bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nomogram model for predicting invasive placenta in patients with placenta previa: integrating MRI findings and clinical characteristics
Authors: Huang Fang , Lyu Guo-Rong , Lai Qing-Quan , Li Yuan-Zhe 
Published: January 2024

AbstractThis study aims to validate a nomogram model that predicts invasive placenta in patients with placenta previa, utilizing MRI findings and clinical characteristics. A retrospective analysis was conducted on a training cohort of 269 patients from the Second Affiliated Hospital of Fujian Medical University and a validation cohort of 41 patients from Quanzhou Children’s Hospital. Patients were classified into noninvasive and invasive placenta groups based on pathological reports and intraoperative findings. Three clinical characteristics and eight MRI signs were collected and analyzed to identify risk factors and develop the nomogram model. The mode’s performance was evaluated in terms of its discrimination, calibration, and clinical utility. Independent risk factors incorporated into the nomogram included the number of previous cesarean sections ≥ 2 (odds ratio [OR] 3.32; 95% confidence interval [CI] 1.28–8.59), type-II placental bulge (OR 17.54; 95% CI 3.53–87.17), placenta covering the scar (OR 2.92; CI 1.23–6.96), and placental protrusion sign (OR 4.01; CI 1.06–15.18). The area under the curve (AUC) was 0.908 for the training cohort and 0.803 for external validation. The study successfully developed a highly accurate nomogram model for predicting invasive placenta in placenta previa cases, based on MRI signs and clinical characteristics.
The local variation of the Gaussian modulus enables different pathways for fluid lipid vesicle fusion
Authors: Bottacchiari Matteo , Gallo Mirko , Bussoletti Marco , Casciola Carlo Massimo 
Published: January 2024

AbstractViral infections, fertilization, neurotransmission, and many other fundamental biological processes rely on membrane fusion. Straightforward calculations based on the celebrated Canham–Helfrich elastic model predict a large topological energy barrier that prevents the fusion process from being thermally activated. While such high energy is in accordance with the physical barrier function of lipid membranes, it is difficult to reconcile with the biological mechanisms involved in fusion processes. In this work, we use a Ginzburg–Landau type of free energy that recovers the Canham–Helfrich model in the limit of small width-to-vesicle-extension ratio, with the additional ability to handle topological transitions. We show that a local modification of the Gaussian modulus in the merging region both dramatically lowers the elastic energy barrier and substantially changes the minimal energy pathway for fusion, in accordance with experimental evidence. Therefore, we discuss biological examples in which such a modification might play a crucial role.
The long-term effects of heated tobacco product exposure on the central nervous system in a mouse model of prodromal Alzheimer's disease
Authors: Yamada Hidetada , Yamazaki Yu , Takebayashi Yoshiko , Yazawa Kyosuke , Sasanishi Miwako , Motoda Atsuko , Nakamori Masahiro , Morino Hiroyuki , Takahashi Tetsuya , Maruyama Hirofumi 
Published: January 2024

AbstractHeated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS.
Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions
Authors: Pinheiro Inês , Calo Nicolas , Paolini-Bertrand Marianne , Hartley Oliver 
Published: January 2024

AbstractThe chemokine receptor CCR5 is known to exist in cell surface subpopulations that differ in their capacity to engage ligands. One proposed explanation for this phenomenon is the presence of CCR5 species with different levels of post-translational modifications (PTMs). Tyrosine sulfation and O-glycan sialylation are PTMs that add negative charges to the extracellular domain of CCR5 and make strong contributions to chemokine binding but it is not known whether cellular mechanisms to control their levels exist. In this study we used a combination of sulfation-sensitive and sulfation-insensitive CCR5 ligands to show that the rate of turnover of CCR5 tyrosine sulfation is more rapid than the rate of turnover of the receptor itself. This suggests that the steady state level of CCR5 sulfation is maintained through the combination of tyrosine protein sulfotransferase (TPST), the trans-Golgi network (TGN)-resident ‘source enzyme, and a ‘sink’ activity that removes tyrosine sulfation from CCR5. By measuring the effects on ligand binding of knockdown and overexpression experiments, we provided evidence that non-lysosomal cellular arylsulfatases, particularly ARSG, ARSI and ARSJ, are CCR5 sulfation ‘sink’ enzymes. We also used targeted knockdown and sialylation-sensitive and insensitive chemokines to identify the sialidase NEU3 as a candidate ‘sink’ enzyme for CCR5 O-glycan sialylation. This study provides the first experimental evidence of activity of sulfatase and sialidase ‘sink’ enzymes on CCR5, providing a potential mechanism for cells to control steady-state levels of these PTMs and thereby exert dynamic control over receptor-ligand interactions at the cell surface and during receptor desensitization.
Exploring shared therapeutic targets in diabetic cardiomyopathy and diabetic foot ulcers through bioinformatics analysis
Authors: Wu Hanlin , Yang Zheming , Wang Jing , Bu Yuxin , Wang Yani , Xu Kai , Li Jing , Yan Chenghui , Liu Dan , Han Yaling 
Published: January 2024

AbstractAdvanced diabetic cardiomyopathy (DCM) patients are often accompanied by severe peripheral artery disease. For patients with DCM combined with diabetic foot ulcer (DFU), there are currently no good therapeutic targets and drugs. Here, we investigated the underlying network of molecular actions associated with the occurrence of these two complications. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. We performed enrichment and protein–protein interaction analyses, and screened for hub genes. Construct transcription factors (TFs) and microRNAs regulatory networks for validated hub genes. Finally, drug prediction and molecular docking verification were performed. We identified 299 common differentially expressed genes (DEGs), many of which were involved in inflammation and lipid metabolism. 6 DEGs were identified as hub genes (PPARG, JUN, SLC2A1, CD4, SCARB1 and SERPINE1). These 6 hub genes were associated with inflammation and immune response. We identified 31 common TFs and 2 key miRNAs closely related to hub genes. Interestingly, our study suggested that fenofibrate, a lipid-lowering medication, holds promise as a potential treatment for DCM combined with DFU due to its stable binding to the identified hub genes. Here, we revealed a network involves a common target for DCM and DFU. Understanding these networks and hub genes is pivotal for advancing our comprehension of the multifaceted complications of diabetes and facilitating the development of future therapeutic interventions.
Targeting HDACs for diffuse large B-cell lymphoma therapy
Authors: Wu Chunyan , Song Qiao , Gao Sophie , Wu Shaoling 
Published: January 2024

AbstractHistone deacetylases (HDACs) are involved in tumorigenesis and progression, however, their role in diffuse large B-cell lymphoma (DLBCL) is not well understood. In this study, we examined the expression levels, mutations, and clinical significance of HDACs in DLBCL. Additionally, we investigated the therapeutic potential of Chidamide, a novel HDAC inhibitor, to provide scientific evidence for targeting HDACs in DLBCL patients. We extracted transcriptome data of DLBCLs––including 47 lymph node samples and 337 whole-blood-cell controls––from The Cancer Genome Atlas. Bioinformatic analyses of HDAC expression, mutation, and correlation with the clinical significance of DLBCL patients were performed with the Gene Expression Profiling Interactive Analysis, GENEMANIA, and web-based software including cBioPortal and WebGestalt. To examine the therapeutic effect of Chidamide, DLBCL cell lines (WSU-DLCL-2 and DB cells) were employed. Cell proliferation and apoptosis were analyzed with Cell Counting Kit-8 and flow cytometry assays. The impact of Chidamide treatment was also analyzed by RNA sequencing of treated DB cells. Western blot was used to explore the molecular mechanism of the cytotoxicity of Chidamide on DLBCL cell lines. The expression of some HDACs (HDAC1, 2, 3, 4, 6, 7, 8, and 9) were significantly higher in the lymph node samples of DLBCL than that in whole-blood-cell controls. Moreover, we found that the mutation rate of HDACs was also higher in DLBCL tissues, although the overall survival of DLBCL patients was not associated with HDAC expression. Chidamide was found to have a cytotoxic effect on DLBCL cells in a dose-dependent manner, while transcriptome analysis and western blot revealed that using it for treatment impacted several biological processes, including PI3K/AKT signaling, mTOR signaling, the cell cycle, and apoptosis pathways. Alterations of HDAC genes, including enhanced expression and mutations, are positively related to DLBCL. Targeting HDACs with specific inhibitors such as Chidamide may represent a potential therapeutic approach for DLBCL patients.
Community-based prevalence and associated factors of sarcopenia in the Vietnamese elderly
Authors: Pham Lan-Anh Thi , Nguyen Binh Thanh , Huynh Dao Tieu , Nguyen Binh-Minh Le Thi , Tran Phuong-Anh Nhat , Van Vo Tam , Bui Hy-Han Thi , Thai Truc Thanh 
Published: January 2024

AbstractSarcopenia, a condition characterized by muscle mass decline, is one of the leading health problems in the elderly. This study determined the rate of sarcopenia according to criteria by Asian Working Group for Sarcopenia (AWGS) and related factors in elderly people. A community-based cross-sectional study was conducted in 632 people aged 60 years or over in Ho Chi Minh City. Data were collected through a predefined questionnaire and direct measurement. Sarcopenia was identified based on the Inbody 770 machine and AWGS criteria. The prevalence of sarcopenia was 32.0%. Participants with advanced age, low education, unemployment, low level of family economics and frailty were more likely to have sarcopenia. Among these, frailty had the highest impact on sarcopenia, with significantly higher odds of having sarcopenia found in participants with pre-frailty (OR = 4.80, 95% CI 2.75–8.38, p < 0.001) and frailty (OR = 21.16, 95% CI 8.96–49.97, p < 0.001). In contrast, BMI was inversely associated with sarcopenia. Sarcopenia is prevalent in the Vietnamese elderly. Apart from social demographic characteristics including age, education, employment and family economic status, frailty appeared to be an important risk factor. Early screening, referral, and treatment of sarcopenia among the elderly having a high risk of sarcopenia are recommended.
Geodetic imaging of magma ascent through a bent and twisted dike during the Tajogaite eruption of 2021 (La Palma, Canary Islands)
Authors: Przeor Monika , Castaldo Raffaele , D’Auria Luca , Pepe Antonio , Pepe Susi , Sagiya Takeshi , Solaro Giuseppe , Tizzani Pietro , Barrancos Martínez José , Pérez Nemesio 
Published: January 2024

AbstractOn Sept. 19th, 2021, the largest historical eruption on the island of La Palma began, which had a significant scientific, social, and economic impact. The 2021 Tajogaite eruption was characterised by short precursors, lasting only 8 days. The seismicity started on Sept. 11th with a westward and upward migration of hypocenters. Permanent GNSS stations started recording deformation on Sept. 12th on the island's western side, which reached more than 15 cm just before the eruption. After the eruption onset, the ground deformation increased, reaching a maximum on Sept. 22nd and showing a nearly steady deflation trend in the following months. To better understand the dynamics of the eruption, we exploited a joint dataset of GNSS and Sentinel-1 SBAS time series along both ascending and descending orbits. To obtain the geometry of the causative source of the ground deformation, we combined the result of a preliminary non-linear inversion and the precise location of the seismicity. The resulting geometry of the source is that of a twisted dike bending eastward. We performed inverse modelling to obtain the spatiotemporal kinematics of the opening function of the dike. The forward modelling has been realised using a 3D finite-element approach considering the island's topography. Our findings reveal a close correspondence between the magmatic intrusion and pre-eruptive seismicity. The ascent of the magma occurred along two branches, and the rheology of a previously identified ductile layer strongly affected the magma propagation process. Finally, we found evidence of an early shallow deformation, which we interpret as the effect of ascending hydrothermal fluids. Our findings highlight the need for advanced modelling to understand pre-eruptive processes in basaltic volcanoes.
Association between metabolites in tryptophan-kynurenine pathway and inflammatory bowel disease: a two-sample Mendelian randomization
Authors: Yu Fangqian , Du Yutong , Li Cong , Zhang Haiyan , Lai Weiming , Li Sheng , Ye Zhenhao , Fu Wenbin , Li Shumin , Li Xiang-Guang , Luo Ding 
Published: January 2024

AbstractPrevious observational studies have suggested an association between tryptophan (TRP)–kynurenine (KYN) pathway and inflammatory bowel disease (IBD). However, whether there is a causal relationship among them remains unclear. Therefore, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effects of crucial metabolites in TRP–KYN pathway on IBD and its subtypes. Using summary data from genome-wide association studies, a two-sample MR was employed to evaluate the genetic associations between TRP and KYN as exposures and IBD as an outcome. The inverse variance weighted method was used as the primary MR analysis, with MR-Egger, weighted mode, simple mode, and weighted median methods as complementary analyses. The odds ratios (OR) and 95% confidence intervals (CI) were determined for TRP–IBD (OR 0.739, 95% CI [0.697; 0.783]), TRP–UC (OR 0.875, 95% CI [0.814; 0.942]), TRP–CD (OR 0.685, 95% CI [0.613; 0.765]), KYN–IBD (OR 4.406, 95% CI [2.247; 8.641]), KYN–UC (OR 2.578, 95% CI [1.368; 4.858], and KYN–CD (OR 13.516, 95% CI [4.919; 37.134]). Collectively, the MR analysis demonstrated a significant protective association between TRP and IBD, whereas KYN was identified as a risk factor for IBD.
Pinpointing top inhibitors for GSK3β from pool of indirubin derivatives using rigorous computational workflow and their validation using molecular dynamics (MD) simulations
Authors: Pandya Vamangi , Rao Priyashi , Prajapati Jignesh , Rawal Rakesh M. , Goswami Dweipayan 
Published: January 2024

AbstractGlycogen synthase kinase-3β (GSK3β) is a pivotal protein kinase implicated in a spectrum of debilitating diseases, encompassing cancer, diabetes, and neurodegenerative disorders. While the therapeutic potential of GSK3β inhibition is widely recognized, there remains an unmet need for a rigorous, systematic analysis probing the theoretical inhibition dynamics of a comprehensive library of indirubin derivatives against GSK3β using advanced computational methodologies. Addressing this gap, this study embarked on an ambitious endeavor, leveraging indirubin—a renowned scaffold—as a template to curate a vast library of 1000 indirubin derivatives from PubChem. These were enriched with varied substitutions and modifications, identified via a structure similarity search with a Tanimoto similarity threshold of 85%. Harnessing a robust virtual screening workflow, we meticulously identified the top 10 contenders based on XP docking scores. Delving deeper, we gauged the binding free energy differentials (ΔGBind) of these hits, spotlighting the top three compounds that showcased unparalleled binding prowess. A comparative pharmacophore feature mapping with the reference inhibitor OH8, co-crystallized with GSK3β (PDB ID: 6Y9R), was undertaken. The binding dynamics of these elite compounds were further corroborated with 100 ns molecular dynamics simulations, underlining their stable and potent interactions with GSK3β. Remarkably, our findings unveil that these indirubin derivatives not only match but, in certain scenarios, surpass the binding affinity and specificity of OH8. By bridging this research chasm, our study amplifies the therapeutic promise of indirubin derivatives, positioning them as frontrunners in the quest for groundbreaking GSK3β inhibitors, potentially revolutionizing treatments for a myriad of ailments.
Alterations in mitochondria isolated from peripheral blood mononuclear cells and tumors of patients with epithelial ovarian cancers
Authors: Charoenkwan Kittipat , Apaijai Nattayaporn , Sriwichaiin Sirawit , Chattipakorn Nipon , Chattipakorn Siriporn C. 
Published: January 2024

AbstractMetabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.
Short- and long-term effects of essential oils on swine spermatozoa during liquid phase refrigeration
Authors: Troisio Ilaria , Bertocchi Martina , Ventrella Domenico , Scozzoli Maurizio , Di Vito Maura , Truzzi Eleonora , Benvenuti Stefania , Mattarelli Paola , Bacci Maria Laura , Elmi Alberto 
Published: January 2024

AbstractThe application of essential oils as potential alternatives to antibiotics in swine semen storage is promising, due to their antioxidant and antibacterial properties. However, detrimental effects on spermatozoa should be clarified first. The aim of this study was to evaluate 9 essential oils (EOs; Satureja montana, Pelargonium graveolens, Cymbopogon nardus, Melaleuca leucadendron, Eucaliptus globulus, Citrus limon, Lavandula angustifolia, Lavandula hybrida, Mentha piperita) and a blend (GL mix) on key morpho-functional parameters of swine spermatozoa. Test compounds were firstly chemo-characterized and experimental doses were prepared by suspending a fixed number of spermatozoa with 3 different concentrations (0.1, 0.5, 1 mg/mL) of EOs. Experimental doses were stored at 16 °C and sampled after 3 and 120 h for analysis. Overall, S. montana, P. graveolens and L. angustifolia EOs induced the strongest alterations, with C. nardus and E. globulus EOs being the best tolerated. Swine spermatozoa represent a good preliminary testing platform to screen toxicity and its different patterns. The comprehensive overview on the potential mechanisms of action of some of the most common EOs, despite of the direct aim of the study being swine reproduction, may be exploited in other fields of research within both veterinary and human medicine.
Stepwise reduction of graphene oxide and studies on defect-controlled physical properties
Authors: Das Poulomi , Ibrahim Sk , Chakraborty Koushik , Ghosh Surajit , Pal Tanusri 
Published: January 2024

AbstractGraphene oxide (GO) is a monolayer of oxidized graphene which is a convenient and potential candidate in a wide range of fields of applications like electronics, photonics, optoelectronics, energy storage, catalysis, chemical sensors, and many others. GO is often composed of various oxygen-containing groups such as hydroxyl, carboxyl, and epoxy. One appealing method for achieving graphene-like behavior with sp2 hybridized carbon is the reduction of GO i.e. formation of reduced graphene oxide (RGO). A stepwise reduction GO to form a family of RGO, containing various quantities of oxygen-related defects was carried out. Herein, the defects related chemical and physical properties of GO and the RGO family were studied and reported in an effort to understand how the properties of RGO vary with the reduction rate. Although there are several reports on various features and applications of GO and RGO but a systematic investigation of the variation of the physical and chemical properties in RGO with the varying quantities of oxygeneous defects is imperative for the engineered physical properties in achieving the desired field of applications. We have attempted to look at the role of sp2 and sp3 carbon fractions, which are present in RGO-based systems, and how they affect the electrical, optoelectronic, and adsorption characteristics.