bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy
Authors: Bakhshi Parisa , Nourizadeh Maryam , Sharifi Laleh , Farajollahi Mohammad M. , Mohsenzadegan Monireh 
Published: November 2023

Abstract
Background
Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system’s ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated promise in eliciting a tumor-specific immune response. In this study, we investigated the potential of using DCs loaded with the MAGE-A2 long peptide to activate T cell cytotoxicity toward PCa cell lines.

Methods
Here, we generated DCs from monocytes and thoroughly characterized their phenotypic and functional properties. Then, DCs were pulsed with MAGE-A2 long peptide (LP) as an antigen source, and monitored for their transition from immature to mature DCs by assessing the expression levels of several costimulatory and maturation molecules like CD14, HLA-DR, CD40, CD11c, CD80, CD83, CD86, and CCR7. Furthermore, the ability of MAGE-A2 -LP pulsed DCs to stimulate T cell proliferation in a mixed lymphocyte reaction (MLR) setting and induction of cytotoxic T cells (CTLs) in coculture with autologous T cells were examined. Finally, CTLs were evaluated for their capacity to produce interferon-gamma (IFN-γ) and kill PCa cell lines (PC3 and LNCaP).

Results
The results demonstrated that the antigen-pulsed DCs exhibited a strong ability to stimulate the expansion of T cells. Moreover, the induced CTLs displayed substantial cytotoxicity against the target cells and exhibited increased IFN-γ production during activation compared to the controls.

Conclusions
Overall, this innovative approach proved efficacious in targeting PCa cell lines, showcasing its potential as a foundation for the development and improved PCa cancer immunotherapy.
Influence of renal function on the ability of TyG Index to predict all-cause mortality
Authors: Li Huilan , Chen Weihua , Lin Xueqin , Chen Weiqin , Xie Tingzheng , Chen Kaihong , Hou Shuhong , Li Huaqing 
Published: November 2023

Abstract
Background
The association between triglyceride–glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies.

Methods
This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either < 60 mL/min/1.73m2 or ≥ 60 mL/min/1.73m2), participants were categorized into four distinct groups: (1) TyG_L/eGFR_H; (2) TyG_H/eGFR_H; (3) TyG_L/eGFR_L; and (4) TyG_H/eGFR_L. The endpoint was the all-cause mortality rate. Standard Kaplan–Meier plots were constructed and multifactor Cox regression analyses were carried out and restricted cubic spline regression analysis was utilized to assess the association between death and the TyG index for different renal function statuses.

Results
No statistical differences were found in the TyG groups in participants with normal renal function after adjustment for all covariates (P = 0.070). However, in the high TyG index group with renal insufficiency, the risk of all-cause mortality rates was reduced by 18%. (HR, 0.82; CI, 0.69–0.98). The TyG index (high vs. low) and renal function (eGFR < 60 vs. eGFR ≥ 60) had statistically significant interactions with death (P < 0.001). When all covariates were adjusted, the risk of mortality for the TyG_L combined with eGFR_L group was 56% higher than that for the TyG_L combined with eGFR_H group (HR, 1.56; CI, 1.33–1.82). In the renal insufficiency population, a nonlinear relationship was observed between mortality and the TyG index, albeit with a differing pattern (P for nonlinearity < 0.001).

Conclusions
While it has been known that TyG index was a prognosis marker of CVD, this research highlights that higher TyG index was associated with higher all-cause mortality rates for all participants. Furthermore, renal function status significantly moderates the effect of the TyG index on all-cause mortality in community-dwelling adults.
Enhancing lettuce yield via Cu/Fe-layered double hydroxide nanoparticles spraying
Authors: Wu Hongyang , Wan Xiaoyang , Niu Jiefei , Xu Huimin , Zhang Yu , Xue Xian , Li Yang , Li Qiang , Lu Tao , Yu Hongjun , Jiang Weijie 
Published: November 2023

AbstractLayered double hydroxides (LDHs) have been widely used in the field of plant engineering, such as DNA/RNA transformation and enhancing plant disease resistance. However, few studies have examined the direct effects of LDHs on plants and their potential utility as nanofertilizers. In this study, the retention capacity of Cu/Fe-layered double hydroxide nanoparticles (CuFe-LDHs) was assessed by comparative experiments on vegetables. The results showed that the retention of CuFe-LDHs in leafy vegetables was high, such as lettuce. Phenotypic analysis revealed that the fresh and dry weights of lettuce leaves were both increased by spraying 10–100 μg/mL CuFe-LDHs. Using the optimal concentration of 10 μg/mL, we conducted further experiments to elucidate the mechanism of CuFe-LDHs promoting lettuce growth. It was found that the application of CuFe-LDHs had a significant effect on growth and induced physiological, transcriptomic, and metabolomic changes, including an increase in the chlorophyll b content, net photosynthetic rate, and intercellular carbon dioxide concentration, as well as modifications in gene expression patterns and metabolite profiles. This work provides compelling evidence that CuFe-LDHs can efficiently adsorb on the surface of lettuce leaves through hydrogen bonding, promote lettuce growth, mitigate the toxicity of heavy metal ions compared to their raw materials at the same concentration and offer a molecular-scale insight into the response of leafy vegetables to CuFe-LDHs.
Graphical Abstract
Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study
Authors: Chang Hsun , Kuo Chien-Feng , Yu Teng-Shun , Ke Liang-Yin , Hung Chung-Lieh , Tsai Shin-Yi 
Published: November 2023

Abstract
Background
Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan’s National Health Insurance Research Database.

Methods
From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made.

Results
The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person‐years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47–1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05).

Conclusion
Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.
Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic stroke
Authors: Liu Pin-yi , Li Hui-qin , Dong Meng-qi , Gu Xin-ya , Xu Si-yi , Xia Sheng-nan , Bao Xin-yu , Xu Yun , Cao Xiang 
Published: November 2023

Abstract
Background
Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear.

Methods
Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein–protein interactions, and related signaling pathways, etc.

Results
The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation.

Conclusion
Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.
In-depth quantification of bimanual coordination using the Kinarm exoskeleton robot in children with unilateral cerebral palsy
Authors: Decraene Lisa , Orban de Xivry Jean-Jacques , Kleeren Lize , Crotti Monica , Verheyden Geert , Ortibus Els , Feys Hilde , Mailleux Lisa , Klingels Katrijn 
Published: November 2023

AbstractBackgroundRobots have been proposed as tools to measure bimanual coordination in children with unilateral cerebral palsy (uCP). However, previous research only examined one task and clinical interpretation remains challenging due to the large amount of generated data. This cross-sectional study aims to examine bimanual coordination by using multiple bimanual robotics tasks in children with uCP, and their relation to task execution and unimanual performance.MethodsThe Kinarm exoskeleton robot was used in 50 children with uCP (mean age: 11 years 11 months ± 2 years 10 months, Manual Ability Classification system (MACS-levels: l = 27, ll = 16, lll = 7)) and 50 individually matched typically developing children (TDC). All participants performed three tasks: object-hit (hit falling balls), ball-on-bar (balance a ball on a bar while moving to a target) and circuit task (move a cursor along a circuit by making horizontal and vertical motions with their right and left hand, respectively). Bimanual parameters provided information about bimanual coupling and interlimb differences. Differences between groups and MACS-levels were investigated using ANCOVA with age as covariate (α < 0.05,$${\upeta }_{p}^{2}$$ηp2). Correlation analysis (r) linked bimanual coordination to task execution and unimanual parameters.ResultsChildren with uCP exhibited worse bimanual coordination compared to TDC in all tasks (p ≤ 0.05,$${\eta }_{p}^{2}$$ηp2 = 0.05–0.34). The ball-on-bar task displayed high effect size differences between groups in both bimanual coupling and interlimb differences (p < 0.001,$${\eta }_{p}^{2}$$ηp2 = 0.18–0.36), while the object-hit task exhibited variations in interlimb differences (p < 0.001,$${\eta }_{p}^{2}$$ηp2 = 0.22–0.34) and the circuit task in bimanual coupling (p < 0.001,$${\eta }_{p}^{2}$$ηp2 = 0.31). Mainly the performance of the ball-on-bar task (p < 0.05,$${\eta }_{p}^{2}$$ηp2 = 0.18–0.51) was modulated by MACS-levels, showing that children with MACS-level lll had worse bimanual coordination compared to children with MACS-level l and/or II. Ball-on-bar outcomes were highly related to task execution (r = − 0.75–0.70), whereas more interlimb differences of the object-hit task were moderately associated with a worse performance of the non-dominant hand (r = − 0.69–(− 0.53)).ConclusionThis study gained first insight in important robotic tasks and outcome measures to quantify bimanual coordination deficits in children with uCP. The ball-on-bar task showed the most discriminative ability for both bimanual coupling and interlimb differences, while the object-hit and circuit tasks are unique to interlimb differences and bimanual coupling, respectively.
Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan
Authors: Muhammad Noor , Azeem Ayesha , Arif Shumaila , Naeemi Humaira , Masood Iqra , Hassan Usman , Ijaz Bushra , Hanif Faisal , Syed Aamir Ali , Yusuf Muhammed Aasim , Rashid Muhammad Usman 
Published: November 2023

Abstract
Background
BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.

Methods
One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls.

Results
Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers.

Conclusions
In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.
Cross-alteration of murine skin and tick microbiome concomitant with pathogen transmission after Ixodes ricinus bite
Authors: Boulanger Nathalie , Insonere Jean-Louis-Marie , Van Blerk Sebastian , Barthel Cathy , Serres Céline , Rais Olivier , Roulet Alain , Servant Florence , Duron Olivier , Lelouvier Benjamin 
Published: November 2023

Abstract
Background
Ticks are major vectors of diseases affecting humans such as Lyme disease or domestic animals such as anaplasmosis. Cross-alteration of the vertebrate host skin microbiome and the tick microbiome may be essential during the process of tick feeding and for the mechanism of pathogen transmission. However, it has been poorly investigated.

Methods
We used mice bitten by field-collected ticks (nymphs and adult ticks) in different experimental conditions to investigate, by 16S rRNA gene metabarcoding, the impact of blood feeding on both the mouse skin microbiome and the tick microbiome. We also investigated by PCR and 16S rRNA gene metabarcoding, the diversity of microorganisms transmitted to the host during the process of tick bite at the skin interface and the dissemination of the pathogen in host tissues (blood, heart, and spleen).

Results
Most of the commensal bacteria present in the skin of control mice were replaced during the blood-feeding process by bacteria originating from the ticks. The microbiome of the ticks was also impacted by the blood feeding. Several pathogens including tick-borne pathogens (Borrelia/Borreliella, Anaplasma, Neoehrlichia, Rickettsia) and opportunistic bacteria (Williamsia) were transmitted to the skin microbiome and some of them disseminated to the blood or spleen of the mice. In the different experiments of this study, skin microbiome alteration and Borrelia/Borreliella transmission were different depending on the tick stages (nymphs or adult female ticks).

Conclusions
Host skin microbiome at the bite site was deeply impacted by the tick bite, to an extent which suggests a role in the tick feeding, in the pathogen transmission, and a potentially important impact on the skin physiopathology. The diversified taxonomic profiles of the tick microbiome were also modified by the blood feeding.
Uterine microbial communities and their potential role in the regulation of epithelium cell cycle and apoptosis in aged hens
Authors: Dai Dong , Wang Jing , Zhang Haijun , Wu Shugeng , Qi Guanghai 
Published: November 2023

Abstract
Background
Alterations of the uterine microbiome are closely associated with various intrauterine diseases and physiological conditions, which are well-established in mammals. However, as representative oviparous animals, the research on the uterine microbial ecosystem and its functions with physiological homeostasis is limited in chickens. Additionally, continuous egg-laying disrupts the oviducal immune defenses of aged hens, susceptible to pathogen invasion, causing poor egg quality and food-borne infections in humans. Here, we investigated aging-related changes in the oviduct microbial colonization and transmission from the gut to eggs and their roles in a hen model.

Results
The results of 16S rDNA sequencing showed significant differences in the oviduct microbial composition between young (38 weeks) and aged (77 weeks) laying hens. SourceTracker analysis further revealed differences in the effects of microbial transmission on the oviducal microbiota between young and aged hens. Enhanced barrier defense with cell apoptosis suppression and cell cycle arrest of the uterus were observed in aged hens reducing microbial transmission from the lower to upper reproductive tract. In addition, a total of 361 significantly differential metabolites were identified using metabolomics in the aged uterine microbiota, especially in products of amino acid metabolism and biosynthesis of various secondary metabolites, which might have essential effects on cell apoptosis by regulating immune responses and cell cycle. Notably, antibiotics disrupted uterine microbiota by dietary intervention and direct perfusion did not retard aging-related physiological changes but further aggravated aging processes by disrupting the cell cycle and apoptosis.

Conclusions
The microbiota continuum along the reproductive tract in aged birds differs from that in young birds, especially with a significant shift in the uterus. The aged uterine microbiota probably contributes to the regulation of cell cycle and apoptosis by microbial metabolites primarily involved in amino acid metabolism and biosynthesis of various secondary metabolites. These findings provide new insights into the roles of the reproductive tract microbiota in regulating the cell programming of the aged host, contributing to the exploration of the microbiome as a target for diagnosing aging health status and therapy for gynecological diseases in women.
Big Data Analytics-based life cycle sustainability assessment for sustainable manufacturing enterprises evaluation
Authors: Tamym Lahcen , Benyoucef Lyes , Nait Sidi Moh Ahmed , El Ouadghiri Moulay Driss 
Published: November 2023

AbstractRecently, governments and organizations have repeatedly pressed manufacturing enterprises to promote the ethical and transparent use of natural resources, lessen their negative effects on national and international ecosystems, and safeguard people and the environment. In this context, enhancing the various stages of the product/service life cycle to fulfill sustainability requirements and foster sustainable value creation is a key area of interest for researchers and professionals. This emphasis reflects the growing recognition of the importance of minimizing the environmental impact of products and services, while also maximizing their positive contributions to society, economy, and environment. To this end, this research work addresses how manufacturing enterprises benefit from life cycle sustainability assessment (LCSA) thinking to incorporate the environmental and social criteria into the product/service life cycle strategies. To do so, a novel approach based on environmental priority strategy (EPS) as an LCSA method for impacts monetization coupling with Big Data Analytics (BDA) techniques and tools is developed to evaluate and analyze the manufacturing enterprises’ impacts on the environment and society. Moreover, the developed approach evaluates manufacturing enterprises’ progress toward sustainable development goals (SDGs). Finally, to demonstrate the applicability of the developed approach, a case study from the corporate environmental impact database is used, and the obtained numerical results are analyzed showing its efficiency and added value.