal antibody targeting CD20, is approved for the treatment of relapsing multiple sclerosis. Comprehensive real-world safety data are crucial for informing clinical practice.MethodsThe FDA Adverse Event Reporting System database was utilized to perform a disproportionality analysis, covering reports from Q3 2020 to Q2 2024, in which ofatumumab was identified as the primary suspected drug. Statistical approaches used included the Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. The timing of adverse events was assessed using the Weibull distribution model to highlight temporal risk patterns.ResultsKnown adverse reactions, such as injection site reactions and upper respiratory tract infections, displayed positive signals. Additionally, novel off-label adverse events, including brain fog, muscle spasms, and mood alterations, were identified, marking the first real-world evidence of these potential risks. Temporal analysis revealed that most adverse events occurred within the first month of treatment, indicating an early risk phase. Subgroup analysis demonstrated notable differences in adverse event profiles by gender and age, with males more prone to hyperhidrosis and older patients more susceptible to neurological symptoms.ConclusionThis real-world analysis of ofatumumab provides important safety insights, confirming known adverse reactions and identifying additional potential risks. Early and tailored monitoring protocols during the initial treatment phase, including regular neurological and psychiatric assessments, are recommended to optimize patient safety and outcomes. Prospective studies are recommended to validate these results and explore the underlying mechanisms.
Modified citrus pectin ameliorates methotrexate-induced hepatic and pulmonary toxicity: role of Nrf2, galectin-3/TLR-4/NF-κB/TNF-α and TGF-β signaling pathways
Authors: Ismail Randa , Habib Heba A. , Anter Aliaa F. , Amin Amr , Heeba Gehan H. 
Published: January 2025

IntroductionMethotrexate (MTX) is a frequently utilized anti-inflammatory and anticancer agent. Its potential liver and lung toxicity often limits its clinical effectiveness. We conducted this study to demonstrate the possible protective impacts of a natural galectin-3 (Gal-3) inhibitor, modified citrus pectin (MCP), against MTX-induced liver and lung toxicity and verify the potential signaling pathways of these suggested effects. In vitro, the cytotoxicity of MCP and its modulatory effect on MTX cytotoxic efficacy were assessed.MethodsFour groups of rats were used: control, MTX (40 mg/kg, single intraperitoneal injection on day 9), MTX + MCP (200 mg/kg/day, orally, for 2 weeks), and MCP alone. MCF7, Nalm6, and JEG3 cell lines were used for the in vitro cytotoxicity assay.ResultsMCP counteracted liver and lung toxicity evidenced by ameliorating the markers of liver and lung functions. Moreover, MCP minimized oxidative stress elicited by MTX in lung and liver tissues, as indicated by reduced malondialdehyde levels, elevated levels of reduced glutathione, increased superoxide dismutase activity, and upregulated Nrf2 protein expression. In hepatic and pulmonary tissues, MCP downregulated the inflammatory signaling pathway, Gal-3/TLR-4/NF-κB/TNF-α. MCP pretreatment decreased TGF-β, collagen content, and cleaved caspase-3 levels. MCP enhanced the cytotoxicity of MTX in Nalm6 and JEG3 and did not interfere with its cytotoxicity in the MCF7 cell lines.DiscussionMCP attenuated MTX-induced liver and lung toxicity through antioxidant, anti-fibrotic, anti-inflammatory, and anti-apoptotic influences, as demonstrated by the improved histopathological changes induced by MTX in pulmonary and hepatic tissues. Moreover, it increased MTX cytotoxicity in different human cell lines.
Itraconazole promotes melanoma cells apoptosis via inhibiting hedgehog signaling pathway-mediated autophagy
Authors: Jin Shunqiao , Liu Xiaojiao , Cai Lingqin , Yan Jiayu , Li Ling , Dong Hongjun , Gao Yuxue , Zhu Xicong , Zhang Cong , Xu Xuezhu 
Published: January 2025

BackgroundItraconazole, a widely used antifungal medication, has shown potential in inhibiting tumor growth and reducing angiogenesis. However, its role in melanoma tumor growth remains insufficiently explored. This study investigates the inductive effect of itraconazole on autophagy-mediated apoptosis in melanoma cells.MethodPotential drug targets were identified using the PMF machine learning algorithm. Apoptosis and cell cycle in melanoma cell lines A375 and A2058 were assessed via flow cytometry. Western blot analysis was performed to examine autophagy and associated signaling proteins, while autophagy flux and autophagosome formation were visualized using fluorescence microscopy. A melanoma cell xenograft mouse model was established to evaluate the inhibitory mechanisms of itraconazole on tumor cell proliferation.ResultUsing the PMF machine learning algorithm, SQSTM1 was identified as the primary target of itraconazole. Itraconazole inhibited melanoma cell proliferation by inducing G1 phase arrest and autophagy-mediated apoptosis in A375 and A2058 cells. Furthermore, itraconazole suppressed Hedgehog signaling and counteracted the activation of the Hedgehog agonist recombinant human Sonic Hedgehog (rhShh). In vivo, itraconazole significantly reduced tumor growth in A375 and A2058 xenograft models.ConclusionItraconazole induces autophagy-mediated apoptosis in melanoma cells by inhibiting Hedgehog signaling, underscoring its potential as a therapeutic option for melanoma treatment.
Comparison and verification of detection accuracy for late deceleration with and without uterine contractions signals using convolutional neural networks
Authors: Sato Ikumi , Hirono Yuta , Shima Eiri , Yamamoto Hiroto , Yoshihara Kousuke , Kai Chiharu , Yoshida Akifumi , Uchida Fumikage , Kodama Naoki , Kasai Satoshi 
Published: January 2025

IntroductionCardiotocography (CTG) is used to monitor and evaluate fetal health by recording the fetal heart rate (FHR) and uterine contractions (UC) over time. Among these, the detection of late deceleration (LD), the early marker of fetal mild hypoxemia, is important, and the temporal relationship between FHR and UC is an essential factor in deciphering it. However, there is a problem with UC signals generally tending to have poor signal quality due to defects in installation or obesity in pregnant women. Since obstetricians evaluate potential LD signals only from the FHR signal when the UC signal quality is poor, we hypothesized that LD could be detected by capturing the morphological features of the FHR signal using Artificial Intelligence (AI). Therefore, this study compares models using FHR only (FHR-only model) and FHR with UC (FHR + UC model) constructed using a Convolutional Neural Network (CNN) to examine whether LD could be detected using only the FHR signal.MethodsThe data used to construct the CNN model were obtained from the publicly available CTU-UHB database. We used 86 cases with LDs and 440 cases without LDs from the database, confirmed by expert obstetricians.ResultsThe results showed high accuracy with an area under the curve (AUC) of 0.896 for the FHR-only model and 0.928 for the FHR + UC model. Furthermore, in a validation using 23 cases in which obstetricians judged that the UC signals were poor and the FHR signal had an LD-like morphology, the FHR-only model achieved an AUC of 0.867.ConclusionThis indicates that using only the FHR signal as input to the CNN could detect LDs and potential LDs with high accuracy. These results are expected to improve fetal outcomes by promptly alerting obstetric healthcare providers to signs of nonreassuring fetal status, even when the UC signal quality is poor, and encouraging them to monitor closely and prepare for emergency delivery.
Transcriptomic and metabolomic analyses reveal the mechanism of color difference between two kinds of Cistanche deserticola before and after drying
Authors: Zhu Tiantian , Zhang Jing , Liu Tianle , Zhang Shuai , Yang Baimei , Xu Li , Zhao Lei , Li Mengfei , Jin Ling 
Published: January 2025

IntroductionCistanche deserticola is an important traditional Chinese herbal medicine. The fresh cistanche squamous stem is typically yellow-white and brown after drying. Oil cistanche is a cistanche variant with a purple squamous stem that turns black after drying. The color difference between oil cistanche and cistanche is obvious, and the former has a higher market price. However, the mechanism underlying the color difference of oil cistanche and cistanche remains unclear.MethodsThis study evaluated the total flavone contents in oil cistanche and cistanche and compared the differential metabolites and differentially expressed genes (DEGs) and the contents of iridoid of dried oil cistanche and cistanche samples were determined by high-performance liquid chromatography, and finally the polysaccharides contents of them were determined to comprehensively analyze the formation mechanism of color difference between oil cistanche and cistanche.ResultsThe results showed that the total flavonoid content in oil cistanche was significantly higher than that in cistanche. Metabolomic analysis identified 50 differentially accumulated metabolites (DAMs) (34 up-regulated and 16 down-regulated), including carbohydrates, terpenoids, and flavonoids. Moreover, 3,376 DEGs were selected, among which significant up-regulated of IGS1 and CYP84A1 and down-regulated of 4CLL1, F6H2-2-1 and 5MAT1 genes jointly regulated flavonoid biosynthesis and affected the accumulation of differentially accumulated metabolites. Significant up-regulated of the CCD7 gene affected carotenoid component production, and significant up-regulated of the UGT85A24 gene promoted the accumulation of geniposidic acid. In addition, the contents of iridoid and polysaccharide in oil cistanche were significantly higher than those in cistanche.DiscussionThe differential expression of flavonoids and terpenoid differential metabolites and CYP84A1, 5MAT1, FLS, UGT85A24 and CCD7 mainly caused the purple color of fresh oil cistanche. Dried samples of oil cistanche were darker in color than those of cistanche, due to the higher content of iridoids and polysaccharides in the former. This study preliminarily revealed the causes of the color differences between oil cistanche and cistanche, and provided references for the systematic study of cistanche and its germplasm resources, as well as for the breeding of C. deserticola.
Teachers’ responses to racism and racist bullying in Dutch primary schools
Authors: Sieben-Aduful Karen M. A. , Willems Roy A. , Völlink Trijntje , van der Wiel Nico , Sapouna Maria , de Bruijn Pieter , Blok Gemma , Bos Arjan E. R. , van Lankveld Giel 
Published: January 2025

BackgroundEarly in life, children with a non-White skin color, or a non-Western cultural or religious background, are susceptible of experiencing acts of racism. Since they spend a significant time of their daily life in school, teachers have a crucial role in providing a safe and bias-free environment for these children. However, teachers might find it challenging to react to bullying based on racism.AimThis study aims to investigate teachers’ experiences of and reactions to racist bullying among pupils in primary schools in The Netherlands. Additionally, this study aims to explore how racism is discussed in class.MethodWith nine semi-structured in-depth interviews teachers’ attitudes and reactions toward racist bullying were examined as well as their perceived competence and skills of handling this. In addition, teachers’ availability on tools to discuss racism in class was investigated as well. Data was analyzed using thematic analysis.ResultsThe results show that teachers emphasize a safe class climate but find it challenging addressing racist incidents, for instance determining its severity, or coping with the external influences on pupils’ racist beliefs. Most teachers also expressed to not make a distinction between racist and interpersonal bullying. While teachers expressed that they talked about racism in the classroom, it seemed that they primarily talked about cultural diversity and not racism per se.ConclusionDealing with racism and racist bullying is an important but complicated task for teachers. Providing teachers with appropriate tools to increase knowledge, awareness and skills will help them to understand the negative impact racism has on children. Further, the results implicate that a pro-active approach can stimulate teachers to critically reflect on their own racial identity, and on school methods, teaching resources and policies concerning racism.
Poor sleep quality and associated factors among HIV-positive and negative postpartum women in Addis Ababa, Ethiopia: a comparative cross-sectional study
Authors: Mihertabe Milen , Geremew Alehegn Bishaw , Fentie Elsa Awoke , Rtbey Gidey 
Published: January 2025

BackgroundPoor sleep quality is common during the postpartum period due to nighttime feeding and frequent nocturnal awakenings of infants. In addition, the condition may worsen among postpartum women living with human immunodeficiency virus (HIV), affecting their capacity to care for their child. Therefore, this study will provide baseline information by assessing the burden of poor sleep quality and associated factors among HIV-positive and negative postpartum women in Addis Ababa, Ethiopia.ObjectiveThe aim of this study was to assess poor sleep quality and its associated factors among HIV-positive and negative postpartum women in Addis Ababa, Ethiopia in 2023.MethodsA comparative cross-sectional study was conducted from 20 March to 20 May 2023, and a systematic random sampling technique was employed to obtain a total of 535 study subjects. An interviewer-administered questionnaire and chart review were used to collect the data. The Pittsburgh Sleep Quality Index was used to assess the outcome variable with a cutoff point ≥5. Binary logistic regression was employed to check the association of each independent variable with the outcome variable. Variables having a p-value of less than 0.05 in multivariable analysis were considered statistically significant and an adjusted odds ratio with a 95% confidence interval (CI) was computed.ResultsIn this study, the overall prevalence of poor sleep quality among postpartum women was 56.3% [95% CI (51.9, 60.6)]. Poor sleep quality prevalence among HIV-positive and -negative women was 80% and 50.5%, respectively. Being HIV-positive [AOR = 2.38, 95% CI (1.31, 4.32)], being divorced [AOR = 4.5, 95% CI (1.55, 13)], and having a family history of mental illness [AOR = 1.89, 95% CI (1.16, 3.1)], depression [AOR = 1.93 (1.11, 3.3)], and anxiety [AOR = 2.76, 95% CI (1.8, 4.2)] among postpartum women and poor social support [AOR = 6, 95% CI (1.63, 22.4)] among HIV-positive women were significantly associated with poor sleep quality.Conclusion and recommendationThis study revealed that the prevalence of poor sleep quality was higher among HIV-positive postpartum women compared to HIV-negative women. It would be better if professionals routinely assess postpartum women for sleep quality and focus on HIV-positive women.