bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronological Age Prediction: Developmental Evaluation of DNA Methylation-Based Machine Learning Models
Authors: Fan Haoliang , Xie Qiqian , Zhang Zheng , Wang Junhao , Chen Xuncai , Qiu Pingming 
Published: January 2022

Epigenetic clock, a highly accurate age estimator based on DNA methylation (DNAm) level, is the basis for predicting mortality/morbidity and elucidating the molecular mechanism of aging, which is of great significance in forensics, justice, and social life. Herein, we integrated machine learning (ML) algorithms to construct blood epigenetic clock in Southern Han Chinese (CHS) for chronological age prediction. The correlation coefficient (r) meta-analyses of 7,084 individuals were firstly implemented to select five genes (ELOVL2, C1orf132, TRIM59, FHL2, and KLF14) from a candidate set of nine age-associated DNAm biomarkers. The DNAm-based profiles of the CHS cohort (240 blood samples differing in age from 1 to 81 years) were generated by the bisulfite targeted amplicon pyrosequencing (BTA-pseq) from 34 cytosine-phosphate-guanine sites (CpGs) of five selected genes, revealing that the methylation levels at different CpGs exhibit population specificity. Furthermore, we established and evaluated four chronological age prediction models using distinct ML algorithms: stepwise regression (SR), support vector regression (SVR-eps and SVR-nu), and random forest regression (RFR). The median absolute deviation (MAD) values increased with chronological age, especially in the 61–81 age category. No apparent gender effect was found in different ML models of the CHS cohort (all p &gt; 0.05). The MAD values were 2.97, 2.22, 2.19, and 1.29 years for SR, SVR-eps, SVR-nu, and RFR in the CHS cohort, respectively. Eventually, compared to the MAD range of the meta cohort (2.53–5.07 years), a promising RFR model (ntree = 500 and mtry = 8) was optimized with an MAD of 1.15 years in the 1–60 age categories of the CHS cohort, which could be regarded as a robust epigenetic clock in blood for age-related issues.
Application of Perinatal Derivatives in Ovarian Diseases
Authors: Lange-Consiglio Anna , Capra Emanuele , Herrera Valentina , Lang-Olip Ingrid , Ponsaerts Peter , Cremonesi Fausto 
Published: January 2022

Reproductive diseases could lead to infertility and have implications for overall health, most importantly due to psychological, medical and socio-economic consequences for individuals and society. Furthermore, economical losses also occur in animal husbandry. In both human and veterinary medicine, hormonal and surgical treatments, as well as assisted reproductive technologies are used to cure reproductive disorders, however they do not improve fertility. With ovarian disorders being the main reproductive pathology in human and bovine, over the past 2 decades research has approached regenerative medicine in animal model to restore normal function. Ovarian pathologies are characterized by granulosa cell and oocyte apoptosis, follicular atresia, decrease in oocyte quality and embryonic development potential, oxidative stress and mitochondrial abnormalities, ultimately leading to a decrease in fertility. At current, application of mesenchymal stromal cells or derivatives thereof represents a valid strategy for regenerative purposes. Considering their paracrine/autocrine mode of actions that are able to regenerate injured tissues, trophic support, preventing apoptosis and fibrosis, promoting angiogenesis, stimulating the function and differentiation of endogenous stem cells and even reducing the immune response, are all important players in their future therapeutic success. Nevertheless, obtaining mesenchymal stromal cells (MSC) from adult tissues requires invasive procedures and implicates decreased cell proliferation and a reduced differentiation capacity with age. Alternatively, the use of embryonic stem cells as source of cellular therapeutic encountered several ethical concerns, as well as the risk of teratoma formation. Therefore, several studies have recently focussed on perinatal derivatives (PnD) that can be collected non-invasively and, most importantly, display similar characteristics in terms of regenerating-inducing properties, immune-modulating properties and hypo-immunogenicity. This review will provide an overview of the current knowledge and future perspectives of PnD application in the treatment of ovarian hypofunction.
Role of Canonical Wnt/β-Catenin Pathway in Regulating Chondrocytic Hypertrophy in Mesenchymal Stem Cell-Based Cartilage Tissue Engineering
Authors: Wang Xueqi , Guan Yiming , Xiang Shiyu , Clark Karen L. , Alexander Peter G. , Simonian Lauren E. , Deng Yuhao , Lin Hang 
Published: January 2022

In the past 3 decades, the cartilage repair potential of mesenchymal stromal cells, or mesenchymal stem cells (MSCs), has been widely examined in animal studies. Unfortunately, the phenotype and physical properties of MSC-derived cartilage tissue are not comparable to native hyaline cartilage. In particular, chondrocytic hypertrophy, a phenotype that is not observed in healthy hyaline cartilage, is concomitant with MSC chondrogenesis. Given that hypertrophic chondrocytes potentially undergo apoptosis or convert into osteoblasts, this undesired phenotype needs to be prevented or minimized before MSCs can be used to repair cartilage injuries in the clinic. In this review, we first provide an overview of chondrocytic hypertrophy and briefly summarize current methods for suppressing hypertrophy in MSC-derived cartilage. We then highlight recent progress on modulating the canonical Wnt/β-catenin pathway for inhibiting hypertrophy. Specially, we discuss the potential crosstalk between Wnt/β-catenin with other pathways in regulating hypertrophy. Lastly, we explore future perspectives to further understand the role of Wnt/β-catenin in chondrocytic hypertrophy.
Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma
Authors: Wu Min , Wei Bo , Duan Sai-Li , Liu Mian , Ou-Yang Deng-Jie , Huang Peng , Chang Shi 
Published: January 2022

Purpose: Aberrant DNA methylation plays a crucial role in the tumorigenesis of differentiated thyroid cancer (DTC); nevertheless, the factors leading to the local and regional recurrence of DTC are not well understood. This study aimed to establish the connection between DNA methylation-driven genes and the recurrence of DTC.Methods: RNA sequencing profiles and DNA methylation profiles of DTC were downloaded from The Cancer Genome Atlas (TCGA) database. Combined application of the methylmix R package and univariate Cox regression analyses were used to screen and distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses were utilized to identify the target genes that were closely associated with the recurrence of DTC. Then, correlations between the expression levels of the target genes and the clinicopathological features were verified, as well as their potential biological functions.Results: A total of 168 Methylation-driven genes were differentially expressed in thyroid cancer, among which 10 genes (GSTO2, GSTM5, GSTM1, GPX7, FGF2, LIF, PLAU, BCL10, SHARPIN and TNFRSF1A) were identified as Hub genes. We selected PLAU for further analysis because PLAU was most strongly correlated with DTC recurrence and the DNA methylation levels of PLAU were closely associated with multiple clinicopathological features of DTC. PLAU was significantly upregulated in DTC, and patients with a high expression level of PLAU had a higher risk of recurrence (p &lt; 0.05). Functional predictions suggested that PLAU-related genes were mainly involved in the regulation of immune-related signaling pathways. Moreover, the mRNA level of PLAU was found to be positively correlated with the cell markers of neutrophils and dendritic cells. In addition, we found that two DNA methylation sites (cg06829584, cg19399285) were associated with abnormal expression of PLAU in DTC.Conclusion: The methylation-driven gene PLAU is an independent risk factor for the recurrence of DTC and it functions as an oncogene through the regulation of immune-related signaling pathways, which offers new insight into the molecular mechanisms of thyroid cancer and provides new possibilities for individualized treatment of thyroid cancer patients.
Magnetic Field-Enhanced Agglutination Readout Combined With Isothermal Reverse Transcription Recombinase Polymerase Amplification for Rapid and Sensitive Molecular Detection of Dengue Virus
Authors: Leon Fanny , Pinchon Elena , Mayran Charly , Daynès Aurélien , Morvan François , Molès Jean-Pierre , Cantaloube Jean-François , Fournier-Wirth Chantal 
Published: January 2022

Among the numerous molecular diagnostic methods, isothermal reverse transcription recombinase polymerase amplification (RT-RPA) is a simple method that has high sensitivity and avoids the use of expensive instruments. However, detection of amplified genomes often requires a fluorescence readout on costly readers or migration on a lateral flow strip with a subjective visual reading. Aiming to establish a new approach to rapidly and sensitively detect viruses, we combined RT-RPA with a magnetic field-enhanced agglutination (MFEA) assay and assessed the ability of this method to detect the dengue virus (DENV). Magnetization cycles accelerated the capture of amplified DENV genomes between functionalized magnetic nanoparticles by a fast chaining process to less than 5 min; the agglutination was quantified by simple turbidimetry. A total of 37 DENV RNA+ and 30 DENV RNA− samples were evaluated with this combined method. The sensitivity and specificity were 89.19% (95% CI, 72.75–100.00%) and 100% (95% CI, 81.74–100.00%), respectively. This approach provides a solution for developing innovative diagnostic assays for the molecular detection of emerging infections.
Early Detection of Nucleation Events From Solution in LC-TEM by Machine Learning
Authors: Katsuno Hiroyasu , Kimura Yuki , Yamazaki Tomoya , Takigawa Ichigaku 
Published: January 2022

To support the detection, recording, and analysis of nucleation events during in situ observations, we developed an early detection system for nucleation events observed using a liquid-cell transmission electron microscope. Detectability was achieved using the machine learning equivalent of detection by humans watching a video numerous times. The detection system was applied to the nucleation of sodium chloride crystals from a saturated acetone solution of sodium chlorate. Nanoparticles with a radius of more greater than 150 nm were detected in a viewing area of 12 μm × 12 μm by the detection system. The analysis of the change in the size of the growing particles as a function of time suggested that the crystal phase of the particles with a radius smaller than 400 nm differed from that of the crystals larger than 400 nm. Moreover, the use of machine learning enabled the detection of numerous nanometer sized nuclei. The nucleation rate estimated from the machine-learning-based detection was of the same order as that estimated from the detection using manual procedures.
Antimicrobial Activity of a Repurposed Harmine-Derived Compound on Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates
Authors: Breine Anke , Van Gysel Mégane , Elsocht Mathias , Whiteway Clémence , Philippe Chantal , Quinet Théo , Valcek Adam , Wouters Johan , Ballet Steven , Van der Henst Charles 
Published: January 2022

ObjectivesThe spread of antibiotic resistant bacteria is an important threat for human health. Acinetobacter baumannii bacteria impose such a major issue, as multidrug- to pandrug-resistant strains have been isolated, rendering some infections untreatable. In this context, carbapenem-resistant A. baumannii bacteria were ranked as top priority by both WHO and CDC. In addition, A. baumannii bacteria survive in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is very challenging because of the requirement of drug target conservation amongst the different strains. Here, we screened a chemical library to identify compounds active against several reference strains and carbapenem-resistant A. baumannii bacteria.MethodsA repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining the IC50 and testing the activity on 43 modern clinical A. baumannii isolates, amongst which 40 are carbapenem-resistant.ResultsThe repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proves to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 µM. In addition, HDC1 impairs growth of 43 clinical A. baumannii isolates.ConclusionsWe identified a compound with inhibitory activity on all tested strains, including carbapenem-resistant clinical A. baumannii isolates.
Nocardia Infection in Nephrotic Syndrome Patients: Three Case Studies and A Systematic Literature Review
Authors: Cheng Yan , Wang Tian-yi , Yuan Hong-li , Li Wei , Shen Jing-ping , He Zheng-xin , Chen Jing , Gao Jie-ying , Wang Fu-kun , Gu Jiang 
Published: January 2022

ObjectiveThe multicenter literature review and case studies of 3 patients were undertaken to provide an updated understanding of nocardiosis, an opportunistic bacterial infection affecting immunosuppressed nephrotic syndrome (NS) patients receiving long-term glucocorticoid and immunosuppressant treatment. The results provided clinical and microbiological data to assist physicians in managing nocardiosis patients.MethodsThree cases between 2017 and 2018 from a single center were reported. Additionally, a systematic review of multicenter cases described in the NCBI PubMed, Web of Science, and Embase in English between January 1, 2001 and May 10, 2021 was conducted.ResultsThis study described three cases of Nocardia infection in NS patients. The systematic literature review identified 24 cases with sufficient individual patient data. A total of 27 cases extracted from the literature review showed that most patients were &gt; 50 years of age and 70.4% were male. Furthermore, the glucocorticoid or corticosteroid mean dose was 30.9 ± 13.7 mg per day. The average time between hormone therapy and Nocardia infection was 8.5 ± 9.7 months. Pulmonary (85.2%) and skin (44.4%) infections were the most common manifestations in NS patients, with disseminated infections in 77.8% of patients. Nodule/masses and consolidations were the major radiological manifestations. Most patients showed elevated inflammatory biomarkers levels, including white blood cell counts, neutrophils percentage, and C-reactive protein. Twenty-five patients received trimethoprim-sulfamethoxazole monotherapy (18.5%) or trimethoprim-sulfamethoxazole-based multidrug therapy (74.1%), and the remaining two patients (7.4%) received biapenem monotherapy. All patients, except the two who were lost to follow-up, survived without relapse after antibiotic therapy.ConclusionsNephrotic syndrome patients are at high risk of Nocardia infection even if receiving low-dose glucocorticoid during the maintenance therapy. The most common manifestations of nocardiosis in NS patients include abnormal lungs revealing nodules and consolidations, skin and subcutaneous abscesses. The NS patients have a high rate of disseminated and cutaneous infections but a low mortality rate. Accurate and prompt microbiological diagnosis is critical for early treatment, besides the combination of appropriate antibiotic therapy and surgical drainage when needed for an improved prognosis.
No-Touch Sequential Saphenous Venous Harvesting Technique in Off-Pump Bypass Surgery: A Retrospective Study
Authors: Hou Xuejian , Zhang Kui , Liu Taoshuai , Li Yang , Zhao Yang , Song Bangrong , Huang Zhuhui , Zheng Jubing , Dong Ran 
Published: January 2022

BackgroundIn the mid-1990s, the Swedish expert team proposed saphenous vein graft (SVG) harvesting with pedicle tissue. The short-term and long-term patency rates of the great saphenous vein obtained by the no-touch (NT) were higher than those obtained by the conventional (CON). In the past, NT harvesting was mainly used in on-pump coronary artery bypass grafting (CABG), and vein grafts were mostly single vein grafts. In this study, we retrospectively analyzed the safety and effectiveness of sequential vein grafts using NT harvesting in off-pump CABG.MethodsFrom 2017 to 2019, a total of 505 patients were included in the study. There were 150 patients in the NT group and 355 patients in the CON group. After applying propensity score matching (1:1 matching), 148 patients were included in each group. Baseline data, graft patency, post-operative complications, leg wound complications and 1-year major adverse cardiac and cerebrovascular events (MACCEs) were compared between the two groups.ResultsThere was no significant difference in the patency rate of sequential venous grafts between the two groups 1 year after the operation either before [NT: 7.1% (10/141) vs. CON: 11.5% (38/331), p = 0.149) or after matching (NT: 7.1% (10/140) vs. CON: 7.3% (9/124), p = 0.971]. There was no significant difference in the composite clinical endpoint between the two groups either before [NT: 3 (2.3%) vs. CON: 9 (2.8%), p = 1.000] or after matching [NT: 3 (2.3%) vs. CON: 3 (2.5%), p = 1.000]. There were differences in leg wound complications between the two groups both before [NT: 9 (6.9%) vs. CON: 6 (1.9%), p = 0.007] and after matching [NT: 9 (6.9%) vs. CON: 2 (1.7%), p = 0.043].ConclusionsThe application of the NT harvesting in off-pump CABG with sequential vein grafts is safe and effective. NT method has disadvantages in leg wound.
Risk Prediction Model for Uncontrolled Hypertension in Chinese Community
Authors: Gao Zhiping , Chen Shiqun , Huang Xiaoyu , Ye Jianfeng , Liu Jin , Huang Zhidong , Chen Jiyan , Li Liwen , Liu Yong , Lin Shuguang 
Published: January 2022

BackgroundUncontrolled hypertension rate was still high across China. This study develops and validates an index to help quantify the combination of socio-behavioral aspects to screen high-risk patients in uncontrolled hypertension in Chinese primary care.MethodsA cross-sectional study included 1,039 of patients with hypertension in the Chinese community. We assessed independent risk factors of uncontrolled blood pressure (defined as having a blood pressure ≥140/90 mmHg, even with antihypertensive therapy) and develop a risk prediction model.ResultsAmong the 1,039 patients (53.9% male, the average age was 61 ± 13 years), 452 (43.5%) were uncontrolled hypertensive. Multivariable analysis showed that worker (odds ratio, OR: 1.98, 95% CI: 1.46–2.69), no health insurance (OR: 3.47, 95% CI: 2.08–5.80), non-marital status (OR: 2.01, 95% CI: 1.35–3.27), and other socio-behavioral aspects were independent risk factors of uncontrolled hypertension, which were included the final prediction model (C-static: 0.781). With internal validation by the bootstrap method, the risk score showed good discriminating ability and predicting ability for the incidence of uncontrolled hypertension (C-static: 0.771).ConclusionsThis study showed that nearly half of the patients suffered from uncontrolled hypertension in the Chinese community. We established a prediction model with good predictability to help quantify the combination of socio-behavioral aspects and screen high-risk patients with uncontrolled hypertension.
Influence of the Duration of Tectonic Evolution on Organic Matter Pore Structure and Gas Enrichment in Marine Shale: A Case Study of the Lower Silurian Longmaxi Shale in Southern China
Authors: Li Xin , Wang Pengfei , Wang Shuai , Jin Can , Zhang Chen , Zhao Rui , Jiang Zhenxue 
Published: January 2022

The exploration and development of the shale in the Lower Silurian Longmaxi Formation in the Chongqing area has shown that gas production here is commercially viable. In contrast, the Longmaxi Formation shale in Hunan shows that gas production is not commercial. Why is there such a difference between the Chongqing and Hunan areas for the same formation. A mount of previous studies showed that gas is stored primarily in the organic matter (OM) pores in shale. This study has investigated the Longmaxi shale from two well locations in Chongqing and Hunan in order to understand whether differences in pore structure are the cause of the difference in commerciality in the two areas. The formation burial histories were established, analyzing samples for mineral composition, total organic carbon (TOC) content, thermal maturity (Ro), and OM pore structures. The results show that the Longmaxi shale in Chongqing and Hunan has similar TOC content and Ro. The average TOC content is above 3.0% for samples from both areas, and the thermal maturity was all between 2.4 and 2.9%. OM pores of the Longmaxi shale in Chongqing are abundant in number and relatively large sized, with mostly circular and oval shapes. In contrast, the number and size of the OM pores in the Longmaxi shale in Hunan are small, and the shape is irregular. OM pore structure of the Longmaxi shale in Chongqing is therefore favorable for preservation of gas. The poor pore structure of the Longmaxi shale in Hunan is not conducive to gas preservation. The OM pore structure difference of the Longmaxi shale in Chongqing and Hunan is determined by the formation burial history. The Longmaxi shale in the Chongqing area experienced rapid burial in the Early Jurassic and rapid uplift in the Late Cretaceous. The Longmaxi Formation in Hunan experienced rapid burial in the Early Triassic and rapid uplift in the Early Jurassic. The long evolution time (100 Ma) of the Longmaxi shale in Chongqing produced a large amount of gas supply and enough storage space (OM pores) for the gas occurrence, which makes the amount of gas be preserved in geological history. The short evolution time (50 Ma) of the Longmaxi shale in Hunan produced insufficient gas supply and not enough OM pores in reservoir, which leads to gas loss in geological history, resulting in low gas content. Therefore, to evaluate the potential of shale gas, the evolution time of organic matter must be considered. In other words, the time interval between rapid subsidence and uplift of formation during geological history must be considered.
Identification of Key LncRNAs and Pathways in Prediabetes and Type 2 Diabetes Mellitus for Hypertriglyceridemia Patients Based on Weighted Gene Co-Expression Network Analysis
Authors: Yan Shoumeng , Sun Mengzi , Gao Lichao , Yao Nan , Feng Tianyu , Yang Yixue , Li Xiaotong , Hu Wenyu , Cui Weiwei , Li Bo 
Published: January 2022

AimsPrevalence of prediabetes and type 2 diabetes mellitus(T2DM) are increasing worldwide. Key lncRNAs were detected to provide a reference for searching potential biomarkers of prediabetes and T2DM in hypertriglyceridemia patients.MethodsThe study included 18 hypertriglyceridemia patients: 6 newly diagnosed type 2 diabetes patients, 6 samples with prediabetes and 6 samples with normal blood glucose. Weighted gene co-expression network analysis (WGCNA) was conducted to construct co‐expression network and obtain modules related to blood glucose, thus detecting key lncRNAs.ResultsThe green, yellow and yellow module was significantly related to blood glucose in T2DM versus normal controls, T2DM versus prediabetes, prediabetes versus normal controls, respectively. ENST00000503273, ENST00000462720, ENST00000480633 and ENST00000485392 were detected as key lncRNAs for the above three groups, respectively.ConclusionsFor hypertriglyceridemia patients with different blood glucose levels, ENST00000503273, ENST00000462720 and ENST00000480633 could be potential biomarkers of T2DM.