bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bioinformatics-Driven ceRNA Network in Stomach Adenocarcinoma: Identification of Novel Prognostic mRNA-miRNA-lncRNA Interactions
Authors: Kamal Ebtihal , Omar Zainab Mohammed Mahmoud , Geddawy Ayman , Omer Ahmad AA 
Published: December 2024

AbstractStomach adenocarcinoma is a major contributor to worldwide mortality and poses a substantial challenge to improving life expectancy. The main objective of the current work was to identify diagnostic and prognostic biomarkers in stomach adenocarcinoma in order to advance translational medicine and patient outcomes. By accomplishing this objective, the research seeks to provide significant insights into the field of translational medicine. Seven novel unfavourable prognosis-associated genes (NALCN, CALCR, CPT1C, ELAVL3, FLJ16779, MYOZ3, and TPST1) were first identified. Additionally, 41 potential miRNAs were predicted. ELAVL3-hsa-mir-29a-3p and CALCR-hsa-mir-29a-3p axes were identified as two critical pathways in the carcinogenesis of stomach adenocarcinoma via a bioinformatics analysis. Following that, lncRNAs binding to hsa-mir-29a-3p were predicted via starBase and miRNet databases for predicting lncRNA binding sites. After conducting both expression and survival analyses for these predicted lncRNAs, we found that only one lncRNA (KCNQ1OT1) was markedly overexpressed in stomach adenocarcinoma, and its elevated expression was associated with an unfavourable prognosis. Next, we established a comprehensive mRNA-miRNA-lncRNA triple ceRNA network linked to the prognosis of patients with stomach adenocarcinoma. In summary, the current study provides an extensive ceRNA network that highlights novel diagnostic and prognostic biomarkers for stomach adenocarcinoma.
Suppression of PCBP1 Enhances PPARγ via TAK1 Modulation to Improve Glycemic and Lipid Metabolism Disorders in Gestational Diabetes Mellitus
Authors: Xia Xuemei , Chen Yan 
Published: December 2024

AbstractGestational diabetes mellitus (GDM) affects the health of pregnant women and their fetuses. Poly(C)-binding protein 1 (PCBP1), a multifunctional RNA-binding protein, is pivotal in maintaining cytosolic iron homeostasis. This study sheds light on the role and mechanism of PCBP1 in glucose and lipid metabolism dysregulation in GDM via a high-fat diet-induced GDM mouse model and a palmitic acid (PA)-triggered insulin resistance(IR) model in HepG2 cells. Glucose tolerance and insulin tolerance tests were performed in GDM mice, with lipid metabolism evaluated via hematoxylin-eosin (HE) staining, Oil Red O staining, as well as biochemical assay kits. Glucose content was quantified using the glucose oxidase method, while cell viability was evaluated trough the CCK-8 assay. Apoptotic activity was examined through TUNEL staining, and the expression levels of key proteins, including phosphorylated AKT (p-AKT), phosphorylated IRS1 (p-IRS1), PCBP1, TAK1, and PPARγ, were analyzed through Western blotting. The results demonstrated that GDM mice exhibited profound glucose and lipid metabolism disorders, characterized by significant lipid droplet accumulation in hepatic cells and disrupted insulin signaling pathways. Furthermore, hepatic expression of PCBP1 and TAK1 was notably upregulated, whereas PPARγ expression was significantly reduced. In vitro experiments revealed that silencing PCBP1 alleviated glucose and lipid metabolism abnormalities and improved insulin signaling in PA-induced insulin-resistant HepG2 (IR-HepG2) cells. This intervention also enhanced cell viability and suppressed apoptosis. Further mechanistic studies indicated that inhibition of TAK1 expression facilitated PPARγ upregulation, while TAK1 overexpression negated these effects. Additionally, silencing PPARγ in TAK1-silenced cells reversed the metabolic improvements in IR-HepG2 cells, whereas overexpression of PPARγ mitigated the adverse effects of PCBP1 overexpression. The foregoing findings demonstrate that PCBP1 exerts its effects on glucose and lipid metabolism in GDM via the TAK1/PPARγ signaling axis. Our study highlights the important function of the PCBP1/TAK1/PPARγ signaling pathway in mediating glucose and lipid metabolism in GDM, providing valuable insights into possible therapeutic targets for GDM treatment.
The Way Home: A Scoping Review of Public Health Strategies to Increase the Utilization of Home Dialysis in Chronic Kidney Disease Patients
Authors: Yongphiphatwong Natcha , Teerawattananon Yot , Supapol Pitsinee , Pandejpong Denla , Chuanchaiyakul Tanainan , Sutawong Jiratorn , Gandhi Naline , Kiatkrissada Nutthawongse , Dabak Saudamini Vishwanath , Anothaisintawee Thunyarat 
Published: December 2024

ABSTRACTIntroductionHome dialysis (HoD) remains underutilized, despite evidence showing it provides comparable mortality rates to in-center hemodialysis (ICHD) while offering advantages such as improved quality of life and lower overall costs. This scoping review comprehensively evaluates the impact of public health interventions on increasing the use of HoD, including both Peritoneal Dialysis (PD) and Home Hemodialysis (HHD).MethodsRelevant studies were searched in the Web of Science, Medline, Embase, Scopus, EBSCOhost, and EconLit databases from their inception through May 2024. Studies were eligible for review if they assessed the effectiveness of public health interventions in terms of utilization and retention rates for general HoD, PD, and HHD.ResultsForty-three studies were included, with interventions categorized into three main types: educational programs, service provision improvements, and modifications to payment structures. Our findings indicate that educational interventions—aimed at enhancing knowledge about dialysis options and promoting shared decision-making among patients, families, and healthcare providers—and service provision improvements, such as assisted PD and nephrologist-performed catheter insertions, could significantly increase the initiation, utilization, and retention rates of HoD. However, the impact of payment interventions on HoD outcomes differed across different contexts.ConclusionEducation and service provision enhancements may represent the most effective public health interventions for increasing initiation, utilization, and retention rates of HoD in dialysis requiring patients. However, these findings are predominantly based on evidence from observational studies; further experimental studies with rigorous methodology are warranted to validate the effectiveness of these interventions in promoting HoD utilization.PLAIN TEXT SUMMARYKidney dialysis is a life-sustaining therapy that can be offered both at home and in medical centres, however, home dialysis is underutilised globally. This scoping review gathers evidence from around the world to identify and assess the effectiveness of public health interventions to improve home dialysis utilization. The interventions we found were mainly related to improving patient knowledge, redesigning service provision, or adjusting payment/reimbursement conditions. Our results suggest that educating patients about their dialysis options to support shared decision-making before they require dialysis and offering assisted peritoneal dialysis at home can help increase the number of patients starting and staying on home dialysis. However, adjusting payment and reimbursement policies showed mixed results.
MentalQLM: A lightweight large language model for mental healthcare based on instruction tuning and dual LoRA modules
Authors: Shi Jiayu , Wang Zexiao , Zhou Jiandong , Liu Chengyu , Sun Poly Z.H. , Zhao Erying , Lu Lei 
Published: December 2024

AbstractMental disorders present significant challenges to healthcare systems and carry profound social consequences. The rapid development of large language model (LLM) has opened new avenues for enhancing mental healthcare. However, existing approaches primarily rely on instruction tuning and few-shot in-context learning with massive datasets and large-scale backbone models, resulting in significant computational costs. To address these challenges, we propose MentalQLM, a novel lightweight LLM by developing a new dual Low-rank Adaptation (LoRA) approach. The development of MentalQLM consists of two key stages. Firstly, datasets are pruned based on perplexity and diversity analysis to reduce computational requirements. The first LoRA module is instruction-tuned to adapt the LLM for downstream mental health classification tasks. Secondly, a dense layer augmented with a second LoRA module is fine-tuned to enhance performance on complex multi-class classification tasks. Extensive experiments validate the effectiveness of the proposed MentalQLM on five benchmark datasets. Despite having only 0.5B parameters, the model outperforms or demonstrates comparable performance to larger counterparts in both classification and reasoning tasks. This establishes MentalQLM as a promising solution for lightweight and efficient deployment in realworld mental healthcare applications. All the code will be released athttps://github.com/tortorish/MentalQLM.
Transcriptomic regulation of juvenile-to-adult vegetative phase transition in grapevine
Authors: Ferradás Yolanda , Royo Carolina , Martínez-Zapater José Miguel , Lijavetzky Diego 
Published: December 2024

AbstractPlants go through two distinct stages in their vegetative phase, with the juvenile stage being characterized by a lack of maturity to respond to flowering induction stimuli and the adult stage marked by the presence of this capacity. Phase transition has been extensively analysed in herbaceous species such as Arabidopsis and maize, where the sequential activity of miR156 and miR172 in the control of the juvenile to adult phase transition has been determined. Contrarily, little is known about most woody perennial crops, where phase transition appears to be dissociated, with a first transition from juvenile to adult vegetative state in the first year and a subsequent induction to flower in later years under flowering-inductive environmental conditions. This significantly extended vegetative phase makes fruit production depend on the grafting of adult vegetative materials. A particular aspect of grapevine vegetative phase transition is that it is marked by the differentiation of tendrils, a modified sterile reproductive organ adapted to climbing, which is continuously generated with different patterns in differentVitisspecies. When the grapevine plant reaches flowering inductive condition in later years, it produces inflorescences in place of some tendrils. As a first step to understand the regulation of phase change in grapevine, we have performed a detailed gene expression analysis of the juvenile-to-adult phase transition during the development of grapevine plantlets grown from seeds. The RNA-seq analysis demonstrated that miR156 was significantly repressed in the grapevine’s adult phase, where the appearance of tendrils acts as a marker of the transition. Consistent with the results reported in other species, we observed the activation of severalSPLgenes, known to be targets of miR156, providing evidence for the conservation of the miR156-SPLs regulatory module in grapevine. However, no variation was detected in the expression of miR172 andTPSgenes were found downregulated, two key determinants in the transition to flowering in other species. This could be explained considering that grapevines do not flower during the first years of growth. Interestingly, we were able to observe the overexpression of several genes known to be involved in the establishment of flower meristem identity, which in the case of grape had also been detected along tendril development, consistent with the proposed common ontogenetic origin of tendrils and inflorescences in theVitaceaefamily.
Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport
Authors: Wojcechowskyj Jason A , Jong Robyn M , Mäger Imre , Flach Britta , Munson Paul V , Mukherjee Pragya , Mertins Barbara , Barcay Katherine R , Folliard Thomas 
Published: December 2024

ABSTRACTSelf-amplifying RNA (saRNA)-based vaccines have emerged as a potent and durable RNA vaccine platform. However, RNA vaccine platforms trigger undesirable side effects at protective doses, underscoring the need for improved tolerability. To address this, we leveraged the Cardiovirus leader protein, which is well-characterized to dampen host innate signaling by modulating nucleocytoplasmic transport (NCT). Co-administration of a leader-protein-encoding mRNA (which we have named “RNAx”) delivered alongside vaccine cargo saRNA reduced interferon production while enhancing Influenza hemagglutinin (HA) expression in human primary cells and murine models. RNAx potently decreased serum biomarkers of reactogenicity after immunizations with an HA-expressing saRNA-LNP vaccine while maintaining the magnitude of the antibody and cellular response. RNAx also consistently enhanced binding antibody titers after a single injection and in some conditions enhanced binding antibody and neutralization titers post-boost. These findings support RNAx as a promising platform approach for improving tolerability of saRNA-LNP vaccines while preserving or enhancing immunogenicity.
Discovery of disease-associated cellular states using ResidPCA in single-cell RNA and ATAC sequencing data
Authors: Carver Shaye , Taraszka Kodi , Groha Stefan , Gusev Alexander 
Published: December 2024

AbstractTo enhance understanding of cellular heterogeneity and disease from single-cell sequencing data, we introduce ResidPCA, a robust method for cell state identification that models cell type heterogeneity. Simulations demonstrate ResidPCA’s efficacy, particularly in complex scenarios, with its accuracy more than four times higher than conventional Principal Component Analysis (PCA) and over three times higher than Non-negative Matrix Factorization (NMF)-based methods in identifying states expressed across multiple cell types. In scRNA-seq data from light-stimulated mouse visual cortex cells, ResidPCA captures stimulus-driven variability with an accuracy more than five times higher than NMF methods. In single nucleus data from an Alzheimer’s disease cohort, ResidPCA identified 44 snATAC-based and 42 snRNA-based states. 30 snATAC states were significantly enriched for Alzheimer’s disease heritability and were often more significantly enriched than established cell types such as microglia. The ResidPCA-based snATAC state most significantly enriched for Alzheimer’s disease heritability further elucidates a recently identified mechanism involving the neuron-ODC-microglial axis. This state links early amyloid production in neurons and oligodendrocytes with later-stage microglial activation and immune response, driving Alzheimer’s disease progression. These results demonstrate ResidPCA’s ability to reveal additional biological variation in single-cell data and uncover disease-relevant cell states.
Transcriptional Dosage of Oncogenic KRAS Drives Lung Adenocarcinoma Cell States, Progression and Metastasis
Authors: Serresi Michela , Cetin Ali Osman , Dramaretska Yuliia , Kertalli Sonia , Schmitt Matthias J. , Naumann Heike , Zschummel Maria , Liesse-Labat Marie , Maciel Lucas F. , Declercq Jeroen , Marine Jean-Christophe , Gargiulo Gaetano 
Published: December 2024

AbstractCancer cells display distinct, recurrent phenotypic cell states. Metastatic spreading correlates with tumor cell state evolution. However, the molecular mechanisms underlying metastasis remain elusive. Here, we demonstrate that the quantitative dosage of oncogenic KRAS drives lung adenocarcinoma progression and metastasis via the integration of external signaling and pioneer transcription factor dynamics into qualitative cell states. Combining mouse models, in vivo CRISPR activation screens, and fate mapping, we show that even mild transcriptional amplification of KRAS significantly fuels tumor progression and metastasis. Chromatin profiling and transcriptomics reveal that high and low KRAS dosages supersede and integrate inflammatory and TGFβ signaling to dictate mouse cancer cell states. Patient data show that KRAS dosages correlate with distinct survival outcomes, transcription factor activity, and cell states. Direct KRAS inhibition in xenografts limits the KRAS-high “proliferative” cell state but spares a minimal residual state mimicking the KRAS-low “ciliated-like” state. Thus, oncogenic KRAS dosage fuels tumor heterogeneity at the cell state level and drives a bimodal tumor evolution during metastasis, with implications for prognosis and treatment.
Comprehensive Assessment of a Fasting-Mimicking Diet: Salivary Metabolite Profiles, Weight Loss, and Biomarker Analysis
Authors: Hof Kevin Sebastiaan , Wall Christopher Tadhg 
Published: December 2024

SummaryFasting-mimicking diets (FMDs) have shown to result in various health benefits, including body weight reduction, body fat reduction, decreased blood pressure and longevity promoting effects through enhanced ketogenesis and reduced glycolysis. The direct impact of FMDs on metabolite fluctuations, however, remains elusive. Here, we explore the effects of FMDs on the human salivary metabolic profiles and weight in a single-arm case study. Specifically, we present a bio-energetic framework to estimate fat loss as a component of the sustained weight loss, the effects on metabolite quantities involved in energetic reprogramming and the effects on the abundance of metabolites originating from the gut microbiome. These findings highlight the importance of metabolic health tracking to further our understanding of the effects of fasting, personalized nutrition and effective preventive health measures.In briefHof & Wall demonstrate that fasting-mimicking diets have short-term effects on the energy production, energetic reprogramming and gut microbiome output in humans by use of saliva metabolomics and nuclear magnetic resonance (NMR).Highlights45% of total sustained weight loss could be attributed to fat loss as calculated by bio-energetic calculation frameworkFasting-mimicking diets increase L-glutamine, L-glutamate and succinic acid indicating immediate effects on energy metabolismFasting-mimicking diets increase short-chain fatty acids i.e. acetate, butyrate and propionate. Other gut microbiome metabolites are increased as well i.e. acetoin, fucose and ethanol.
Direct and abscopal anti-tumor responses elicited by peripheral nerve schwannoma irradiation synergize with anti-PD1 treatment in vestibular schwannoma models
Authors: Yin Zhenzhen , Lu Simeng , Wu Limeng , Sun Yao , Blake David W. , Chen Jie , Landegger Lukas D. , Ho William , Xiu Bingyu , Jones Adam P. , Muzikansky Alona , Shih Helen A. , Stankovic Konstantina M. , Plotkin Scott R. , Xu Lei 
Published: December 2024

AbstractNF2-related schwannomatosis (NF2-SWN) is a progressive and disabling disease requiring effective treatments. The hallmark ofNF2-SWN is bilateral vestibular schwannomas (VSs), which progressively enlarge, leading to permanent sensorineural hearing loss and severely impacting patients’ quality of life. Currently, there are no FDA-approved drugs for VS or the associated hearing loss. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but have not yet been systematically investigated in non-malignant tumors such as VS. In our studies, we demonstrated that combining anti-PD1 (αPD1) treatment with radiation therapy (RT) provides three significant therapeutic benefits: i) Enhanced αPD1 efficacy and immune memory: RT induces immunogenic cell death and activates the STING pathway, enhancing αPD1 efficacy and generating long-term immune memory, ii) Reduced RT dose and associated tissue injury: The combination strategy reduces the required RT dose necessary for effective tumor control, potentially minimizing RT injury to surrounding normal tissues, and iii) Elicited abscopal effects on cerebellopontine angle (CPA) schwannomas: RT to peripheral nerve tumor induces a systemic abscopal effect, which synergizes with αPD-1 to effectively control intracranial schwannomas without direct irradiation, sparing the cochlea from radiation exposure and avoiding auditory radiation injury. Together, our findings provide a compelling rationale for deploying ICIs in combination with radiotherapy as a novel treatment approach for patients with VS andNF2-SWN.
Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe
Authors: Rohrbach Daniel J. , Carter Kevin A. , Luo Dandan , Shao Shuai , Aygun-Sunar Semra , Lovell Jonathan F. , Sunar Ulas 
Published: December 2024

AbstractLiposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Pre-liminary results validate the probe effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer by optimizing chemotherapy administration with precision and control.
Loss of SynDIG4/PRRT1 alters distribution of AMPA receptors in Rab4- and Rab11-positive endosomes and impairs basal AMPA receptor recycling
Authors: He Chun-Wei , Díaz Elva 
Published: December 2024

ABSTRACTThe transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synapse plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear. In this study, we characterized the endocytosis and recycling of GluA1-containing AMPARs under basal conditions. We did not observe any change in baseline endocytosis; however, we did observe a significant decrease in recycling of GluA1-containing AMPARs in cultured hippocampal neurons from mice lacking SynDIG4. This resulted in a significant increase in the levels of internal GluA1 and GluA2, along with greater colocalization of these subunits with Rab4-positive recycling endosomes in hippocampal neurons lacking SynDIG4. Notably, the overlap between Rab4- and Rab11-positive vesicles was elevated in hippocampal neurons lacking SynDIG4, suggesting an impairment in the trafficking between Rab4 and Rab11 compartments. Furthermore, our findings revealed a reduction in surface GluA1 within synaptic regions of hippocampal neurons lacking SynDIG4. Collectively, these results indicate that SynDIG4 regulates the distribution of GluA1-containing AMPARs via the Rab4-dependent endosomal recycling pathway, thereby maintaining AMPAR levels at synaptic regions under baseline conditions. This regulatory function of SynDIG4 may contribute to the deficits in GluA1-dependent synaptic plasticity and impairment of hippocampal-dependent learning and memory behaviors observed in SynDIG4 deficient mice.