bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD
Authors: Chen Zhefan Stephen , Ou Mingxi , Taylor Stephanie , Dafinca Ruxandra , Peng Shaohong Isaac , Talbot Kevin , Chan Ho Yin Edwin 
Published: December 2023

AbstractThe GGGGCC hexanucleotide repeat expansion mutation in the chromosome 9 open reading frame 72 (C9orf72) gene is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). In this study, we demonstrate that the zinc finger (ZF) transcriptional regulator Yin Yang 1 (YY1) binds to the promoter region of the planar cell polarity gene Fuzzy to regulate its transcription. We show that YY1 interacts with GGGGCC repeat RNA via its ZF and that this interaction compromises the binding of YY1 to the FuzzyYY1 promoter sites, resulting in the downregulation of Fuzzy transcription. The decrease in Fuzzy protein expression in turn activates the canonical Wnt/β-catenin pathway and induces synaptic deficits in C9ALS/FTD neurons. Our findings demonstrate a C9orf72 GGGGCC RNA-initiated perturbation of YY1–Fuzzy transcriptional control that implicates aberrant Wnt/β-catenin signalling in C9ALS/FTD-associated neurodegeneration. This pathogenic cascade provides a potential new target for disease-modifying therapy.
Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice
Authors: Chen Min , Zhu Jie-Ying , Mu Wang-Jing , Luo Hong-Yang , Li Yang , Li Shan , Yan Lin-Jing , Li Ruo-Ying , Guo Liang 
Published: December 2023

AbstractExercise is an effective non-pharmacological strategy for ameliorating nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism needs further investigation. Cysteine dioxygenase type 1 (Cdo1) is a key enzyme for cysteine catabolism that is enriched in liver, whose role in NAFLD remains poorly understood. Here, we show that exercise induces the expression of hepatic Cdo1 via the cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout of Cdo1 (Cdo1LKO) decreases basal metabolic rate of the mice and impairs the effect of exercise against NAFLD, whereas hepatocyte-specific overexpression of Cdo1 (Cdo1LTG) increases basal metabolic rate of the mice and synergizes with exercise to ameliorate NAFLD. Mechanistically, Cdo1 tethers Camkk2 to AMPK by interacting with both of them, thereby activating AMPK signaling. This promotes fatty acid oxidation and mitochondrial biogenesis in hepatocytes to attenuate hepatosteatosis. Therefore, by promoting hepatic Camkk2-AMPK signaling pathway, Cdo1 acts as an important downstream effector of exercise to combat against NAFLD.
Extending the toolbox for RNA biology with SegModTeX: a polymerase-driven method for site-specific and segmental labeling of RNA
Authors: Haslecker Raphael , Pham Vincent V. , Glänzer David , Kreutz Christoph , Dayie Theodore Kwaku , D’Souza Victoria M. 
Published: December 2023

AbstractRNA performs a wide range of functions regulated by its structure, dynamics, and often post-transcriptional modifications. While NMR is the leading method for understanding RNA structure and dynamics, it is currently limited by the inability to reduce spectral crowding by efficient segmental labeling. Furthermore, because of the challenging nature of RNA chemistry, the tools being developed to introduce site-specific modifications are increasingly complex and laborious. Here we use a previously designed Tgo DNA polymerase mutant to present SegModTeX — a versatile, one-pot, copy-and-paste approach to address these challenges. By precise, stepwise construction of a diverse set of RNA molecules, we demonstrate the technique to be superior to RNA polymerase driven and ligation methods owing to its substantially high yield, fidelity, and selectivity. We also show the technique to be useful for incorporating some fluorescent- and a wide range of other probes, which significantly extends the toolbox of RNA biology in general.
Proteomics-driven noninvasive screening of circulating serum protein panels for the early diagnosis of hepatocellular carcinoma
Authors: Xing Xiaohua , Cai Linsheng , Ouyang Jiahe , Wang Fei , Li Zongman , Liu Mingxin , Wang Yingchao , Zhou Yang , Hu En , Huang Changli , Wu Liming , Liu Jingfeng , Liu Xiaolong 
Published: December 2023

AbstractEarly diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Here, we describe a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 1002 individuals. Machine learning model determined as P4 panel (HABP2, CD163, AFP and PIVKA-II) clearly distinguish HCC from liver cirrhosis (LC, AUC 0.979, sensitivity 0.925, specificity 0.915) and healthy individuals (HC, AUC 0.992, sensitivity 0.975, specificity 1.000) in an independent validation cohort, outperforming existing clinical prediction strategies. Furthermore, the P4 panel can accurately predict LC to HCC conversion (AUC 0.890, sensitivity 0.909, specificity 0.877) with predicting HCC at a median of 11.4 months prior to imaging in prospective external validation cohorts (No.: Keshen 2018_005_02 and NCT03588442). These results suggest that proteomics-driven serum biomarker discovery provides a valuable reference for the liquid biopsy, and has great potential to improve early diagnosis of HCC.
Customizing cellular signal processing by synthetic multi-level regulatory circuits
Authors: Gao Yuanli , Wang Lei , Wang Baojun 
Published: December 2023

AbstractAs synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. Towards this mission, novel regulatory mechanisms and genetic circuits with unprecedented complexity have been implemented over the past decade. These regulatory mechanisms, such as transcription and translation control, could be integrated into hybrid circuits termed “multi-level circuits”. The multi-level circuit design will tremendously benefit the current genetic circuit design paradigm, from modifying basic circuit dynamics to facilitating real-world applications, unleashing our capabilities to customize cellular signal processing and address global challenges through synthetic biology.
MarrowCellDLD: a microfluidic method for label-free retrieval of fragile bone marrow-derived cells
Authors: Porro Gloria , Sarkis Rita , Obergozo Clara , Godot Lucie , Amato Francesco , Humbert Magali , Naveiras Olaia , Guiducci Carlotta 
Published: December 2023

AbstractFunctional bone marrow studies have focused primarily on hematopoietic progenitors, leaving limited knowledge about other fragile populations, such as bone marrow adipocytes (BMAds) and megakaryocytes. The isolation of these cells is challenging due to rupture susceptibility and large size. We introduce here a label-free cytometry microsystem, MarrowCellDLD, based on deterministic lateral displacement. MarrowCellDLD enables the isolation of large, fragile BM-derived cells based on intrinsic size properties while preserving their viability and functionality. Bone marrow adipocytes, obtained from mouse and human stromal line differentiation, as well as megakaryocytes, from primary human CD34+ hematopoietic stem and progenitor cells, were used for validation. Precise micrometer-range separation cutoffs were adapted for each cell type. Cells were sorted directly in culture media, without pre-labeling steps, and with real-time imaging for quality control. At least 106 cells were retrieved intact per sorting round. Our method outperformed two FACS instruments in purity and yield, particularly for large cell size fractions. MarrowCellDLD represents a non-destructive sorting tool for large, fragile BM-derived cells, facilitating the separation of pure populations of BMAds and megakaryocytes to further investigate their physiological and pathological roles.
Relationship between mental health and stressors among fathers of children with chronic illnesses and cognitive structure of fathers’ stress experiences
Authors: Haraguchi Masahiro 
Published: December 2023

AbstractTo clarify the relationship between stressor and mental health of the fathers with children with chronic illnesses and to examine the cognitive structure of fathers’ stress experiences. This study employs a cross-sectional research design. A self-reported questionnaire survey was conducted on 137 respondents. The dependent variables were the stressors of the fathers and depression. Focusing on the data of 51 fathers of children with chronic illness, for 21 items related to the stressful experiences had been identified in a previous study, an exploratory factor analysis using the principal factor method was performed. Logistic regression analysis results showed that the items “There are children with chronic illness” and “The large number of medical treatments required for the children” were significantly associated with the fathers’ poor mental health. In the factor analysis, the following three factors were extracted as a recognition of the fathers’ stress experiences. The fathers positively recognized their role as a father and a husband, perceiving it in a positive light despite their negative feelings. The results also suggested that it should be essential for nurses to re-evaluate those fathers who are exposed to daily stressors as care subjects, as well as to positively include them in the support activities.
Non-myopic multipoint multifidelity Bayesian framework for multidisciplinary design
Authors: Di Fiore Francesco , Mainini Laura 
Published: December 2023

AbstractThe adoption of high-fidelity models in multidisciplinary design optimization (MDO) permits to enhance the identification of superior design configurations, but would prohibitively rise the demand for computational resources and time. Multifidelity Bayesian Optimization (MFBO) efficiently combines information from multiple models at different levels of fidelity to accelerate the MDO procedure. State-of-the-art MFBO methods currently meet two major limitations: (i) the sequential adaptive sampling precludes parallel computations of high-fidelity models, and (ii) the search scheme measures the utility of new design evaluations only at the immediate next iteration. This paper proposes a Non-Myopic Multipoint Multifidelity Bayesian Optimization (NM3-BO) algorithm to sensitively accelerate MDO overcoming the limitations of standard methods. NM3-BO selects a batch of promising design configurations to be evaluated in parallel, and quantifies the expected long-term improvement of these designs at future steps of the optimization. Our learning scheme leverages an original acquisition function based on the combination of a two-step lookahead policy and a local penalization strategy to measure the future utility achieved evaluating multiple design configurations simultaneously. We observe that the proposed framework permits to sensitively accelerate the MDO of a space vehicle and outperforms popular algorithms.
A comprehensive study on criteria of sustainable urban waste management system: using content analysis
Authors: Khosravani Farhad , Abbasi Enayat , Choobchian Shahla , Jalili Ghazizade Mahdi 
Published: December 2023

AbstractThe present study was developed to comprehensively analyze experts' views and content of documents focusing on goals and criteria of sustainable waste management system in Tehran, Iran. To this end, the suitable goals for sustainable waste management system in Tehran city were adopted from domestic, national and international documents. For this purpose, 27 national and international documents and 2 domestic documents related to waste management were selected and analyzed by using content analysis according to Gall, 1994. Further, in order to formulate goals in case of bottlenecks and challenges of waste management in Tehran, the focus group technique was used based on Stewart and Shamdasani, 2014. At this stage, 24 key experts in the field of waste management were interviewed in the form of 4 focus groups. Data collection were performed via audio recording and word-for-word implementation of conversations, taking notes and writing field notes. The data collection continued until reaching theoretical saturation. Next, content analysis and coding methods were used to analyze the data. Finally, the goals of waste management were divided into five general categories including: institutional (with emphasis on the integration and inclusion of the key elements of the urban waste management system), technical and infrastructural (with emphasis on the optimization of existing processes in the use of urban waste management technologies), environmental (with emphasis on minimizing the adverse health and environmental effects of the urban waste management system, economic (with emphasis on the economic and financial sustainability of the urban waste management system), and cultural-social (with emphasis on attracting the maximum participation of citizens and service recipients). The results clearly showed that sustainable waste management measures in Tehran should follow these five components in order to reduce the problems caused by unrealistic waste management and make sustainable use of basic, natural, financial and human resources.
Blocking MyD88 signaling with MyD88 inhibitor prevents colitis-associated colorectal cancer development by maintaining colonic microbiota homeostasis
Authors: Xie Bin , Wang Bo , Shang Runshi , Wang Lu , Huang Xia , Xie Lin 
Published: December 2023

AbstractCertain intestinal microbiota alterations appear to positively correlate with tumorigenesis of CAC due to the disruption of the balance between the host and microorganisms. It is proven that blocking MyD88 signaling can prevent colitis-associated colorectal cancer (CAC) development in mice. We are aim to reveal the role of MyD88 signaling of maintaining colonic microbiota homeostasis for preventing CAC development. We here analyzed the landscape of gut microbiome in the mice model of AOM/DSS-induced CAC with MyD88 inhibitor treatment. PCoA revealed significant reduction in Lactobacillus load and increase in Escherichia load in the mucosal microbial composition of mice with CAC, compared with normal controls (NCs). Inhibitor-treatment led to almost undetectable Proteobacteria (Escherichia) and the retention of the dominance of Firmicutes and Bacteroidota (Muribaculaceae) in the mucosa. RNA sequencing analysis identified genes were up-regulated (Hp, SAA3 and IL-1F9) and down-regulated (CYP3A44, SLC30A10, GPNMB and OTC) in Inhibitor-treated mice (vs. CAC). Meanwhile, Inhibitor-treated mice had higher percentage of MUC2-positive area in colon sections (vs. CAC, which was less than NCs) by IF staining and decreased Escherichia in the mucus layer (vs. CAC) by FISH. And intestinal microbiota from mice with MyD88 inhibitor treatment could lessen the outcome of CAC by fecal microbiota transplantation. The development of CAC was involved in the increasing and ectopic Escherichia in the decreasing colonic mucus layer. MyD88 signaling blockade may maintain the host-microbiota homeostasis by up-regulating MUC2 production, increasing probiotics and their protective effects, and inhibiting the reproduction of Escherichia.
Mathematical model predicts tumor control patterns induced by fast and slow cytotoxic T lymphocyte killing mechanisms
Authors: Wang Yixuan , Bergman Daniel R , Trujillo Erica , Pearson Alexander T. , Sweis Randy F. , Jackson Trachette L. 
Published: December 2023

AbstractImmunotherapy has dramatically transformed the cancer treatment landscape largely due to the efficacy of immune checkpoint inhibitors (ICIs). Although ICIs have shown promising results for many patients, the low response rates in many cancers highlight the ongoing challenges in cancer treatment. Cytotoxic T lymphocytes (CTLs) execute their cell-killing function via two distinct mechanisms: a fast-acting, perforin-mediated process and a slower, Fas ligand (FasL)-driven pathway. Evidence also suggests that the preferred killing mechanism of CTLs depends on the antigenicity of tumor cells. To determine the critical factors affecting responses to ICIs, we construct an ordinary differential equation model describing in vivo tumor-immune dynamics in the presence of active or blocked PD-1/PD-L1 immune checkpoint. Specifically, we identify important aspects of the tumor-immune landscape that affect tumor size and composition in the short and long term. We also generate a virtual cohort of mice with diverse tumor and immune attributes to simulate the outcomes of immune checkpoint blockade in a heterogeneous population. By identifying key tumor and immune characteristics associated with tumor elimination, dormancy, and escape, we predict which fraction of a population potentially responds well to ICIs and ways to enhance therapeutic outcomes with combination therapy.
Implementation of inclusion and exclusion criteria in clinical studies in OHDSI ATLAS software
Authors: Blasini Romina , Buchowicz Kornelia Marta , Schneider Henning , Samans Birgit , Sohrabi Keywan 
Published: December 2023

AbstractClinical trials are essential parts of a medical study process, but studies are often cancelled due to a lack of participants. Clinical Trial Recruitment Support Systems are systems that help to increase the number of participants by seeking more suitable subjects. The software ATLAS (developed by Observational Health Data Sciences and Informatics) can support the launch of a clinical trial by building cohorts of patients who fulfill certain criteria. The correct use of medical classification systems aiming at clearly defined inclusion and exclusion criteria in the studies is an important pillar of this software. The aim of this investigation was to determine whether ATLAS can be used in a Clinical Trial Recruitment Support System to portray the eligibility criteria of clinical studies. Our analysis considered the number of criteria feasible for integration with ATLAS and identified its strengths and weaknesses. Additionally, we investigated whether nonrepresentable criteria were associated with the utilized terminology systems. We analyzed ATLAS using 223 objective eligibility criteria from 30 randomly selected trials conducted in the last 10 years. In the next step, we selected appropriate ICD, OPS, LOINC, or ATC codes to feed the software. We classified each criterion and study based on its implementation capability in the software, ensuring a clear and logical progression of information. Based on our observations, 51% of the analyzed inclusion criteria were fully implemented in ATLAS. Within our selected example set, 10% of the studies were classified as fully portrayable, and 73% were portrayed to some extent. Additionally, we conducted an evaluation of the software regarding its technical limitations and interaction with medical classification systems. To improve and expand the scope of criteria within a cohort definition in a practical setting, it is recommended to work closely with personnel involved in the study to define the criteria precisely and to carefully select terminology systems. The chosen criteria should be combined according to the specific setting. Additional work is needed to specify the significance and amount of the extracted criteria.
Genomic hypomethylation in cell-free DNA predicts responses to checkpoint blockade in lung and breast cancer
Authors: Kim Kyeonghui , Kim Hyemin , Shin Inkyung , Noh Seung-Jae , Kim Jeong Yeon , Suh Koung Jin , Kim Yoo-Na , Lee Jung-Yun , Cho Dae-Yeon , Kim Se Hyun , Kim Jee Hyun , Lee Se-Hoon , Choi Jung Kyoon 
Published: December 2023

AbstractGenomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, it remains unclear whether this approach can be applied to cell-free DNA (cfDNA) and whether it can address the issue of low tumor purity encountered in tissue-based methylation profiling. In this study, we developed an assay named iMethyl, designed to estimate the genomic hypomethylation status from cfDNA. This was achieved through deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n = 167; tissue n = 137; cfDNA early during treatment n = 40), breast cancer (cfDNA n = 91; tissue n = 50; PBMC n = 50; cfDNA at progression n = 44), and ovarian cancer (tissue n = 74). iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. In conclusion, our iMethyl-liquid method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.
Diversity and pathogenic characteristics of the Fusarium species isolated from minor legumes in Korea
Authors: Ha Min Sun , Ryu Hyunjoo , Ju Ho Jong , Choi Hyo-Won 
Published: December 2023

AbstractLegumes are primarily grown agriculturally for human consumption, livestock forage, silage, and as green manure. However, production has declined primarily due to fungal pathogens. Among them, this study focused on Fusarium spp. that cause Fusarium wilt in minor legumes in Korea. Diseased legume plants were collected from 2020 to 2021, and diverse fungal genera were isolated from the internal tissues of the plant roots and stems. Fusarium spp. were the most dominant, accounting for 71% of the isolates. They were identified via morphological characteristics and molecular identification. In the pathogenicity test, Fusarium oxysporum and Fusarium fujikuroi generally exhibited high virulence. The host range investigation revealed that the NC20-738, NC20-739, and NC21-950 isolates infected all nine crops, demonstrating the widest host range. In previous studies, the focus was solely on Fusarium wilt disease in soybeans. Therefore, in this study, we aimed to investigate Fusarium wilt occurred in minor legumes, which are consumed as extensively as soybeans, due to the scarcity of data on the diversity and characteristics of Fusarium spp. existing in Korea. The diverse information obtained in this study will serve as a foundation for implementing effective management strategies against Fusarium-induced plant diseases.