bluuebunny/crossref_metadata_2025_split huggingface dataset:
The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma
Authors: Liu Zhiyuan , Wang Songtao , Yu Kuo , Chen Kaile , Zhao Liang , Zhang Jiayue , Dai Kexiang , Zhao Peng 
Published: November 2023

Abstract
Background
Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression.

Methods
Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2ʹ-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays.

Results
The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2.

Conclusion
Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.
Finite element analyses of three minimally invasive fixation techniques for treating Sanders type II intra-articular calcaneal fractures
Authors: Song Guoxun , Gu Wenqi , Shi Zhongmin , Li Xueqian , Fu Shaoling , Yu Xiaowei , Song Facheng 
Published: November 2023

AbstractBackground and objectiveCalcaneal Sanders type II or III fractures are highly disabling with significant burden. Surgical treatment modalities include open reduction and internal fixation (ORIF) techniques and a variety of minimally invasive surgical (MIS) approaches. ORIF techniques are associated with complications and traditional MIS techniques need extensive intraoperative fluoroscopic procedures. The present study aims to investigate the effects of three different minimally invasive internal fixation (MIIF) techniques used to treat Sanders type II intra-articular calcaneal fractures using finite element analyses.MethodsA 64-row spiral computed tomography scan was used to observe the calcaneus of a healthy adult. The scanning data were imported into Mimics in a DICOM format. Using a new model of a Sanders type II-B intra-articular calcaneal fracture, three minimally invasive techniques were simulated. Technique A involved fixation using an isolated minimally invasive locking plate; Technique B used a minimally invasive locking plate with one medial support screw; and Technique C simulated a screw fixation technique using four 4.0-mm screws. After simulating a 640-N load on the subtalar facet, the maximum displacement and von Mises stress of fragments and implants were recorded to evaluate the biomechanical stability of different fixation techniques using finite element analyses.ResultsAfter stress loading, the maximum displacements of the fragments and implants were located at the sustentaculum tali and the tip of sustentaculum tali screw, respectively, in the three techniques; however, among the three techniques, Technique B had better results for displacement of both. The maximum von Mises stress on the fragments was < 56 Mpa, and stress on the implants using the three techniques was less than the yield strength,with Technique C having the least stress.ConclusionAll three techniques were successful in providing a stable fixation for Sanders type II intra-articular calcaneal fractures, while the minimally invasive calcaneal locking plate with medial support screw fixation approach exhibited greater stability, leading to improved enhancement for the facet fragment; however, screw fixation dispersed the stress more effectively than the other two techniques.
Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer
Authors: Tan Zheqiong , Deme Pragney , Boyapati Keerti , Claes Britt S. R. , Duivenvoorden Annet A. M. , Heeren Ron M. A. , Tressler Caitlin M. , Haughey Norman James , Glunde Kristine 
Published: November 2023

Abstract
Background
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC.

Methods
We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples.

Results
Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3β and MAPK signaling.

Conclusions
Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.
Chromatin balances cell redox and energy homeostasis
Authors: Suganuma Tamaki , Workman Jerry L. 
Published: November 2023

AbstractChromatin plays a central role in the conversion of energy in cells: alteration of chromatin structure to make DNA accessible consumes energy, and compaction of chromatin preserves energy. Alteration of chromatin structure uses energy sources derived from carbon metabolism such as ATP and acetyl-CoA; conversely, chromatin compaction and epigenetic modification feedback to metabolism and energy homeostasis by controlling gene expression and storing metabolites. Coordination of these dual chromatin events must be flexibly modulated in response to environmental changes such as during development and exposure to stress. Aging also alters chromatin structure and the coordination of metabolism, chromatin dynamics, and other cell processes. Noncoding RNAs and other RNA species that associate directly with chromatin or with chromatin modifiers contribute to spatiotemporal control of transcription and energy conversion. The time required for generating the large amounts of RNAs and chromatin modifiers observed in super-enhancers may be critical for regulation of transcription and may be impacted by aging. Here, taking into account these factors, we review alterations of chromatin that are fundamental to cell responses to metabolic changes due to stress and aging to maintain redox and energy homeostasis. We discuss the relationship between spatiotemporal control of energy and chromatin function, as this emerging concept must be considered to understand how cell homeostasis is maintained.
A phenome-wide scan reveals convergence of common and rare variant associations
Authors: Zhou Dan , Zhou Yuan , Xu Yue , Meng Ran , Gamazon Eric R. 
Published: November 2023

Abstract
Background
Common and rare variants contribute to the etiology of complex traits. However, the extent to which the phenotypic effects of common and rare variants involve shared molecular mediators remains poorly understood. The question is essential to the basic and translational goals of the science of genomics, with critical basic-science, methodological, and clinical consequences.

Methods
Leveraging the latest release of whole-exome sequencing (WES, for rare variants) and genome-wide association study (GWAS, for common variants) data from the UK Biobank, we developed a metric, the COmmon variant and RAre variant Convergence (CORAC) signature, to quantify the convergence for a broad range of complex traits. We characterized the relationship between CORAC and effective sample size across phenome-wide association studies.

Results
We found that the signature is positively correlated with effective sample size (Spearman ρ = 0.594, P < 2.2e − 16), indicating increased functional convergence of trait-associated genetic variation, across the allele frequency spectrum, with increased power. Sensitivity analyses, including accounting for heteroskedasticity and varying the number of detected association signals, further strengthened the validity of the finding. In addition, consistent with empirical data, extensive simulations showed that negative selection, in line with enhancing polygenicity, has a dampening effect on the convergence signature. Methodologically, leveraging the convergence leads to enhanced association analysis.

Conclusions
The presented framework for the convergence signature has important implications for fine-mapping strategies and drug discovery efforts. In addition, our study provides a blueprint for the expectation from future large-scale whole-genome sequencing (WGS)/WES and sheds methodological light on post-GWAS studies.
Deciphering the role of extrachromosomal circular DNA in adipose stem cells from old and young donors
Authors: Ren Sen , Wu Du , Shen Xiaoyong , Wu Qian , Li Chengcheng , Xiong Hewei , Xiong Zhongwei , Gong Rui , Liu Zheng , Wang Wei , Chen Jincao 
Published: November 2023

Abstract
Background
The functional impairment of adipose stem cells (ASCs) during aging limits their clinical transformation. Studies have shown that extrachromosomal circular DNAs (eccDNAs) are associated with tumor progression and cell aging, but the roles of eccDNAs in ASCs remain unknown.

Method
We conducted Circle sequencing (Circle-seq) to identify eccDNAs in ASCs isolated from young and old donors. The differentially expressed eccDNAs were calculated, annotated and validated via polymerase chain reaction.

Results
Thousands of eccDNAs were identified and comprehensively characterized. Most of them were GC-rich, < 1000 base pairs in size, and were enriched on chromosome 19 and 17 with a high density of Alu elements and genes, 2 kb upstream/downstream of genes and satellites. In total, 3025 eccDNAs were differentially expressed among the two ASC groups. Conjoint analysis of the Circle-seq results and previous RNA-seq results revealed that 73 eccDNAs and 55 genes exhibited the same differential expression between the two groups. KEGG and GO analyses revealed that genes encoding differentially expressed eccDNAs were enriched for cell adhesion, cellular senescence and TGF-β receptor signaling pathway. We also found that aged ASCs exhibited loss of eccDNAs, including CAMK2G (chr10: 75577899-75578176), TRABD2B (chr1: 48305638-48307008) and TRABD2B (chr1: 48305425-48307091).

Conclusion
In this study, we elucidated the first eccDNA profile relating to ASCs and demonstrated that three eccDNAs are lost in aged ASCs, which may be potential biomarkers of stem cell aging and valuable targets for stem cell rejuvenation.
Anesthetic management of a huge retroperitoneal leiomyoma: a case report
Authors: Shi Yue , Zhu Bo , Zhang Yu , Huang Yuguang 
Published: November 2023

Abstract
Background
Retroperitoneal leiomyomas are rare, with just over 100 cases reported in the literature. Perioperative management of retroperitoneal leiomyomas can be challenging due to the large tumor size and the risk of hemorrhage.

Case presentation
We report a case of a 40-year-old Han woman with a 40-cm retroperitoneal leiomyoma. General anesthesia was performed for the surgical resection. Key flow parameters like cardiac output and stroke volume variation, as shown by the Vigileo™-FloTrac™ system, enabled the anesthesiologist to implement goal-directed fluid optimization. Acute normovolemic hemodilution and cell salvage technique were used resulting in a successful en bloc tumor resection with a 6000-mL estimated blood loss. Although the patient experienced postoperative bowel obstruction, no other significant complications were observed.

Conclusion
Advanced hemodynamic monitoring and modern patient blood management strategies are particularly helpful for anesthetic management of huge retroperitoneal leiomyomas.
EFL teachers’ cognition of social and psychological consequences of high-stake national language tests: role of teacher training workshops
Authors: Allahyari Rahmatolah , Abbasabady Mahmoud Moradi , Akhter Shamim , Alibakhshi Goudarz 
Published: November 2023

AbstractConsequential validity, a facet of construct validity, has been extensively explored by educational psychologists and scholars focused on English language assessment. It is widely recognized that English language instructors must possess a thorough understanding of high-stake language tests. However, the body of research concerning EFL teachers’ perceptions of high-stake tests is quite limited. This study aims to delve into the cognitions of Iranian EFL teachers regarding the social and psychological ramifications of high-stake English language tests. Additionally, the study investigates the influence of a teacher training workshop on EFL teachers’ perceptions of test consequences. The research employs a two-phase quantitative research design. A total of 210 EFL teachers participated in the survey, completing a scale comprising 25 items that delineated their perceptions of test consequences. Furthermore, thirty teachers engaged in a two-session workshop focused on test consequences. Data analysis encompassed both one-sample and paired-sample t tests.The results reveal that EFL teachers possess knowledge regarding certain social and psychological consequences of language tests; however, their awareness of some adverse consequences remains limited. Notably, the outcomes indicate that teacher training workshops have a positive impact on teachers’ cognitions of both positive and negative test consequences. The implications of these findings extend to teacher trainers and English language educators, offering practical insights to enhance the effectiveness of their teaching practices.
Thermochronology of hydrothermal alteration zones in the Kii Peninsula, southwest Japan: an attempt for detecting the thermal anomalies and implications to the regional exhumation history
Authors: Sueoka Shigeru , Iwano Hideki , Danhara Tohru , Niwa Masakazu , Kanno Mizuho , Kohn Barry P. , Kawamura Makoto , Yokoyama Tatsunori , Kagami Saya , Ogita Yasuhiro , Hirata Takafumi 
Published: November 2023

AbstractFluid-inclusion and thermochronometric analyses have been applied to hydrothermal alteration zones and their host rocks outcropping in the Hongu area of the Kii Peninsula, southwestern Japan in an attempt to detect thermal anomalies related to hydrothermal events and quantify the thermal effects on the host rocks. Hydrothermal events at ~ 150 °C and ~ 200 °C were identified by fluid-inclusion microthermometry of quartz veins in the alteration zones. For the host rocks and alteration zones, in the youngest population zircon yielded U–Pb dates ranging between ~ 74.7–59.2 Ma, fission-track dates of ~ 27.2–16.6 Ma, and (U–Th)/He single-grain dates of ~ 23.6–8.7 Ma. Apatite yielded pooled fission-track ages of ~ 14.9–9.0 Ma. The zircon U–Pb dates constrain the maximum depositional ages of the sedimentary samples. However, the fission-track and (U–Th)/He dates show no clear trend as a function of distance from the alteration zones. Hence, no thermal anomaly was detected in the surrounding host rocks based on the thermochronometric data patterns. The fission-track and (U–Th)/He dates are rather thought to record regional thermal and exhumation histories rather than a direct thermal imprint of fluid flow, probably because the duration of such activity was too short or because fluid flow occurred before regional cooling events and were later thermally overprinted. Apatite fission-track ages of ~ 10 Ma may reflect regional mountain uplift and exhumation related to the obduction of the SW Japan lithospheric sliver onto the Shikoku Basin, or the rapid subduction of the Philippine Sea slab associated with the clockwise rotation of the Southwest Japan Arc.
Graphical Abstract
Self-diagnose is associated with knowledge and attitude towards mental illness of university students in Indonesia
Authors: Ismail Naufal Arif , Kusumaningtyas Intan , Firngadi Moetrarsi Sri Kanapsijah 
Published: November 2023

Abstract
Background
Mental illness is still stigmatized and poorly understood in Indonesian society, but university students could be a key target for promoting positive attitudes and increasing awareness. This study aims to explore the knowledge and attitudes of university students in Indonesia toward mental illness and to identify associated factors, emphasizing self-diagnosis.

Method
An analytical cross-sectional study on university students in Yogyakarta, Indonesia, was conducted from September to November 2022. Participants completed an online questionnaire about their sociodemographic data, mental health knowledge (utilized Mental Health Knowledge Schedule questionnaire), and attitudes toward mental illness (utilized Community Attitude to Mental Illness Inventory questionnaire). Univariate, bivariate, and multivariate logistic regression were performed to analyze collected data.

Results
A total of 402 university students were included in the study. Results demonstrated that half of the students had good mental illness knowledge (50.7%), and slightly more than half had favorable attitudes (53.0%). Self-diagnosis was significantly associated with poorer knowledge and negative attitudes (adjusted odds ratio [AOR]: 2.31, 95% confidence interval [CI] 1.19 to 4.50 and AOR: 2.12, 95% CI 1.13 to 3.99; P < 0.05, respectively). Additionally, students who had never studied psychology or psychiatry and had a family mental illness history were at higher risk (P < 0.05) for poor knowledge of mental illness (AOR: 2.24, 95% CI 1.18 to 4.25 and AOR: 1.82, 95% CI 1.00 to 3.30, respectively). Interestingly, students with lower monthly family incomes had more positive attitudes (AOR: 0.39, 95% CI 0.18 to 0.86; P < 0.05). A very weak negative correlation (ρ = − 0.173; P < 0.001) between mental illness knowledge and attitudes was observed.

Conclusion
Promoting awareness and knowledge about mental health, as well as preventing self-diagnosis, is crucial in addressing the lack of knowledge and negative attitudes toward mental illness among university students in Indonesia, which is expected to play a role in the wider community ultimately.
Investigation of barium sulphate shielding during panoramic radiography
Authors: Bawazeer Omemh , Fallatah Alaa , Alasmary Mohamed , Bokhary Younis , Almerabi Areej , Khan Suha , Abuhadi Nouf , Alalawi Amani , Asiri Naseem , Bawazir Saeed , Al-Qahtani Saeed , Algethami Merfat , Badawy Mohamed 
Published: November 2023

Abstract
Background
Radiation shielding in radiology has historically been achieved with lead; however, there has been an increasing demand for radiation shielding to be more environmentally friendly. Barium has shown promise as a substitute in many radiology applications. This study aims to investigate a barium sulphate shield in protecting the thyroid and the eye lens during panoramic radiography.

Methods
During a simulated panoramic examination, an anthropomorphic phantom and a solid-state detector measured the radiation dose to the surface thyroid and the eye lens. The measurements were taken using no shield and a barium sulphate shield. A Welch's T-test was employed to compute the shield's effect on radiation. Two radiologists assessed the image quality with and without the thyroid shields.

Results
The dose reduction was between 66 and 75% for the barium shield at the thyroid. The dose reduction ranged between 15 and 61% in the eye region. Images using a barium shield were deemed adequate for diagnostic interpretation.

Conclusions
Barium shields effectively reduce the radiation dose in the thyroid region during panoramic radiography without degrading image quality. The dose reduction depends on the tube voltage and the area of interest.
Revealing Sexual Dimorphism in Prolactin Regulation From Early Postnatal Development to Adulthood in Murine Models
Authors: Abeledo-Machado Alejandra , Peña-Zanoni Milagros , Bornancini Dana , Díaz-Torga Graciela 
Published: November 2023

Abstract
Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to age-matched males. This pattern has traditionally been attributed to the development and maturation of endocrine and neuroendocrine networks responsible for regulating PRL synthesis and secretion. However, the effect of dopamine (DA), which acts as an inhibitory factor on lactotroph function, also increases from birth to puberty, particularly in females. Nonetheless, the secretion of PRL remains higher in females compared to males. On the other hand, the observed sex differences in serum PRL levels during early postnatal development cannot be attributed to the influence of estradiol (E2). While serum E2 levels gradually increase after birth, only after 45 days of life do the disparities in E2 levels between females and males become evident. These observations collectively suggest that neither the maturation of hypothalamic DA regulation nor the rise in E2 levels can account for the progressive and sustained elevation in serum PRL levels and the observed sexual dimorphism during postnatal development. This review highlights the importance of recent discoveries in animal models that shed light on inhibitory mechanisms in the control of PRL secretion within the pituitary gland itself, that is intrapituitary mechanisms, with a specific emphasis on the role of transforming growth factor β1 and activins in PRL secretion.