bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting transcription factor pu.1 for improving neurologic outcomes after spinal cord injury
Authors: Shi Yi , Zheng Meige , Luo Yang , Li Jianjian , Ouyang Fangru , Zhao Yuanzhe , Wang Jingwen , Ma Zhida , Meng Congpeng , Bi Yihui , Cheng Li , Jing Juehua 
Published: August 2024

BackgroundAfter spinal cord injury (SCI), lipid metabolism dysregulation at the lesion site exacerbates secondary damage. The transcription factor pu.1 has been implicated as a negative regulator of multiple lipid metabolism-related genes and pathways. However, its role in post-SCI lipid metabolism remains unclear.MethodsWe employed a mouse model of complete T10 crush SCI. Non-targeted metabolomics and bioinformatics analysis were utilized to investigate lipid metabolism at the lesion site after SCI. Polarized light imaging was used to evaluate the presence of cholesterol crystals. DB1976, a specific inhibitor of pu.1, was administered to examine its impact on local lipid metabolism after SCI. Immunofluorescence staining was performed to assess pu.1 expression and distribution, and to evaluate lipid droplet formation, astrocytic/fibrotic scar development, inflammatory cell infiltration, and tight junctions within the vasculature.ResultsNon-targeted metabolomics and bioinformatics analyses revealed significant alterations in lipid metabolism components after SCI. Moreover, immunofluorescence staining and polarized light imaging demonstrated substantial BODIPY+ lipid droplet accumulation and persistent cholesterol crystal formation at the lesion site after SCI. Increased pu.1 expression was predominantly observed within macrophages/microglia at the lesion site after SCI. DB1976 treatment significantly mitigated lipid droplet accumulation and cholesterol crystal formation, reduced CD68+ macrophage/microglial infiltration, and attenuated fibrotic scar formation. Moreover, DB1976 treatment promoted the expression of claudin-5 and zonula occludens-1 between vascular endothelial cells and enhanced GFAP+ glial connectivity after SCI.ConclusionOur study reveals a significant correlation between lipid metabolism disturbance post-SCI and transcription factor pu.1 upregulation, specifically in macrophages/microglia at the lesion site. Thus, targeted pu.1 modulation has the potential to yield promising results by substantially diminishing the deposition of lipid metabolism byproducts at the lesion site and fostering a milieu conducive to SCI repair.
Determinants of severe acute malnutrition among under-five children in Ethiopia: analysis using data from the 2016 Ethiopia Demographic and Health Survey
Authors: Areba Abriham Shiferaw , Abame Desta Erkalo , Tirore Lire Lemma , Bubamo Bisrat Feleke 
Published: August 2024

ObjectiveMalnutrition is a silent killer that is under-reported, under-addressed, and, as a result, emphasized. This study aimed to identify the determinants of severe acute malnutrition (SAM) among under-five children in Ethiopia.MethodsCross-sectional data from the 2016 Ethiopian Demographic and Health Survey (EDHS) were used. A total of 6,170 under-five children were included in the current analysis. The data were cleaned and analyzed using STATA 14. An adjusted odds ratio (AOR) and their 95% confidence intervals (CIs) were calculated to determine the association between factors and outcomes. A p-value of less than 0.05 was considered significant in multivariable logistic regression.ResultsA multivariable logistic regression revealed that under-five children with the age of children in months 6–11 (AOR = 1.52, 95% CI: 1.25, 1.86), 12–23 (AOR = 1.98, 95% CI: 1.65, 2.37), and 24–59 months (AOR = 1.71, 95% CI: 1.40, 2.08), birth order between fourth and fifth (AOR = 1.24, 95% CI: 1.01, 1.54), having fever (AOR = 1.31, 95% CI: 1.09, 1.58), anemic children (AOR = 1.21, 95% CI: 1.07, 1.36), age of mothers in years 25–34 (AOR = 0.60, 95% CI: 0.51, 0.72) and 35–49 (AOR = 0.49, 95% CI: 0.39, 0.63), antenatal care (ANC) visits (AOR = 0.83, 95% CI: 0.71, 0.92), rural residence (AOR = 2.98, 95% CI: 2.54, 3.49), and solid fuels users (AOR = 2.46, 95% CI: 1.86, 3.26) were significant predictors.ConclusionOlder age of children, those with higher birth order, those having fever, anemic children, those living in rural areas, and solid fuel users were more likely to suffer from SAM, while older mothers and those having ANC visits had reduced SAM as significant predictors.
Preliminary study on DCE-MRI radiomics analysis for differentiation of HER2-low and HER2-zero breast cancer
Authors: Yin Liang , Zhang Yun , Wei Xi , Shaibu Zakari , Xiang Lingling , Wu Ting , Zhang Qing , Qin Rong , Shan Xiuhong 
Published: August 2024

PurposeThis study aims to evaluate the utility of radiomic features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in distinguishing HER2-low from HER2-zero breast cancer.Patients and methodsWe retrospectively analyzed 118 MRI cases, including 78 HER2-low and 40 HER2-zero patients confirmed by immunohistochemistry or fluorescence in situ hybridization. From each DCE-MRI case, 960 radiomic features were extracted. These features were screened and reduced using intraclass correlation coefficient, Mann-Whitney U test, and least absolute shrinkage to establish rad-scores. Logistic regression (LR) assessed the model’s effectiveness in distinguishing HER2-low from HER2-zero. A clinicopathological MRI characteristic model was constructed using univariate and multivariate analysis, and a nomogram was developed combining rad-scores with significant MRI characteristics. Model performance was evaluated using the receiver operating characteristic (ROC) curve, and clinical benefit was assessed with decision curve analysis.ResultsThe radiomics model, clinical model, and nomogram successfully distinguished between HER2-low and HER2-zero. The radiomics model showed excellent performance, with area under the curve (AUC) values of 0.875 in the training set and 0.845 in the test set, outperforming the clinical model (AUC = 0.691 and 0.672, respectively). HER2 status correlated with increased rad-score and Time Intensity Curve (TIC). The nomogram outperformed both models, with AUC, sensitivity, and specificity values of 0.892, 79.6%, and 82.8% in the training set, and 0.886, 83.3%, and 90.9% in the test set.ConclusionsThe DCE-MRI-based nomogram shows promising potential in differentiating HER2-low from HER2-zero status in breast cancer patients.
To cut or not to cut – that is the question: a comparative analysis of long-term follow-up after complete and incomplete electroconization of the cervix due to high-grade squamous intraepithelial lesion
Authors: Suchońska Barbara E. , Gajewska Małgorzata E. , Blok Joanna M. 
Published: August 2024

IntroductionElectroconization of the uterine cervix (LEEP/LLETZ) is an appropriate and sufficient procedure for high-grade squamous epithelial lesion – HSIL. Negative margins are considered fundamental for confirming the absence of residual disease. Further management after incomplete excision among women who have not completed their procreative plans is difficult because subsequent cervical procedures may cause issues with carrying a pregnancy to term. Since almost one-third of the untreated patients with HSIL will develop cervical carcinoma, it is essential to balance the desire to radicalize treatment with its obstetric consequences. We compared the further clinical course of the patients after complete and incomplete procedures to observe whether completeness of excision is necessary for a successful outcome. We aim to identify risk factors that influence persistent or recurrent HSIL.MethodsThe study has comprised 781 patients aged 18-85 – the research group was composed of 140 (17.93%) patients after incomplete conization and the control group of 641 (82.17%) patients after the complete one. Patients were scheduled for follow-up examinations every 6 months – including cytology, HPV typing, and colposcopy with tissue sampling. The Chi-square test or Fisher’s exact test was performed as a tool for group comparisons for variables on the qualitative scale. Univariable and multivariable logistic regression models have been used to determine factors associated with the risk of persistent or recurrent HSIL. To evaluate the discriminatory ability of the logistic regression models, the Area Under the Curve (AUC) was calculated.ResultsThe statistical analysis results don’t indicate a statistical significance between the frequency of HSIL in groups. HPV infection has increased the risk of persistent/recurrent lesions by 38 times, constituting the most important factor.DiscussionClose follow-up instead of inconsiderate repeat procedures should be taken under consideration among patients of reproductive age after incomplete conization of the cervix. HPV typing may be an essential method to predict recurrent cervical dysplasia. Promoting HPV typing and vaccination can reduce the number of invasive procedures and improve quality of life and obstetrics outcomes.
Understanding the impact of radiotherapy fractionation on overall survival in a large head and neck squamous cell carcinoma dataset: a comprehensive approach combining mechanistic and machine learning models
Authors: Shuryak Igor , Wang Eric , Brenner David J. 
Published: August 2024

IntroductionTreating head and neck squamous cell carcinomas (HNSCC), especially human papillomavirus negative (HPV-) and locally advanced cases, remains difficult. Our previous analyses of radiotherapy-only HNSCC clinical trials data using mechanistically-motivated models of tumor repopulation and killing by radiotherapy predicted that hyperfractionation with twice-daily fractions, or hypofractionation involving increased doses/fraction and reduced treatment durations, both improve tumor control and reduce late normal tissue toxicity, compared with standard protocols using 35×2 Gy. Here we further investigated the validity of these conclusions by analyzing a large modern dataset on 3,346 HNSCC radiotherapy patients from the University Health Network in Toronto, Canada, where 42.5% of patients were also treated with chemotherapy.MethodsWe used a two-step approach that combines mechanistic modeling concepts with state-of-the-art machine learning, beginning with Random Survival Forests (RSF) for an exploratory analysis and followed by Causal Survival Forests (CSF) for a focused causal analysis. The mechanistic concept of biologically effective dose (BED) was implemented for the standard dose-independent (DI) tumor repopulation model, our alternative dose-dependent (DD) repopulation model, and a simple model with no repopulation (BEDsimp). These BED variants were included in the RSF model, along with age, stage, HPV status and other relevant variables, to predict patient overall survival (OS) and cause-specific mortality (deaths from the index cancer, other cancers or other causes).ResultsModel interpretation using Shapley Additive Explanations (SHAP) values and correlation matrices showed that high values of BEDDD or BEDDI, but not BEDsimp, were associated with decreased patient mortality. Targeted causal inference analyses were then performed using CSF to estimate the causal effect of each BED variant on OS. They revealed that high BEDDD (&gt;61.8 Gy) or BEDDI (&gt;57.6 Gy), but not BEDsimp, increased patient restricted mean survival time (RMST) by 0.5-1.0 years and increased survival probability (SP) by 5-15% several years after treatment. In addition to population-level averages, CSF generated individual-level causal effect estimates for each patient, facilitating personalized medicine.DiscussionThese findings are generally consistent with those of our previous mechanistic modeling, implying the potential benefits of altered radiotherapy fractionation schemes (e.g. 25×2.4 Gy, 20×2.75 Gy, 18×3.0 Gy) which increase BEDDD and BEDDI and counteract tumor repopulation more effectively than standard fractionation. Such regimens may represent potentially useful hypofractionated options for treating HNSCC.
Effects of dance sports exercise on vestibular function and balance of children with sensorineural hearing loss; a randomized quasi-experimental trial
Authors: Hu Fang , Qiu Xuan , Wu Xinbo , Wu Xilong , Li Han , Kim Sukwon 
Published: August 2024

BackgroundSensorineural hearing loss (SNHL) children have difficulty living and limited movement due to impaired vestibular function and reduced balance ability.ObjectivesThe present study evaluated the effects of Latin dance training on the vestibular function and balance of SNHL children.MethodsThirty SNHL children with no difference in vestibular function and balance ability were randomly divided into two groups, the Latin dance training group (LTG, n = 15) and the control group (CONG, n = 15). Vestibular function, timed eyes-closed static (ECS) and functional reach test (FRT) were measured before and after the intervention, and a two-way repeated-measures analysis of variance was performed.ResultsAfter training, the vestibular function performance of LTG was higher than that of CONG (CONG: 16.425 ± 3.616 vs. LTG: 12.241 ± 2.610, p = 0.0411, ES = 1.3914), the left foot ECS performance of LTG was higher than that of CONG (CONG: 2.765 ± 0.872 vs. LTG: 4.688 ± 1.113, p = 0.0026, ES = 1.9857), the right foot ECS performance of LTG was higher than that of CONG (CONG: 3.113 ± 0.639 vs. LTG: 4.797 ± 1.071, p = 0.0137, ES = 2.01), the FRT performance of LTG was higher than that of CONG (CONG: 32.009 ± 6.134 vs. LTG: 43.797 ± 6.616, p = 0.0021, ES = 1.9135).ConclusionsAfter Latin dance training, SNHL children improved vestibular function and balance. The static balance ability of the left foot has been improved significantly than right foot.
Timing of menarche and pubertal growth patterns using the QEPS growth model
Authors: Gårdstedt-Berghog Jenni , Niklasson Aimon , Sjöberg Agneta , Aronson A. Stefan , Pivodic Aldina , Nierop Andreas F. M. , Albertsson-Wikland Kerstin , Holmgren Anton 
Published: August 2024

ObjectivesTo explore the timing of menarche, postmenarcheal growth, and to investigate the impact of various variables on menarcheal age and postmenarcheal and pubertal growth.Study DesignThis longitudinal community population-based study analyzed pubertal growth and menarcheal age in 793 healthy term-born Swedish girls, a subset of the GrowUp1990Gothenburg cohort. The timing of menarche and postmenarcheal growth was related to variables from the Quadratic-Exponential-Pubertal-Stop (QEPS) growth model, birth characteristics, and parental height. Multivariable models were constructed for clinical milestones; at birth, age 7 years, pubertal growth onset, and midpuberty.ResultsMenarche aligned with 71.6% (18.8) of the QEPS model's specific pubertal growth function, at a mean age of 13.0 (1.3) years, ranging from 8.2 to 17.2 years. Postmenarcheal growth averaged 8.0 (4.9) cm, varying widely from 0.2 to 31.1 cm, decreasing with later menarche. Significant factors associated with menarcheal age included height at 7 years, childhood body-mass index, parental height, and QEPS-derived pubertal growth variables. Multivariable models demonstrated increasing explanatory power for each milestone, explaining 1% of the variance in menarcheal age at birth, 8% at age 7 years, 44% at onset of pubertal growth, and 45% at midpuberty.ConclusionsThis study underscores the strong link between pubertal growth and age at menarche. Data available at start of puberty explain 44% of the variation in menarcheal age, apparent on average 3.2 years before menarche. In addition, the study shows a previously seldom noticed wide variation in postmenarcheal height gain from 0.2 to 31.1 cm.
Unveiling the therapeutic potential of Lobaria extract and its depsides/depsidones in combatting Aβ42 peptides aggregation and neurotoxicity in Alzheimer’s disease
Authors: Yang Meixia , Yan Caishan , Ospondpant Dusadee , Wang Lisong , Lin Shengying , Tang Wai Lun , Dong Tina Tingxia , Tong Penger , Xu Qin , Tsim Karl Wah Keung 
Published: August 2024

Background: The development of effective inhibitors that can inhibit amyloid β (Aβ) peptides aggregation and promote neurite outgrowth is crucial for the possible treatment of Alzheimer’s disease (AD). Lobaria (Schreb.) Hoffm., a traditional Chinese medicine used in Himalaya region for inflammatory diseases, contains depsides/depsidones (DEPs) such as gyrophoric acid, norstictic acid, and stictic acid known for their anti-cancer and anti-inflammation properties.Methods:Lobaria extracts were analyzed using HPLC to identify DEPs and establish standards. The inhibitory effects of Lobaria on Aβ42 fibrillization and depolymerization were assessed using various approaches with biophysical and cellular methods. The neuroprotective activity of Lobaria extracts and its DEPs aganist Aβ-mediated cytotoxicity was also evaluated.Results: Norstictic and stictic acid were found in the water extract, while norstictic, stictic, and gyrophoric acid were detected in the ethanol extract of Lobaria. Both extracts, and their DEPs effectively inhibited Aβ42 fibrillation and disaggregate mature Aβ42 fibrils. Notably, the ethanol extract showed superior inhibitory effect compared to the water extract, with gyrophoric acid being the most effective DEPs. Additionally, herbal extract-treated Aβ42 aggregation species significantly protected neuronal cells from Aβ42-induced cell damage and promoted neurite outgrowth.Conclusion: This study is the first to investigate the effect of Lobaria on Aβ42 and neuronal cell in AD. Given that Lobaria is commonly used in ethnic medicine and food with good safety records, our findings propose that Lobaria extracts and DEPs have potential as neuroprotective and therapeutic agents for AD patients.
PepT1-targeted nanodrug based on co-assembly of anti-inflammatory peptide and immunosuppressant for combined treatment of acute and chronic DSS-induced ColitiS
Authors: Zhang Daifang , Jiang Longqi , Yu Fengxu , Yan Pijun , Liu Yong , Wu Ya , Yang Xi 
Published: August 2024

IntroductionInflammatory bowel disease (IBD), as a chronic and recurrent inflammatory bowel diseases with limited therapeutic outcomes, is characterized by immune disorders and intestinal barrier dysfunction. Currently, the most medications used to cure IBD in clinic just temporarily induce and maintain remission with poor response rates and limited outcomes. Therefore, it is urgently necessary to develop an appropriate therapeutic candidate with preferable efficacy and less adverse reaction for curing IBD.MethodsFive groups of mice were utilized: control that received saline, DSS group (mice received 2.5% DSS or 4% DSS), KPV group (mice received KPV), FK506 group (mice received FK506) and NPs groups (mice received NPs). The effect of NP on the inflammatory factors of macrophage was evaluated using CCK-8, quantitative polymerase chain reaction (PCR), Elisa and Western blot (WB). Immunofluorescent staining revealed the targeting relationship between NP and Petp-1. Immunohistochemistry staining showed the effect of NP on tight junction proteins. Moreover, in vivo animal experiments confirmed that NPs reduced inflammatory levels in IBD.Results and DiscussionAfter administering with NPs, mice with DSS-induced acute or chronic colitis exhibited significant improvement in body weight, colon length, and disease activity index, decreased the level of the factors associated with oxidative stress (MPO, NO and ROS) and the inflammatory cytokines (TNF-α, IL-1β and IL-6), which implied that NPs could ameliorate murine colitis effectively. Furthermore, treating by NPs revealed a notable reduction of the expressions of CD68 and CD3, restoring the expression levels of tight junction proteins (Claudin-5, Occludin-1, and ZO-1) were significantly restored, surpassing those observed in the KPV and FK506 groups. which indicated that NPs can reduce inflammation and enhance epithelial barrier integrity by decreasing the infiltration of macrophages and T-lymphocytes. Collectively, those results demonstrated the effectively therapeutic outcome after using NPs in both acute and chronic colitis, suggesting that the newly co-assembled of NPs can be as a potential therapeutic candidate for colitis.
Case report: Lichenoid eruption under immunotherapy with MK-4830 and pembrolizumab in a breast cancer patient
Authors: Kachlik Zofia , Błażewicz Izabela , Ciarka Aleksandra , Nowicki Roman J. 
Published: August 2024

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet they can induce immune-related adverse events (irAEs), including cutaneous toxicities such as lichenoid eruptions. Pembrolizumab, a PD-1 inhibitor, is known for its association with lichen-planus-like reactions, while the side effect profile of combining immunotherapy with MK-4830, a novel fully human IgG4 monoclonal antibody that targets ILT-4, remains limited.Case reportWe present a case of a 47-year-old female with metastatic breast cancer who developed a grade 2 Common Terminology Criteria for Adverse Events (CTCAE) lichenoid reaction after 9 months of MK-4830 and pembrolizumab use. Confluent, erythematous papules with Wickham’s striae appeared predominantly on the extremities. Initial therapy with high-potency topical corticosteroids proved insufficient, however prednisone 40 mg daily resulted in satisfactory remission of lichen-planus-like reaction, permitting continued immunotherapy without dosage adjustment.ConclusionThis case highlights the novel occurrence of lichenoid eruption induced by MK-4830 and pembrolizumab in breast cancer treatment. The patient was successfully treated with oral prednisone, which controlled the skin symptoms without interrupting ICI therapy. We emphasize that early diagnosis and treatment of low-grade lichenoid eruption can prevent the cessation of ICIs, thereby combining the benefits of managing irAEs and avoiding cancer progression, leading to a better long-term prognosis.