bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the in vitro metabolic stability of CEP-37440, a selective FAK/ALK inhibitor, in HLMs using fast UPLC–MS/MS method: in silico metabolic lability and DEREK alerts screening
Authors: Attwa Mohamed W. , AlRabiah Haitham , Abdelhameed Ali S. , Kadi Adnan A. 
Published: September 2024

IntroductionCEP-37440 was synthesized and supplied by the research and development division of Teva Branded Pharmaceutical Products (West Chester, PA, United States). CEP-37440 represents a newly developed compound that exhibits selectivity inhibition of Focal Adhesion Kinase and Anaplastic Lymphoma Kinase FAK/ALK receptors, demonstrating novel characteristics as an orally active inhibitor. The simultaneous inhibition of ALK and FAK can effectively address resistance and enhance the therapeutic efficacy against tumors through a synergistic mechanism.MethodsThe objective of this research was to create an LC-MS/MS method that is precise, efficient, environmentally friendly, and possesses a high level of sensitivity for the quantification of CEP-37440 in human liver microsomes (HLMs). The aforementioned approach was subsequently employed to evaluate the metabolic stability of CEP-37440 in HLMs in an in vitro setting. The validation procedures for the LC-MS/MS analytical method in the HLMs were performed following the bio-analytical method validation guidelines set out by the US-FDA. The AGREE program was utilized to assess the ecological impacts of the current LC-MS/MS methodology.Results and DiscussionThe calibration curve linearity was seen in the range of 1–3000 ng/mL. The inter-day accuracy (% RE) exhibited a range of −2.33% to 3.22%, whilst the intra-day accuracy demonstrated a range of −4.33% to 1.39%. The inter-day precision (% RSD) exhibited a range of 0.38% to 3.60%, whilst the intra-day precision demonstrated a range of 0.16% to 6.28%. The determination of the in vitro half-life (t1/2) and moderate intrinsic clearance (Clint) of CEP-37440 yielded values of 23.24 min and 34.74 mL/min/kg, respectively. The current manuscript is considered the first analytical study for CEP-37440 quantification with the application to metabolic stability assessment. These results suggest that CEP-37440 can be categorized as a pharmaceutical agent with a moderate extraction ratio. Consequently, it is postulated that the administration of CEP-37440 to patients may not lead to the accrual of dosages within the human organs. According to in silico P450 metabolic and DEREK software, minor structural alterations to the ethanolamine moiety or substitution of the group in drug design have the potential to enhance the metabolic stability and safety profile of novel derivatives in comparison to CEP-37440.
Common mental disorders and risk of female infertility: a two-sample Mendelian randomization study
Authors: Mao Di , Lin Mingmei , Li Rong 
Published: September 2024

IntroductionFemale infertility is a global issue that impacts on public health seriously and many mental disorders are observed in infertility groups.MethodsTo investigate the casual relationship between those, genome-wide association studies summary data of anxiety disorder (n=9,897), broad depression (n=322,580), major depressive disorder (n=480,359 and n=500,199), bipolar disorder (n=51,710), insomnia (n= 462,341), and female infertility (n=126,342) were extracted from the existing datasets and was analyzed through the two-sample mendelian randomization study. The following heterogeneity and sensitivity test were applied to ensure the robustness of results.ResultsBased on inverse variance weighted results, major depressive disorder was associated with female infertility (P = 0.0001, odds ratio 1.396, 95 % confidence interval 1.175–1.658). No causal relationship was identified between the other four mental disorders and infertility. was found. Additionally, reverse mendelian randomization did not indicate a causal relationship among these disorders.DiscussionThe early identification and management of anxiety symptoms in women of reproductive age, in conjunction with the effective treatment of major depressive disorder, may be crucial for preserving female fertility.
Peripheral NK cell count predicts response and prognosis in breast cancer patients underwent neoadjuvant chemotherapy
Authors: Zhang Chao , Wu Fengjia , Lu Xiuqing , Wang Sifen , Wu Minqing , Chen Nian , Fan Shanji , Wei Weidong 
Published: September 2024

PurposeThe count of lymphocyte subsets in blood can reflect the immune status of the body which is closely related to the tumor immune microenvironment and the efficacy of NAT. This study aims to explore the relationship between peripheral blood lymphocyte subsets and the efficacy and prognosis of NAT in breast cancer.MethodsWe retrospectively analyzed clinicopathological information and peripheral blood lymphocyte subpopulation counts of patients receiving NAT from January 2015 to November 2021 at Sun Yat-sen University Cancer Center. Kaplan-Meier curves were used to estimate the survival probability. The independent predictors of NAT response and survival prognosis were respectively analyzed by multivariate logistic regression and Cox regression, and nomograms were constructed accordingly. The prediction efficiency of three nomograms was validated separately in the training cohort and the testing cohort.Results230 patients were included in the study, consisting of 161 in the training cohort and 69 in the testing cohort. After a median follow-up of 1238 days, patients with higher NK cell value showed higher pCR rates and higher OS and RFS after NAT (all P &lt; 0.001). Multivariate analyses suggested NK cell count was an independent predictor of NAT response, OS and RFS. We then built nomograms accordingly and validated the prediction performance in the testing cohort (C index for NAT response: 0.786; for OS: 0.877, for RFS: 0.794).ConclusionPeripheral blood NK cell count is a potential predictive marker for BC patients receiving NAT. Nomograms based on it might help predict NAT response and prognosis in BC.
Differential microbiome features in lake–river systems of Taihu basin in response to water flow disturbance
Authors: Xiao Peng , Wu Yao , Zuo Jun , Grossart Hans-Peter , Sun Rui , Li Guoyou , Jiang Haoran , Cheng Yao , Wang Zeshuang , Geng Ruozhen , Zhang He , Ma Zengling , Yan Ailing , Li Renhui 
Published: September 2024

IntroductionIn riverine ecosystems, dynamic interplay between hydrological conditions, such as flow rate, water level, and rainfall, significantly shape the structure and function of bacterial and microeukaryotic communities, with consequences for biogeochemical cycles and ecological stability. Lake Taihu, one of China’s largest freshwater lakes, frequently experiences cyanobacterial blooms primarily driven by nutrient over-enrichment and hydrological changes, posing severe threats to water quality, aquatic life, and surrounding human populations. This study explored how varying water flow disturbances influence microbial diversity and community assembly within the interconnected river–lake systems of the East and South of Lake Taihu (ET&amp;ST). The Taipu River in the ET region accounts for nearly one-third of Lake Taihu’s outflow, while the ST region includes the Changdougang and Xiaomeigang rivers, which act as inflow rivers. These two rivers not only channel water into Lake Taihu but can also cause the backflow of lake water into the rivers, creating distinct river–lake systems subjected to different intensities of water flow disturbances.MethodsUtilizing high-throughput sequencing, we selected 22 sampling sites in the ET and ST interconnected river-lake systems and conducted seasonally assessments of bacterial and microeukaryotic community dynamics. We then compared differences in microbial diversity, community assembly, and co-occurrence networks between the two regions under varying hydrological regimes.Results and discussionThis study demonstrated that water flow intensity and temperature disturbances significantly influenced diversity, community structure, community assembly, ecological niches, and coexistence networks of bacterial and eukaryotic microbes. In the ET region, where water flow disturbances were stronger, microbial richness significantly increased, and phylogenetic relationships were closer, yet variations in community structure were greater than in the ST region, which experienced milder water flow disturbances. Additionally, migration and dispersal rates of microbes in the ET region, along with the impact of dispersal limitations, were significantly higher than in the ST region. High flow disturbances notably reduced microbial niche width and overlap, decreasing the complexity and stability of microbial coexistence networks. Moreover, path analysis indicated that microeukaryotic communities exhibited a stronger response to water flow disturbances than bacterial communities. Our findings underscore the critical need to consider the effects of hydrological disturbance on microbial diversity, community assembly, and coexistence networks when developing strategies to manage and protect river–lake ecosystems, particularly in efforts to control cyanobacterial blooms in Lake Taihu.
Albumin adjuvant therapy for acute ischemic stroke with large vessel occlusion (AMASS-LVO): rationale, design, and protocol for a phase 1, open-label, clinical trial
Authors: Pan Sihu , Du Kangjie , Liu Shuling , Wang Sifei , Luo Leilei , Xu Yongbo , Cao Chen , Chen Jian , Ji Xunming , Wei Ming 
Published: September 2024

BackgroundAcute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS.MethodsThis study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0–2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles.ConclusionThis pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions.Clinical trial registrationClinicalTrials.gov, NCT05953623.
Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy
Authors: Ren Yu , Zhu Yanwu , Yan Qiaoyan , Jin Hui , Luo Hua 
Published: September 2024

ObjectivesCoronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients’ post-CABG.MethodsThis retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups.ResultsOver the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin.ConclusionIndobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.
The effect of childhood trauma on moral cognition in patients with schizophrenia
Authors: Peng Xing , Ding Yu-shen , Ren Bo , Zhao Xi-xi , Wang Fei-fei , Zhao Jie , Zhang Yuan-yuan , Zhang Xiu-jun , Zhou Fu-chun , Wang Chuan-yue 
Published: September 2024

ObjectiveThe aim of this study was to investigate whether a potential moral cognitive impairment (failure in understanding moral rules) exists in patients with schizophrenia (SCZ) and to explore the effect of childhood trauma (CT) on moral cognition in a group of patients with SCZ.MethodsA total of 99 patients with SCZ and 102 healthy controls (HCs) were included in this study. The Childhood Trauma Questionnaire-Short Form (CTQ) was administered to assess childhood trauma experiences in both groups, while the Moral Identity Measure (MIM) and the Moral Foundations Questionnaire (MFQ) were applied for a comparative evaluation of moral cognition across the two groups. The Positive and Negative Syndrome Scale (PANSS) was administered to assess the psychopathology.ResultsPatients with schizophrenia had significantly greater CTQ scores than HCs (42.77 ± 13.50 vs. 29.11 ± 4.25, t=9.697, p&lt;0.001). The prevalence of childhood trauma (χ2 = 58.452, p&lt;0.001) and history of aggressive behaviors (χ2 = 23.565, p=0.001) among patients with SCZ were greater than that among HCs. In addition, the scores of moral cognition (MIM: 61.82 ± 15.12 vs. 70.88 ± 8.87, p=0.001; MFQ: 87.24 ± 22.30 vs. 112.62 ± 23.42, p=0.045) in the SCZ group was lower than that in the HC group after controlling for the influence of CT covariates. The MFQ score was negatively correlated with the CTQ score, the emotional abuse (EA) score, the physical abuse (PA) score and the physical neglect (PN) score in SCZ patients. Among HCs, the MFQ score was positively correlated with the CTQ score, as well as with the dimensions of physical abuse (PA) and emotional Neglect (EN). Multiple linear regression analyses revealed that impaired moral cognition performance was significantly predicted by the CTQ score (beta=-0.235, p=0.034, 95% CI -0.743 to -0.031) in patients with SCZ but was significantly predicted by years of education (beta=-0.392, p&lt;0.001, 95% CI -4.783 to -1.876), alcohol use (beta=0.210, p=0.023, 95% CI 2.191 to 29.399) and the CTQ score (beta=0.184, p=0.046, 95% CI 0.019 to 1.928) in HCs. CTQ moderated the effect of SCZ on MFQ (B = 0.516); Simple tests revealed that the group effect on the MFQ was B=12.306 at the lower level(-1SD) and B = 54.089 at the higher level(+1SD) of the CTQ scores.ConclusionsSCZ patients exhibit impaired moral cognition. The contribution of CT to the presence of moral cognitive impairments seems to be independent of psychopathology.
Chemical Composition and Antioxidant Activity of Six Allium Extracts Using Protein-Based Biomimetic Methods
Authors: Barbu Ioana Andreea , Toma Vlad Alexandru , Moț Augustin Cătălin , Vlase Ana-Maria , Butiuc-Keul Anca , Pârvu Marcel 
Published: September 2024

Medicinal plants are a valuable reservoir of novel pharmacologically active compounds. ROS and free radicals are primary contributors to oxidative stress, a condition associated with the onset of degenerative diseases such as cancer, coronary heart disease, and vascular disease. In this study, we used different spectrophotometry methods to demonstrate the antioxidant properties of 6 Allium extracts: Allium fistulosum; Allium ursinum; Allium cepa: Arieș red cultivar of A. cepa, and white variety of A. cepa; Allium sativum; and Allium senescens subsp. montanum. HPLC–MS determined the chemical composition of the extracts. Among the tested extracts, the Arieș red cultivar of A. cepa stands out as having the best antioxidant activity, probably due to the high content of polyphenols and alliin (12.67 µg/mL and 3565 ng/mL, respectively). The results obtained in this study show that Allium extracts have antioxidant activity, but also free radical scavenging capabilities. Also, their interactions with cytochrome c and hemoglobin can be the basis of future studies to create treatments for oxidative stress-related diseases.
REAL-TIME NETWORK TRAFFIC PREDICTION USING HYBRID ARIMA-GARCH MODELS
Authors: Гребенщикова А.А. 
Published: September 2024

Модели с обобщенной авторегрессионной условной гетероскедастичностью GARCH часто используются при прогнозировании временных рядов для управления волатильностью данных. В данном исследовании изучается эффективность гибридизации моделей авторегрессии и проинтегрированного скользящего среднего (ARIMA) и GARCH с преобразованием Бокса-Кокса для анализа и прогнозирования сетевого трафика реального времени. Преобразование Бокса-Кокса используется для нормализации данных, стабилизации дисперсии и уменьшения гетероскедастичности. Порядки p и q в моделях ARIMA были определены и оценены в соответствии с методологией Бокса-Дженкинса. Диагностика моделей проводилась с применением Q-статистики Льюнга-Бокса, теста на гетероскедастичность и анализа нормальности распределения остатков моделей ARIMA(p,d,q) и ARIMA(p,d,q)-GARCH(s,r).
Generalized autoregressive conditional heteroscedasticity (GARCH) models are often used in time series forecasting to control for data volatility. This study investigates the performance of hybridization of autoregressive integrated moving average (ARIMA) and GARCH models with Box-Cox transform for real-time network traffic analysis and forecasting. The Box-Cox transformation is used to normalize data, stabilize variance, and reduce heteroscedasticity. The orders of p and q in the ARIMA models were determined and estimated according to the Box Jenkins methodology. Model diagnostics were performed using the Ljung-Box Q-statistic, heteroscedasticity test, and analysis of the normality of the distribution of residuals of the ARIMA(p,d,q) and ARIMA(p,d,q)-GARCH(s,r) models.
INTELLIGENT CORE FOR 6G INTEGRATED NETWORK BASED ON SDN TO SUPPORT TELEPRESENCE APPLICATIONS
Authors: Кузнецов К.А. 
Published: September 2024

С появлением услуг телеприсутствия возник ряд вопросов и ограничений, связанных с передачей всех человеческих ощущений на расстоянии. В статье предлагается метод оптимизации количества контроллеров в программно-определяемых сетях (SDN). В ходе эксперимента удалось сократить количество контроллеров на 46% и в то же время повысить эффективность использования каждого из них на 53%.
With the advent of telepresence services, a number of issues and constraints have arisen related to the transmission of all human sensations at a distance. The paper proposes a method to optimize the number of controllers in SDN networks. The experiment succeeded in reducing the number of controllers by 46%, at the same time increasing the utilization efficiency of each controller by 53%.
COMPREHENSIVE CRITERION FOR THE EFFECTIVENESS OF A SATELLITE COMMUNICATION SYSTEM
Authors: Нестеров Е.А. , Гусев В.М. , Кургузов Р.Ю. , Цым А.Ю. 
Published: September 2024

Показана целесообразность введения комплексного критерия эффективности на этапе разработки инновационной системы высокого уровня сложности, характеризующейся значительным количеством составных частей и трудно совместимых друг с другом требований. Без ограничения общности введение такого критерия, построенного на основе классической теории квалиметрии, показано на примере создания национальной гибридной наземно-космической сети связи. Наличие комплексного критерия эффективности позволяет независимым группам разработчиков производить оптимизацию параметров составных частей национальной гибридной сети связи при обеспечении ее эффективности и конкурентоспособности в целом.
The expediency of introducing a comprehensive efficiency criterion at the stage of developing an innovative system of a high level of complexity, characterized by a significant number of components and requirements that are difficult to reconcile with each other, is shown. Without limiting generality, the introduction of such a criterion, based on the classical theory of qualimetry, is shown by the example of the creation of a national hybrid ground-space communication network. The presence of a comprehensive efficiency criterion allows independent development groups to optimize the parameters of the components of the national hybrid communications network while ensuring its efficiency and competitiveness as a whole.