bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy
Authors: Uffenorde Julia , Hariri Mehran , Papalanis Eleftherios , Staffas Annika , Berg Josefine , Stenerlöw Bo , Berglund Hanna , Malmberg Christer , Spiegelberg Diana 
Published: January 2025

BackgroundGlioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity and mortality rates, even with current standard treatments such as surgery, radiation therapy, and chemotherapy. Therefore, there is a pressing need for new therapeutic strategies to improve survival and reduce treatment side effects. In this study, we investigated the effect of HSP90 inhibition in combination with radiotherapy in established and patient-derived glioblastoma cell lines.MethodsPotential radiosensitizing effects of the HSP90 inhibitor Onalespib were studied in XTT and clonogenic survival assays as well as in tumor-mimicking multicellular spheroid models. Further, migration capacity and effects on protein expression were studied after exposure to Onalespib and radiation using Proximity Extension Assay analysis.ResultsHSP90 inhibition with Onalespib synergistically enhanced the radiosensitivity of glioblastoma cells grown in 2D and 3D models, resulting in increased cell death, reduced migration capacity and activation of the apoptotic signaling pathway. The proteomic analysis of glioblastoma cells treated with Onalespib, radiation, and their combination revealed significant alterations in protein expression profiles, involved in growth signaling, immune modulation pathways and angiogenesis. Moreover, the combination treatment indicated potential for enhancing cell cycle arrest and apoptosis, suggesting promising anti-tumor effects.ConclusionThese findings demonstrate that HSP90 inhibition may be a promising strategy to enhance the efficacy of radiotherapy in the treatment of GBM, potentially leading to improved outcomes for patients battling this challenging disease.
Understanding cellular proliferation activity in breast cancer using multi-compartment model of transverse relaxation time mapping on 3T MRI
Authors: Nkonde Kangwa Alex , Cheung Sai Man , Senn Nicholas , He Jiabao 
Published: January 2025

IntroductionPrecise understanding of proliferative activity in breast cancer holds significant value in the monitoring of neoadjuvant treatment, while current immunostaining of Ki-67 from biopsy or resected tumour suffers from partial sampling error. Multi-compartment model of transverse relaxation time has been proposed to differentiate intra- and extra-cellular space and biochemical environment but susceptible to noise, with recent development of Bayesian algorithm suggested to improve robustness. We hence hypothesise that intra- and extra-cellular transverse relaxation times using Bayesian algorithm might be sensitive to proliferative activity.Materials and methodsTwenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma were scanned on a 3 T clinical scanner. The overall transverse relaxation time was computed using a single-compartment model with the non-linear least squares algorithm, while intra- and extra-cellular transverse relaxation times were computed using a multi-compartment model with the Bayesian algorithm. Immunostaining of Ki-67 was conducted, yielding 9 and 11 cases with high and low proliferating activities respectively.ResultsFor single-compartment model, there was a significant higher overall transverse relaxation time (p = 0.031) in high (83.55 ± 7.38 ms) against low (73.30 ± 11.30 ms) proliferating tumours. For multi-compartment model, there was a significant higher intra-cellular transverse relaxation time (p = 0.047) in high (73.52 ± 10.92 ms) against low (61.30 ± 14.01 ms) proliferating tumours. There was no significant difference in extra-cellular transverse relaxation time (p = 0.203) between high and low proliferating tumours.ConclusionsOverall and Bayesian intra-cellular transverse relaxation times are associated with proliferative activities in breast tumours, potentially serving as a non-invasive imaging marker for neoadjuvant treatment monitoring.
Diffuse panbronchiolitis as a rare complication of thymectomy and radiation therapy in a patient with thymoma: a case report
Authors: Lu Ye , Qi Qi , Qu Dan , Chen Yu 
Published: January 2025

BackgroundDiffuse panbronchiolitis (DPB) is an uncommon respiratory disorder characterized by the presence of respiratory bronchiolitis and persistent inflammation in adjacent tissues, which can be effectively treated with early diagnosis and intervention. DPB is a rare complication associated with thymoma that remains poorly understood, especially when it occurs in conjunction with acquired cellular immune deficiency.Case presentationWe present a case of DPB in a patient with thymoma following thymectomy and radiation therapy. A 47-year-old Chinese man underwent thymectomy due to the presence of a mediastinal mass, and pathological examination confirmed a type B2 thymoma. He also underwent 25 sessions of radiation therapy. The patient’s respiratory symptoms, including cough, expectoration, and shortness of breath, worsened significantly after radiation treatment. Immune dysfunction, marked by CD4+ T cell immunodeficiency with normal immunoglobulin levels, was observed. Chest computed tomography revealed diffuse nodules with tree-in-bud signs and new consolidation within the irradiated area, leading to a diagnosis of combined DPB and radiation pneumonitis. The patient’s symptoms and lung imaging findings significantly improved after the initiation of low-dose oral azithromycin for DPB and low-dose glucocorticoid therapy for radiation pneumonitis.ConclusionsClinicians should consider DPB in patients with thymoma and cellular immunodeficiency. Both thymectomy and radiation therapy can contribute to the development of DPB. Early treatment with macrolides can improve patient prognosis.
Addressing the gap in preterm resuscitation practices in high-income and low-middle income countries: a multicenter survey of the Asian neonatal network collaboration
Authors: Rohsiswatmo Rinawati , Dewi Rizalya , Sutantio Jennie , Amin Zubair , Youn Young-Ah , Kim Sae Yun , Cho Su Jin , Chang Yun Sil , Kusuda Satoshi , Miyake Fuyu , Isayama Tetsuya 
Published: January 2025

BackgroundOptimum neonatal resuscitation practices are vital for improving neonatal survival and neurodevelopment outcomes, particularly in extremely preterm infants. However, such practices may vary between high-income countries (HICs) and low-middle-income countries (LMICs). This study aimed to evaluate the resuscitation practices of high-risk infants in a large multi-country sample of healthcare facilities among HICs and LMICs in Asia under the AsianNeo Network.MethodsIn 2021, a customized 6-item online survey on resuscitation practices of infants born at &lt;29 weeks gestation (or birth weight &lt;1,200 g) was sent by the representative of each country's neonatal network to all the Neonatal Intensive Care Units (NICUs) participating in AsianNeo network. At the time of the survey, there were 446 participating hospitals in eight countries: four high-income countries (Japan, Singapore, South Korea, and Taiwan) and four low-middle-income countries (Malaysia, Indonesia, Philippines, and Thailand).ResultsThe study included 446 hospitals, with a response rate of 72.6% (ranging from 62.7% to 100%), with 179 (55.2%) in HICs and 145 (44.7%) in LMICs. Routine attendance of experienced NICU physicians during resuscitations is reported to be higher in HICs than LMICs, both during daytime (79% vs. 40%) and nighttime (62% vs. 23%). The NRP guidelines in each country were varied, with 4 out of 8 countries using indigenously developed guidelines. Equipment availability during resuscitation was also variable; saturation monitors, radiant warmers, and plastic wraps were available in almost all hospitals, whereas oxygen and air blenders, heated humidified gas, and end-tidal CO2 detectors were more available in HICs. The most common device for Positive Pressure Ventilation (PPV) was the T-piece resuscitator (52.3%).ConclusionThe neonatal resuscitation practices for extremely preterm infants, encompassing staff, equipment, and guidelines, exhibited variance between HICs and LMICs in the AsianNeo region. Further enhancements are imperative to narrow this gap and optimize neonatal outcomes.
Mechanism of salvianolic phenolic acids and hawthorn triterpenic acids combination in intervening atherosclerosis: network pharmacology, molecular docking, and experimental validation
Authors: Zhai Qu , Shang Shixi , Zhang Zihan , Sun Lihua , Huang Ying , Feng Shuyi , Wu Qian , Cui Haifeng , Shi Xiaolu 
Published: January 2025

BackgroundThis study employs network pharmacology and molecular docking methods in conjunction with animal experimentation to elucidate the underlying mechanism by which the combination of salvianolic phenolic acids and hawthorn triterpenic acids (SHC) exerts its therapeutic effect on carotid atherosclerosis (AS) in ApoE−/− mice.MethodsA network pharmacology research approach was used to predict potential core targets for SHC intervention in atherosclerosis. The predictions were subsequently validated through the implementation of animal in vivo experiments. ApoE−/− mice were randomly assigned to three experimental groups, namely, a model group, an atorvastatin group, and an SHC group. After the administration period, the plaque area in the carotid artery and aortic arch, blood lipid levels, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO) content were measured. Additionally, the expression of PI3K, Akt, NF-κB, JNK1, ERK1/2, and p38-MAPK in the aortic arteries was analyzed. Based on the protein expression results, molecular docking was used to predict the binding activity between the core compounds and core targets.ResultsA total of 23 core compounds were identified in SHC, and 55 core targets of SHC were screened as potential targets for intervention in AS. The results of the enrichment analysis indicated that the principal mechanisms through which SHC exerts its effects in AS are associated with lipid metabolism and the PI3K-Akt and MAPK pathways. The results from animal experiments demonstrated that atorvastatin and SHC markedly reduced the area of carotid plaque and downregulated the levels of TC and LDL-C in ApoE−/− mice. The administration of SHC was associated with an increase in SOD activity and a reduction in NO levels in the livers of mice. Furthermore, SHC was observed to downregulate the expression of NF-κB and p38-MAPK in the carotid region. The results of molecular docking demonstrated that the core compounds of SHC, including salvianolic acid A, B, and C, maslinic acid, ursolic acid, and oleic acid, were capable of stably binding to the core targets NF-κB and MAPK14.ConclusionIt is hypothesized that SHC may reduce lipid deposition and plaque formation in AS by regulating blood lipids, a process that may be closely linked to the inhibition of inflammatory regulator expression, including NF-κB and p38-MAPK.
Roles of retinoic acid-related orphan receptor α in high glucose-induced cardiac fibroblasts proliferation
Authors: San Wenqing , Zhou Qianyou , Shen Danning , Cao Danyi , Chen Yun , Meng Guoliang 
Published: January 2025

Diabetic cardiomyopathy, characterized by myocardial fibrosis, is a common complication of diabetes. Retinoic acid-related orphan receptor α (RORα) participates in various pathological and physiological cardiovascular processes. The current research aims to elucidate the roles and mechanisms of RORα in high glucose induced cardiac fibroblasts proliferation. Primary neonatal cardiac fibroblasts were isolated from Sprague-Dawley rats, and pre-administrated with RORα antagonist SR3335 (20 µM) or RORα agonist SR1078 (10 µM) followed by the stimulation with normal glucose (5.5 mM) or high glucose (33.3 mM) respectively. Lactate Dehydrogenase (LDH) release into culture medium, cellular adenosine-triphosphate (ATP), and cell number were detected. Expressions of Collagen I, Collagen III, proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) were evaluated. The extent of oxidative stress was also assessed. Our study found that high glucose elevated LDH release, reduced cellular ATP production, increased cells numbers, elevated expression of Collagen I, Collagen III, PCNA, α-SMA, RIPK1 and RIPK3, decreased mitochondrial membrane potential, strengthened intensity of dihydroethidium (DHE) and MitoSOX fluorescence. Above effects were all further exacerbated by SR3335 but significantly reversed by SR1078. In conclusion, RORα antagonist SR3335 promoted cell injury and proliferation, enhanced collagen synthesis, facilitated oxidative stress and necroptosis in cardiac fibroblasts with high glucose stimulation, whereas RORα agonist SR1078 showed opposing effects. Our study proposed RORα as a novel target against high glucose-induced cardiac fibroblasts proliferation, which is beneficial to clarify ideal therapeutic implication for diabetic cardiomyopathy.
Comparative evaluation of intravenous versus intranasal dexmedetomidine on emergence delirium and hemodynamics in pediatric patients undergoing adenotonsillectomy: a randomized controlled trial
Authors: Dai Chenxu , Zhao Xuemei , Li Aoxue , Zhang Xuedong , Wang Penglei , Zhang Ye , Wu Yun 
Published: January 2025

BackgroundDexmedetomidine effectively prevents emergence delirium in children. However, intravenous dexmedetomidine is frequently associated with hemodynamic instability and delayed recovery. Intranasal dexmedetomidine has been proposed as a method of reducing these side effects. This study aimed to evaluate the effects of intranasal versus intravenous dexmedetomidine on emergence recovery and hemodynamics in children undergoing adenotonsillectomy.MethodsA total of 139 children, aged 3–10 years, who were scheduled for elective adenotonsillectomy were randomly assigned to receive intravenous dexmedetomidine (IV DEX group) or intranasal dexmedetomidine (IN DEX group), or saline (control group) after anesthesia induction. The primary outcome was the highest score on the pediatric anesthesia emergence delirium (PAED) score during the first 30 min after awakening. Secondary outcomes included the perioperative blood pressure and heart rate, time to awakening, postoperative pain score, and length of post-anesthesia care unit (PACU) stay.ResultsThe highest PAED and pain scores were significantly lower in the IV and IN DEX groups than those in the control group during the first 30 min after awakening. However, no significant differences were observed between the IV and IN DEX groups. Notably, patients in the IN DEX group exhibited a significantly lower PAED score at 2 h and lower pain scores at 2, 4, and 6 h postoperatively than those in the IV DEX group. Patients in the IV DEX group exhibited a significantly longer awakening time and length of PACU stay than those in the IN DEX and control groups. In the IV DEX group, the heart rate was significantly lower perioperatively than at baseline, while this effect was not observed in the IN DEX group.ConclusionBoth intravenous and intranasal administration of dexmedetomidine after induction of anesthesia effectively improved emergence delirium and pain intensity in children undergoing adenotonsillectomy. Intranasal administration of dexmedetomidine provided more stable hemodynamics and more prolonged analgesia and sedation than intravenous infusion of dexmedetomidine.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=180658.
Distinct lipidomic profiles but similar improvements in aerobic capacity following sprint interval training versus moderate-intensity continuous training in male adolescents
Authors: Su Wantang , Liu Jianming , Wang Aozhe , Zhang Haifeng , Sun Yaqi , Yan Zhiyi , Svensson Michael , Yu Ji-Guo , Zhao Li 
Published: January 2025

BackgroundExercise-induced metabolic changes, especially lipidomic changes are generally associated with improvements in cardiovascular health. Despite numerous previous studies, the differences in lipidomic profile response to different types of exercise training remain unclear. This study aimed to investigate how two different exercise intensities affect aerobic capacity and serum lipidomic profiles in healthy adolescents.MethodsTwenty-four healthy untrained male adolescents (13.08 ± 0.88 years old) were recruited and randomly assigned to moderate-intensity continuous training (MICT) group or sprint interval training (SIT) group to complete a specific training on a cycle ergometer for 6 weeks. Peak oxygen uptake (VO2peak) and body composition were measured, and blood samples were collected for serum lipoproteins and lipidomic analysis. Anthropometric, VO2peak, and serum biochemical data were analyzed using two-way repeated analysis of variance, while targeted lipidomic analysis was performed by principal component analysis and paired-sample t-test.ResultsVO2peak significantly improved from 39.05 ± 8.17 to 47.52 ± 8.51 [F (1, 44) = 14.75, p &lt; 0.05] for MICT and from 40.13 ± 6.37 to 48.42 ± 7.01 [F (1, 44) = 14.75, p &lt; 0.05] for SIT. A total of 28 lipids in MICT and 5 lipids in SIT showed significant changes out of 276 identified lipids (FC &gt; 1.5 or &lt;1/1.5, FDR &lt;0.05). In MICT, 21 lipids, including sphingolipid (SP) and phospholipid (PL), decreased, while 7 lipids increased. In SIT, all 5 lipids, which were free fatty acid (FFA), decreased.ConclusionAlthough both MICT and SIT induced similar and significant improvements in VO2peak, serum lipid adaptations to the training differed. The primary changes in serum lipidomic intermediates for both types of training were reductions; however, SIT affected FFA, while MICT predominantly influenced SPs and PLs.
Closed-loop systems for plants expressing animal proteins: a modernized framework to safeguard the future of agricultural innovation
Authors: Bresnahan Kristin A. , Ferber Justin M. , Carrato J. Thomas , Stoddard Thomas J. , Palad Patrick V. , Richani Magi 
Published: January 2025

Escalating population growth and climate change pressures on crop production necessitate agricultural innovation to ensure food security and sustainability. Plant molecular farming (PMF), which uses genetically modified (GM) plants to produce high-value proteins for food products, offers a promising solution. PMF products, particularly those that express an animal protein in seed and grain crops, have the potential to substantially benefit U.S. and global agriculture, food systems, economies, and the environment. Farmers can diversify and generate increased revenue streams, while consumers gain access to affordable proteins beyond those currently available. However, the development and commercialization of PMF products, especially those expressing allergenic animal proteins, require careful consideration of existing stewardship guidelines and best practices. Current GM plant stewardship practices must be thoroughly assessed to identify and address any gaps, ensuring that PMF products maintain identity preservation and containment throughout their lifecycle. Implementing a fit-for-purpose closed-loop system (CLS) is crucial for effectively identifying, managing, and mitigating the potential risks and liabilities associated with PMF product development, production, and processing. A CLS framework for PMF products expressing animal proteins should integrate existing best practices from Excellence Through Stewardship and applicable third-party guidelines, including by way of example ISO standards, Good Manufacturing Practices, Hazard Analysis and Risk-Based Preventive Controls, Hazard Analysis and Critical Control Points, and Safe Quality Food, as well as newly designed controls to address potential PMF-specific risks. This comprehensive approach maximizes containment, identity preservation, regulatory compliance, traceability, incident response capabilities, and continuous improvement across the product lifecycle. While customization is required based on each PMF product developer’s specific product and operations, this paper examines industry best practices and describes CLS components that a PMF developer should consider in designing a robust, bespoke CLS to maintain identity preservation and product containment. Such a system will optimize for product quality and integrity while preventing commingling with commodity supplies and any associated market disruption while also addressing food safety. By implementing these rigorous systems, the PMF industry can realize its potential to contribute significantly to sustainable agriculture and food security.
Enhancing work life through social cognition: the effect of SCIT in bipolar disorder
Authors: Anaforoglu Bikmaz Zeynep , Mackali Zeynep , Cakir Sibel 
Published: January 2025

ObjectivesThis study aimed to investigate the effectiveness of social cognition and interaction therapy (SCIT) in improving occupational functioning in individuals diagnosed with bipolar disorder I (BD-I). The effects of SCIT intervention with standard treatment methods were investigated on social cognition and functioning effects, which are often negatively affected in patients with BD-I.MethodsThe research involved 28 participants, allocated into two groups: An experimental group (n = 12) receiving SCIT for 8 weeks alongside standard treatments (pharmacotherapy and psychiatric interviews), and a control group (n = 16) undergoing standard treatment without additional interventions. Outcome measures were assessed using a suite of tools, including the Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Eyes Test (ET), Metacognition Scale (MCI), Internalized Stigma of Mental Illnesses (ISMI), and Functioning Assessment Short Test (FAST). Given the small sample size, non-parametric tests were employed for data analysis. Analyses were conducted using the Mann–Whitney U test and Wilcoxon test for comparisons between the experimental and control groups and within groups. Also, the effects of the intervention on social cognition, occupational functioning and resistance to stigmatization were dealt.ResultsThe findings revealed that participants in the experimental group showed significant improvements in social cognition and occupational functioning after SCIT compared to the control group. However, the levels of stigmatization experienced by individuals as a result of ISMI measurements were significantly lower in the SCIT group compared to the control group.ConclusionThe study concludes that SCIT can be an effective intervention for enhancing certain psychosocial and cognitive functions in individuals with BD-I, thereby improving their occupational functioning. Nevertheless, the persistent levels of stigma indicate the need for additional strategies to address the broader challenges faced by individuals with BD-I in terms of societal perception and self-stigmatization.