bluuebunny/crossref_metadata_2025_split huggingface dataset:
From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy
Authors: Pinto E. , Lione L. , Compagnone M. , Paccagnella M. , Salvatori E. , Greco M. , Frezza V. , Marra E. , Aurisicchio L. , Roscilli G. , Conforti A. 
Published: January 2025

AbstractIn the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to the approval of six therapeutic products for haematological malignancies. Recently, the therapeutic potential of this therapy has also been demonstrated in non-tumoral diseases. Currently, the manufacturing process to produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive. It involves multiple steps, including the collection of T cells from patients or healthy donors, in vitro engineering and expansion, and finally reinfusion into patients. Therefore, despite the impressive clinical outcomes, ex vivo manufacturing process makes CAR-T cells out of reach for many cancer patients. Direct in vivo engineering of T cells could be a more rapid solution able to circumvent both the complexity and the costs associated with ex vivo manufactured CAR-T cells. This novel approach allows to completely eliminate ex vivo cell manipulation and expansion while producing therapeutic cell populations directly in vivo. To date, several studies have demonstrated the feasibility of in vivo T cell reprogramming, by employing injectable viral- or nanocarrier-based delivery platforms in tumour animal models. Additionally, in vivo production of CAR-T cells might reduce the incidence, or at least the severity, of systemic toxicities frequently occurring with ex vivo produced CAR-T cells, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this review, we highlight the challenges associated with the current ex vivo manufacturing protocols and review the latest progresses in the emerging field of in vivo CAR-T therapy, by comparing the various platforms so far investigated. Moreover, we offer an overview of the advantages deriving from in vivo reprogramming of other immune cell types, such as Natural Killer and macrophages, with CAR constructs.
Increasing and maintaining rates of standardized depression screening in youth with childhood-onset systemic lupus erythematosus in a pediatric rheumatology clinic
Authors: Datyner Emily , Dingle Jodi , Newsome Victoria , Buckley Lisa H. , Belsky Natasha , Park Seungweon , Mitchell Manda , Fine Brooke , Patterson Barron , Graham T. Brent , Davis Alaina 
Published: January 2025

Abstract
Background
Depression adversely affects health outcomes in patients with childhood-onset systemic lupus erythematous (cSLE). By identifying patients with depressive symptoms, we can intervene early with referrals to mental health resources and improve outcomes. The aim of our quality improvement project was to increase and maintain rates of standardized depression screening for youth with cSLE seen within our pediatric rheumatology clinic.

Methods
Patients with cSLE 12 years of age or older seen for routine follow-up at our pediatric rheumatology clinic from September 16, 2019, through December 30, 2022, were offered the Patient Health Questionnaire-9 modified for adolescents (PHQ-A) to screen for depressive symptoms. A multidisciplinary team developed a key driver diagram to plan potential interventions to improve rates of screening. Plan‒Do‒Study‒Act (PDSA) cycles were used to prepare, implement, and evaluate interventions. Notable interventions focused on accurately identifying eligible patients, facilitating bidirectional communication between staff, and integrating and automating screening within the electronic health record (EHR). Statistical process control (SPC) methods were used for data analysis.

Results
The percentage of eligible patient encounters where depression screening was completed increased from 0 to 81% and was maintained for more than 6 months. This represents special cause variation, as evidenced by data shifts on our statistical process control chart. Among the 592 patients who completed depression screens, 114 (17%) were positive for moderate to severe symptoms, and 59 (9%) were positive for suicidal ideation (SI).

Conclusions
A high rate of standardized depression screening for youth with cSLE was achieved and maintained via integration and automation within our EHR. Establishing a highly reliable screening system is a critical first step in improving mental health care for this vulnerable population of youth.
Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke
Authors: Yang Xi-chen , Jin Ya-ju , Ning Rong , Mao Qiu-yue , Zhang Peng-yue , Zhou Li , Zhang Cheng-cai , Peng Yi-chen , Chen Na 
Published: January 2025

Abstract
Objective
Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis has been shown to play a key role in the injury process. In the present study, we wanted to explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation.

Methods
The ischemic stroke model was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in adult rats. These rats have been randomly divided into the EA + MCAO/R group, the MCAO/R group, the EA + MCAO/R + Brusatol group (the inhibitor of Nrf2), and the EA + MCAO/R + DMSO group, and the Sham group. The EA + MCAO/R group, EA + MCAO/R + Brusatol group, and the EA + MCAO/R + DMSO group received EA intervention 24 h after modeling for 7 consecutive days. The behavioral function was evaluated by Neurologic severity score (NSS), Garcia score, Foot-fault Test, and Rotarod Test. The infarct volume was detected by TTC staining, and the neuronal damage was observed by Nissl staining. The levels of Fe2+, reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by ELISA. The immunofluorescence and Western blotting were used to detect the expression of Total Nrf2, p-Nrf2, Nuclear Nrf2, and Cytoplasmic Nrf2, and the essential ferroptosis proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1). The mitochondria were observed by transmission electron microscopy (TEM).

Results
Electroacupuncture improved neurological deficits in rats model of MCAO/R, decreased the brain infarct volume, alleviated neuronal damage, inhibited the Fe2+, ROS, and MDA accumulation, increased SOD levels, increased the expression of GPX4, SLC7A11 and FTH1, and rescued injured mitochondria. Especially, we found that the electroacupuncture up-regulated the expression of Nrf2, and promoted phosphorylation of Nrf2 and nuclear translocation, However, Nrf2 inhibitor Brusatol reversed the neuroprotective effect of electroacupuncture.

Conclusion
Electroacupuncture can alleviate cerebral I/R injury-induced ferroptosis by promoting Nrf2 nuclear translocation. It is expected that these data will provide novel insights into the mechanisms of electroacupuncture protecting against cerebral I/R injury and potential targets underlying ferroptosis in the stroke.

Graphical Abstract
Jianwei Xiaoshi oral liquid attenuates high-calorie diet-induced dyspepsia in immature rats via regulating the pancreatic secretion pathway and maintaining the homeostasis of intestinal microbiota
Authors: Zhang Yan , Wei Xiaolu , Jiang Shan , Gao Wenya , Wang Kun , Wang Hongjie , Wang Huijun , Si Nan , Zhou Yanyan , Luo Keke , Wang Mengxiao , Liu Yuyang , Chen Lihua , Ni Liqi , Zhao Haiyu 
Published: January 2025

Abstract
Background
Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.

Methods
To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC–Q–Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia.

Results
A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body.

Conclusion
JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders.

Graphical Abstract
Evaluating the effectiveness of Pisolithus tinctorius in enhancing the Eucalyptus’ resistance to salt stress
Authors: Zayed Mona S. , Ahmed Aya G. A. , Selim Shawky M. , Abd El-Fattah Dalia A. 
Published: January 2025

AbstractAfforestation projects on saline land, using Eucalyptus trees and ectomycorrhizal fungi, are crucial for restoring affected areas and promoting ecological and economic benefits, particularly in saline-affected areas. This study was conducted to isolate Pisolithus sp. and estimate its potential to improve the growth performance of Eucalyptus globulus seedlings under salt-stress conditions. Pisolithus sp. was isolated from mature sporocarps and identified through 18S rDNA. Pisolithus sp. was evaluated for its response to varying pH values, temperatures, and salinity levels. A pot experiment was conducted to assess the Pisolithus strain’s effectiveness in reducing soil salinity’s impact on the growth of Eucalyptus globulus seedlings in sandy soil. The identified Pisolithus tinctorius with an accession number of OM125275 revealed the highest mycelium dry weight of 0.09 g/100 ml medium at pH 5.8, 0.08 g/100 ml medium at 28 °C, and 0.12 g/100 ml medium at 4% NaCl. Eucalyptus globulus seedlings inoculated with Pisolithus tinctorius demonstrated significant improvement in most parameters compared to non-mycorrhizal (control) seedlings under salt stress. The seedlings inoculated with Pisolithus tinctorius and irrigated with 6 dS/m saline water revealed the highest shoot height (55.670 cm), root length (42.33 cm), shoot fresh weight (6.44 g/plant), root fresh weight (1.84 g/plant), shoot dry weight (2.37 g/plant), and root dry weight (0.810 g/plant) when compared to all treatments. Our findings suggest that selecting appropriate fungal strains is crucial for improving plant performance in saline conditions.
Graphical abstract
Antimicrobial activity of Monascus purpureus-derived red pigments against Salmonella typhimurium, Escherichia coli, and Enterococcus faecalis
Authors: Teiba Islam I. , Mamdouh Islam , Yousef Mokhtar I. , Hussein Ahmed , El-Bilawy Emad H. 
Published: January 2025

AbstractThe rise of antimicrobial-resistant microorganisms (AMR) poses a significant global challenge to human health and economic stability. In response, various scientific communities are seeking safe alternatives to antibiotics. This study comprehensively investigates the antibacterial effects of red dye derived from Monascus purpureus against three bacterial pathogens: Salmonella typhimurium ATCC14028, Escherichia coli ATCC8739, and Enterococcus faecalis ATCC25923. The dye was extracted from the Monascus purpureus ATCC16436 strain, using 1 mg of red dye in 1 ml of DMSO to achieve a concentration of 1000 µg/ml. The chemical profile of the red dye extract was analyzed using GC–MS analysis, confirming the presence of several bioactive antimicrobial compounds, including aspidospermidin-17-ol, 1-acetyl-16-methoxy, octanoic acid, and hexadecanoic acid methyl ester. The extract was tested against the bacterial strains at varying concentrations to determine the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). The results demonstrated significant antibacterial activity, with the highest MIC and MBC values of 6.25/12.5 µg/ml against S. typhimurium. The antibacterial activity of the red dye was compared to five conventional antibiotics using the disc diffusion method, revealing superior effectiveness, particularly against S. typhimurium, with an inhibition zone measuring 20 ± 0.22 mm. Scanning electron microscopy was employed to explore the mechanism of action of the red dye extract, highlighting its impact on bacterial plasma membrane permeability and its interference with cellular energy production. These findings suggest that the Monascus purpureus-derived red dye extract represents a promising natural alternative to conventional antibiotics, demonstrating potent antibacterial activity and potential as a novel therapeutic agent in combating antimicrobial resistance.
Melatonin improves endometrial receptivity and embryo implantation via MT2/PI3K/LIF signaling pathway in sows
Authors: Qin Xue , Yang Menghao , Yu Yang , Wang Xiaolin , Zheng Yi , Cai Rui , Pang Weijun 
Published: January 2025

Abstract
Background
Increased backfat thickness of sows in early gestation is negative to reproductive performance. Endometrial receptivity is an important determinant of reproductive success, but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits. The present study seeks to answer these questions through in vitro and in vivo investigations.

Results
Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows. In cells treated with melatonin, the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity. Furthermore, we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice. Notably, melatonin treatment caused a significant reduction in the deposition of endometrial collagen, an increase in the number of glands, and repair of the pinopode structure, ultimately improving endometrial receptivity, promoting embryo implantation, and increasing the number of litter size of mice.

Conclusions
Collectively, the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
Joint multifractality in cross-correlations between grains & oilseeds indices and external uncertainties
Authors: Shao Ying-Hui , Gao Xing-Lu , Yang Yan-Hong , Zhou Wei-Xing 
Published: January 2025

AbstractThis study investigates the relationships between agricultural spot markets and external uncertainties through multifractal detrending moving-average cross-correlation analysis (MF-X-DMA). The dataset contains the Grains & Oilseeds Index (GOI) and its five subindices for wheat, maize, soyabeans, rice, and barley. Moreover, we use three uncertainty proxies, namely, economic policy uncertainty (EPU), geopolitical risk (GPR), and Volatility Index (VIX). We observe multifractal cross-correlations between agricultural markets and uncertainties. Furthermore, statistical tests reveal that maize has intrinsic joint multifractality with all the uncertainty proxies, highly sensitive to external shocks. Additionally, intrinsic multifractality among GOI-GPR, wheat-GPR, and soyabeans-VIX is illustrated. However, other series have apparent multifractal cross-correlations with high probabilities. Moreover, our analysis suggests that among the three types of external uncertainties, GPR has the strongest association with grain prices, excluding maize and soyabeans.
Modeling the significance of unified theory of acceptance and use of technology in predicting the intention and usage of eCNY
Authors: Ma Yue , Al Mamun Abdullah , Masukujjaman Mohammad , Ja’afar Roslan 
Published: January 2025

AbstractThe introduction of the digital renminbi (eCNY) by the People's Bank of China serves as a means for the central bank to effectively comprehend macroeconomic dynamics and enhance payment infrastructure within the domestic market. Among the pioneering digital currencies, the eCNY is at the forefront of technological research and development, pilot implementation, and the establishment of a robust system. Thus, employing the unified theory of acceptance and use of technology, this study aims to explore the factors shaping the adoption of the eCNY and to determine the mediating effects of intention toward the eCNY and the moderating role of age and gender among various relationships. A cross-sectional survey methodology was deployed to collect data from pilot communities situated within the Yangtze River Delta, Pearl River Delta, and Beijing–Tianjin–Hebei regions. The empirical analysis comprised 809 valid online questionnaires, and the examination was conducted through structural equation modeling employing the partial least squares technique, ultimately subjecting the conceptual model to a comprehensive assessment. The results for intention to use the eCNY indicate that performance expectancy, effort expectancy, social influence, and perceived government policy have significant effects. Facilitating conditions and intentions toward the eCNY positively influenced its actual use. According to the findings of this study, age and sex did not moderate the effect of each hypothesis on the intention to use in the research model. This study breaks new ground by investigating the adoption of the eCNY, a novel form of currency, highlighting its multifaceted nature and providing empirical evidence for a comprehensive model encompassing psychological, social, and contextual factors. This study employs social surveys to identify obstacles in the process of promoting the widespread adoption of the eCNY and offers suggestions to the central bank and government to increase user enthusiasm and decrease user perceptions of risk, thereby promoting its widespread adoption.
Effect of right ventricular dysfunction on mortality in patients undergoing maintenance hemodialysis: a retrospective cohort study
Authors: Nobayashi Hiroki , Bamba Harui , Iida Tomomichi , Aoyagi Ryuji , Maruyama Yukio , Yokoo Takashi 
Published: January 2025

Abstract
Background
Cardiovascular disease (CVD) is a major complication in patients on maintenance hemodialysis (MHD). While the effect of left ventricular dysfunction on patients on MHD is well known, the association between right ventricular (RV) dysfunction and their prognosis remains poorly understood.

Methods
We conducted a retrospective cohort study of 149 patients on MHD (median age, 72 years; male, 67%) between 1 April 2022 and 31 March 2024. All subjects underwent transthoracic two-dimensional and Doppler echocardiographic examination. RV dysfunction was determined when the tricuspid annular plane systolic excursion (TAPSE) was under 16 mm. Kaplan–Meier survival analysis was used to compare survival between patients with and without RV dysfunction. Multivariate Cox regression analyses were used to estimate the effects of RV dysfunction on all-cause mortality, including the effect of confounding factors such as age, sex, previous CVD events, and left ventricular (LV) dysfunction.

Results
In total, 20 out of 149 patients on MHD (13%) had RV dysfunction. Indexes of their LV function (such as the LV ejection fraction and E/e' ratio) were similar to those of patients without RV dysfunction. During the follow-up period, 23 patients died (7 with RV dysfunction [without LV dysfunction], 3 with LV dysfunction [without RV dysfunction], 2 with biventricular dysfunction, and 11 without any ventricular dysfunction). Kaplan–Meier analyses showed significantly lower survival among patients with RV dysfunction (p < 0.01). The multivariate Cox regression analysis revealed that RV dysfunction (without LV dysfunction) was independently associated with all-cause mortality (hazard ratio: 3.44; 95% confidence interval: 1.28–9.23) after adjusting for confounders.

Conclusions
RV dysfunction is a significant risk factor for all-cause mortality among patients on MHD.
The role of HRM-service quality in the relationship between electronic human resource management and perceived performance
Authors: El Saeed Mariah , Maarouf Heba Mohamed , Younis Raghda Abulsaoud Ahmed 
Published: January 2025

Abstract
Purpose
This research aims to examine how electronic human resource management (E-HRM) impacts perceived organizational performance (OP) and job performance (JP) in telecommunications organizations, with a particular emphasis on the mediating effect of HR service quality (HRSQ).

Research methodology
A questionnaire was developed based on a validated process. Data were collected from 430 employees among the telecommunication companies. However, only 400 questionnaires were valid for the statistical analysis. We use smart PLS and structural equation modeling using Smart PLS v3.2.2 to examine the direct and indirect relationships.

Results and findings
The results of this research revealed that E-HRM has a direct, significant, and positive impact on perceived job performance, as well as organizational performance. Moreover, HRSQ significantly mediates the relationships between E-HRM and job and organizational performance.

Empirical implications
The research introduces empirical several consequences that are discussed later in this paper. The results highlight the importance of designing and implementing E-HRM systems that support organizational workflow and allow employees to do a variety of tasks more efficiently.

Originality
Existing research has shown a link between e-HRM and HR service quality; nonetheless, these studies highlight e-HRM’s potential impact on perceived performance, at both the job and organizational performance levels. The study contributes to the HRM literature by identifying how E-HRM might boost perceived performance by improving HR service quality. As a result, the study serves as a foundation for future theoretical developments in this field.