bluuebunny/crossref_metadata_2025_split huggingface dataset:
Etoposide, cisplatin, and sintilimab combined with anlotinib in successful treatment of adrenocortical carcinoma with lung metastasis: a case report
Authors: Niu Wenjing , Zhang Haimei , Ma Xuezhen , Liang Hua , Qiao Zhongshi , Wang Zheng , Niu Lifeng 
Published: August 2024

BackgroundAdrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC.Case presentationWe report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient’s lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism.ConclusionThis case highlights the remarkable response of our patient’s ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.
Racial/ethnic differences in the clinical presentation and survival of breast cancer by subtype
Authors: Nhim Vutha , Bencomo-Alvarez Alfonso E. , Alvarado Luis , Kilcoyne Michelle , Gonzalez-Henry Mayra A. , Olivas Idaly M. , Keivan Mehrshad , Gaur Sumit , Mulla Zuber D. , Dwivedi Alok K. , Gadad Shrikanth S. , Eiring Anna M. 
Published: August 2024

BackgroundBreast cancer (BC) affects racial and ethnic groups differently, leading to disparities in clinical presentation and outcomes. It is unclear how Hispanic ethnicity affects BC outcomes based on geographic location and proximity to the United States (U.S.)/Mexico border. We hypothesized that the impact of race/ethnicity on BC outcomes depends on geographic location and country of origin within each BC subtype.MethodsWe analyzed BC data from the Texas Cancer Registry by race/ethnicity/birthplace according to BC subtype (luminal A/luminal B/human epidermal growth factor receptor 2 [HER2]/triple-negative breast cancer[TNBC]). Other covariates included age, geographic location (U.S., Mexico), residency (border, non-border), treatments, and comorbidities. Crude and adjusted effects of race/ethnicity and birthplace on overall survival (OS) were analyzed using Cox regression methods.ResultsOur analysis of 76,310 patient records with specific BC subtypes revealed that Hispanic and non-Hispanic Black (NHB) patients were diagnosed at a younger age compared with non-Hispanic White (NHW) patients for all BC subtypes. For the 19,748 BC patients with complete data on race/ethnicity/birthplace/residency, Hispanic patients had a higher mortality risk in the Luminal A subtype, regardless of birthplace, whereas U.S.-born Hispanics had a higher risk of death in the TNBC subtype. In contrast, NHB patients had a higher mortality risk in the Luminal A and HER2 subtypes. Residence along the U.S./Mexico border had little impact on OS, with better outcomes in Luminal A patients and worse outcomes in Luminal B patients aged 60–74 years.ConclusionRace/ethnicity, geographic birth location, and residency were significant predictors of survival in BC. Migration, acculturation, and reduced healthcare access may contribute to outcome differences.
Sonographic features of uterine fibroids that predict the ablation rate and efficacy of high-intensity focused ultrasound
Authors: Xue Hailan , Wu Songsong , Xiao Kunhong , Ding Guisheng , Chen Sheng 
Published: August 2024

ObjectiveThis study aimed to identify the sonographic indicators that predict the ablation rate and efficiency of uterine fibroids during high-intensity focused ultrasound (HIFU) treatment.MethodsIn this retrospective study, we analyzed the clinical data of patients with uterine fibroids who underwent HIFU treatment at Fujian Provincial Hospital between April 2019 and April 2022. Routine abdominal ultrasound examinations were performed to observe potential indicators before the HIFU treatment. After the treatment, enhanced magnetic resonance imaging (MRI) examination was performed within 2 weeks. The fibroid and non-perfused volumes (NPV) were determined, and the ablation rate and energy efficiency factor (EEF) were calculated.ResultsA total of 75 patients (124 uterine fibroids) were included in this study. Uterine fibroids with a larger volume, high echogenicity, elliptical/diffuse leaf shape, and a posterior attenuation band had a higher HIFU ablation rate (p&lt;0.05). Uterine fibroids with a larger volume and high echogenicity and without necrotic areas had a lower EEF (p&lt;0.05). Multiple comparisons between fibroid types revealed statistically significant differences in EEF between subserosal and submucosal fibroids (p &lt; 0.05) and between subserosal and mixed-type fibroids (p &lt; 0.05). However, no statistically significant difference was observed between mixed-type and submucosal fibroids. The HIFU ablation rate and EEF showed no significant differences based on location within the wall and blood flow within the fibroids.ConclusionSonographic features of uterine fibroids can predict the rate and efficiency of HIFU ablation, providing useful guidance in selecting appropriate treatment for patients.
Case Report: resolution of refractory seizures after neurosurgical intervention in newborns with cerebral extra-axial hemorrhages
Authors: Rohaert C. , Spoor J. K. H. , Dremmen M. , van Hengel-Jacobs A. M. , Smit L. S. , Knol R. 
Published: August 2024

IntroductionIntracranial hemorrhage is a significant cause of neurological damage in newborns. Extra-axial hemorrhages with intraparenchymal extension can precipitate acute clinical deterioration. Seizures are one of the presenting symptoms, which can be refractory to treatment. These hemorrhages can result in considerable long-term morbidity and mortality.AimThe objective of this report was to present three cases of extra-axial hemorrhages in neonates, all exhibiting refractory seizures that resolved after neurosurgical intervention. In addition, a review of literature is provided.MethodsData collected included clinical history, laboratory findings, neuroimaging studies, type of neurosurgical intervention, and patient outcome. All infants presented with extra-axial hemorrhages along with clinical and radiological signs of increased intracranial pressure within the first 6 days of life. These manifestations included a decreased level of consciousness, hypertension, bradycardia, and cerebral midline shift on imaging. Refractory seizures were present in all cases. Urgent magnetic resonance imaging was performed followed by neurosurgical intervention (two needle aspirations, one cranial trepanation), leading to amelioration of clinical symptoms and complete resolution of seizures. Follow-up outcomes included normal psychomotor development in one infant, mild cerebral paresis in another, and delayed motor development in the third. None of the infants developed epilepsy.ConclusionThis study underscores the critical importance of monitoring seizure activity, conducting urgent and appropriate imaging, and implementing targeted neurosurgical intervention, preferably through minimally invasive methods such as percutaneous needle aspiration. Clinicians should be aware of this clinical picture and respond promptly to mitigate neurological damage.
Clinical characteristics, treatment and prognosis of children with SARS-CoV-2 infection complicated with severe neurological dysfunctions in Foshan, China
Authors: Chen Xiaoqian , Liang Yongqi , Jiang Suhua 
Published: August 2024

ObjectiveTo analyze the clinical characteristics, treatment, and prognosis of children infected with SARS-CoV-2 following the adjustment of COVID-19 prevention and control policies in China in December 2022.MethodsA retrospective study was conducted on 9 cases of severe neurological dysfunction caused by SARS-CoV-2 infection in children admitted to Foshan First People's Hospital from December 17 to 31, 2022.ResultsAmong the 9 cases, 7 (71.43%) were under 3 years old, and 2 (22.2%) were over 3 years old with underlying diseases. All patients presented with fever and neurological symptoms such as consciousness disturbance and/or convulsions, and their conditions deteriorated rapidly within 24 h after the onset of fever, without respiratory symptoms. Levels of IL-6, LDH, and d-dimer were significantly elevated. Five cases died within 48 h of admission, one case died after 7 days of treatment due to secondary bacterial infection, and three cases survived for more than 48 h after the initial rescue. All patients developed rapid shock, and five cases experienced multi-organ failure within a short period. In terms of treatment, glucocorticoids were used in 5 cases, intravenous immunoglobulin (IVIG) in 3 cases, and blood purification and tocilizumab in 2 cases.ConclusionSARS-CoV-2 infection in children can lead to severe neurological damage. High fever, convulsions, and inflammatory factors serve as early warning indicators. Glucocorticoids, immunoglobulins, blood purification, and tocilizumab may have some therapeutic effects, but further research is needed to confirm the efficacy.
A simple HPLC–MS/MS method for the determination of polymyxin B in human plasma and its application in the pharmacokinetic study in elderly patients infected with multidrug-resistant Gram-negative bacteria
Authors: Hu Sheng , Guo Nan , Zeng Juan , Li Yue , Zhang Yahui , Jiang Jinjiao , Leng Bing , Shen Chengwu 
Published: August 2024

Introduction: Polymyxin B is widely used to treat infections caused by multidrug-resistant Gram-negative bacteria. However, the pharmacokinetic study data of PB in the elderly are scarce. Herein, a simple method to measure the concentration of PB in human plasma was developed and validated by high performance liquid chromatography—tandem mass spectrometry, and it was applied to a PK study in the elderly.Methods: PB was extracted from human plasma by a rapid protein-precipitation method using 0.1% formic acid in methanol and then separated on an ultimate AQ-C18 column using linear gradient elution with a 0.5-mL/min flow rate. Subsequently, PB was detected using a mass spectrometer operated in positive-ion and multiple-reaction-monitoring modes.Results: The lower limits of quantification of the method for Polymyxin B1 and Polymyxin B2 were 1.00 and 0.10 μg/mL, respectively. The linear ranges for PB1 and PB2 were 1.00–20.02 and 0.10–2.04 μg/mL, respectively. Patients receiving a 75-mg maintenance dose every 12h had AUCss, 24 h, and Css, av values of 117.70 ± 37.03 μg h/mL and 4.14 ± 1.74 μg/mL, respectively. For patients receiving a 100 mg maintenance dose, these values were 152.73 ± 70.09 μg h/mL and 5.43 ± 2.85 μg/mL, respectively.Conclusion: The validated HPLC–MS/MS method was successfully applied to a study on the pharmacokinetics of PB in elderly patients infected with multidrug-resistant Gram-negative bacteria. Both two dose strategies in this study would have a excessive PB exposure in the elderly patients then the therapeutic window recommended by guidelines.
Protective effects of Ganoderma lucidum spores on estradiol benzoate-induced TEC apoptosis and compromised double-positive thymocyte development
Authors: Yang Jihong , Pan Haitao , Wang Mengyao , Li Anyao , Zhang Guoliang , Fan Xiaohui , Li Zhenhao 
Published: August 2024

Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.Methods: In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice.Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4+ T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4+ iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced upregulation of Abpob and Apoa4, curbing the clearance of CD4+Abpob+ and CD4+Apoa4+ T cells by mTECs, resulting in enhanced CD4+ T cell output.Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS’s immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.
Bioinformatic analysis of hippocampal histopathology in Alzheimer’s disease and the therapeutic effects of active components of traditional Chinese medicine
Authors: Zhiyan Chen , Min Zhan , Yida Du , Chunying He , Xiaohua Hu , Yutong Li , Huan Wang , Linjuan Sun 
Published: August 2024

Background and aimPathological changes in the central nervous system (CNS) begin before the clinical symptoms of Alzheimer’s Disease (AD) manifest, with the hippocampus being one of the first affected structures. Current treatments fail to alter AD progression. Traditional Chinese medicine (TCM) has shown potential in improving AD pathology through multi-target mechanisms. This study investigates pathological changes in AD hippocampal tissue and explores TCM active components that may alleviate these changes.MethodsGSE5281 and GSE173955 datasets were downloaded from GEO and normalized to identify differentially expressed genes (DEGs). Key functional modules and hub genes were analyzed using Cytoscape and R. Active TCM components were identified from literature and the Pharmacopoeia of the People’s Republic of China. Enrichment analyses were performed on target genes overlapping with DEGs.ResultFrom the datasets, 76 upregulated and 363 downregulated genes were identified. Hub genes included SLAMF, CD34, ELN (upregulated) and ATP5F1B, VDAC1, VDAC2, HSPA8, ATP5F1C, PDHA1, UBB, SNCA, YWHAZ, PGK1 (downregulated). Literature review identified 33 active components from 23 herbal medicines. Target gene enrichment and analysis were performed for six components: dihydroartemisinin, berberine, naringenin, calycosin, echinacoside, and icariside II.ConclusionMitochondrial to synaptic vesicle dysfunction pathways were enriched in downregulated genes. Despite downregulation, UBB and SNCA proteins accumulate in AD brains. TCM studies suggest curcumin and echinacoside may improve hippocampal pathology and cognitive impairment in AD. Further investigation into their mechanisms is needed.
Novel therapeutic targets for primary open-angle glaucoma identified through multicenter proteome-wide mendelian randomization
Authors: Yuan Weichen , Li Jun , Gao Shang , Sun Wei , Zhao Fangkun 
Published: August 2024

BackgroundThis study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG).MethodsThe summary-data-based Mendelian randomization (SMR) method was used to evaluate the genetic association between plasma proteins and POAG. Two sets of plasma protein quantitative trait loci (pQTLs) data considered exposures were obtained from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. The summary-level genome-wide association studies data for POAG were extracted from the latest Round 10 release of the FinnGen consortium (8,530 cases and 391,275 controls) and the UK Biobank (4,737 cases and 458,196 controls). Colocalization analysis was used to screen out pQTLs that share the same variant with POAG as drug targets identified. The two-sample Mendelian randomization, reverse causality testing and phenotype scanning were performed to further validate the main findings. Protein-protein interaction, pathway enrichment analysis and druggability assessment were conducted to determine whether the identified plasma proteins have potential as drug targets.ResultsAfter systematic analysis, this study identified eight circulating proteins as potential therapeutic targets for POAG. Three causal proteins with strong evidence of colocalization, ROBO1 (OR = 1.38, p = 1.48 × 10−4, PPH4 = 0.865), FOXO3 (OR = 0.35, p = 4.34 × 10−3, PPH4 = 0.796), ITIH3 (OR = 0.89, p = 2.76 × 10−4, PPH4 = 0.767), were considered tier one targets. Five proteins with medium support evidence of colocalization, NCR1 (OR = 1.25, p = 4.18 × 10−4, PPH4 = 0.682), NID1 (OR = 1.38, p = 1.54 × 10−3, PPH4 = 0.664), TIMP3 (OR = 0.91, p = 4.01 × 10−5, PPH4 = 0.659), SERPINF1 (OR = 0.81, p = 2.77 × 10−4, PPH4 = 0.59), OXT (OR = 1.17, p = 9.51 × 10−4, PPH4 = 0.526), were classified as tier two targets. Additional sensitivity analyses further validated the robustness and directionality of these findings. According to druggability assessment, Pimagedine, Resveratrol, Syringaresinol and Clozapine may potentially be important in the development of new anti-glaucoma agents.ConclusionOur integrated study identified eight potential associated proteins for POAG. These proteins play important roles in neuroprotection, extracellular matrix regulation and oxidative stress. Therefore, they have promising potential as therapeutic targets to combat POAG.
Recent approaches of antibody therapeutics in androgenetic alopecia
Authors: Jin Su-Eon , Kim Jino , Sung Jong-Hyuk 
Published: August 2024

Therapeutic antibodies (Abs) have been anticipated as promising alternatives to conventional treatments such as topical minoxidil and oral finasteride for androgenetic alopecia (AGA). Due to the high molecular weight of typical Abs, the half-life of subcutaneous Abs exceeds 2 weeks, allowing an administration intervals of once a month or longer. Direct injection into the areas of hair loss is also feasible, potentially enhancing treatment efficacy while minimizing systemic side effects. However, therapeutic Abs are rarely developed for AGA therapy due to the requirement to be responsiveness to androgens and to exist in the extracellular fluid or cell surface surrounding the hair follicle. In this review, we introduce recent progress of antibody therapeutics in AGA targeting the prolactin receptor, Interleukin-6 receptor, C-X-C motif chemokine ligand 12, and dickkopf 1. As therapeutic Abs for AGA are still in the early stages, targets need further validation and optimization for clinical application.
Sonchus asper (L.) Hill extracts: phytochemical characterization and exploitation of its biological activities by loading into nanoformulation
Authors: Parisi Valentina , Santoro Valentina , Faraone Immacolata , Benedetto Nadia , Vassallo Antonio , De Tommasi Nunziatina , Milella Luigi , Nesticò Antonio , Maselli Gabriella , Fadda Anna Maria , Caddeo Carla 
Published: August 2024

IntroductionThe current investigation presents a two-fold approach to rediscovering the potential of Sonchus asper as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of S. asper, thus enhancing economic profits.MethodsLiquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves. The antioxidant activity, the hypoglycaemic effect and the incorporation into liposomes were evaluated.Results38 compounds and 6 essential amino acids were identified. The incorporation into liposomes maximized the health-promoting properties for potential pharmaceutical or food applications.DiscussionThe commercialization of S. asper could: (i) contribute to improving the well-being of rural and urban communities, being S. asper a wild edible plant available at low cost, environmentally friendly, resilient, and adaptable; (ii) generate landowner economic returns.
A visual pollination mechanism of a new specialized pollinating weevil-plant reciprocity system
Authors: Yue Jianjun , Yan Zhen , Liu Wei , Liu Ju , Yang Depo 
Published: August 2024

IntroductionPollinating flower-consuming mutualisms are considered exemplary models for studying coevolution due to their rarity. Visual cues are considered to have a major role in facilitating the evolution of floral patterns in these systems. We present a new specialized pollinating flower-consuming mutualism from the plant Wurfbainia villosa, which is a traditional Chinese herbal medicine, by a pollinating weevil, Xenysmoderes sp.MethodsIn this study, We utilized monochrome plates for binary-choice tests to determine weevil color preferences, conducted behavioral choice experiments, using trackballs, photographed flowers and weevils, and employed blue sticky boards to attract weevils in the field.ResultsTests were conducted using colorpreferring weevils in both indoor and outdoor field systems, and validation experiments were performed. Behavioral tests were conducted to investigate the role of the visual cues in the pollinator attraction of W. villosa, which is a selfcompatible insect-pollinated plant that relies primarily on the Xenysmoderes sp. weevil for pollination due to its specialized gynandrium-like structure. Behavioral tests demonstrated that a blue color wavelength of 480 nm and the blue color system, as along with the UV-style pattern of the flowers, particularly the parts with specialized gynandrium-like structures in the labellum, were significantly attractive to both male and female weevils. These results were further confirmed through the field blue sticky board trap method.DiscussionThese findings indicated that the interaction between W. villosa and Xenysmoderes sp. weevil was a novel symbiotic relationship involving pollinator flower consumption. Additionally, Wurfbainia villosa flowers developed specific visual cues of UV patterns and specialized structures that played a crucial role in attracting pollinators.