bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of serum amyloid A1 in the adipogenic differentiation of human adipose-derived stem cells basing on single-cell RNA sequencing analysis
Authors: Qu Rongmei , He Kai , Yang Yuchao , Fan Tingyu , Sun Bing , Khan Asmat Ullah , Huang Wenhua , Ouyang Jun , Pan Xinghua , Dai Jingxing 
Published: May 2022

Abstract
Background
Adipose-derived stem cells (ASCs) are obtained from a variety of sources in vivo where they present in large quantities. These cells are suitable for use in autologous transplantation and the construction of tissue-engineered adipose tissue. Studies have shown that ASCs differentiation is in a high degree of heterogeneity, yet the molecular basis including key regulators of differentiation remains to clarify.

Methods
We performed single-cell RNA sequencing and bioinformatics analysis on both undifferentiated (ASC-GM group) and adipogenically differentiated human ASCs (ASC-AD group, ASCs were cultured in adipogenic inducing medium for 1 week). And then, we verified the results of serum amyloid A1 (SAA1) with western blotting, immunofluorescence staining, oil red O staining. After these experiments, we down-regulated the expression of serum amyloid A1 (SAA1) gene to verify the adipogenic differentiation ability of ASCs.

Results
In single-cell RNA sequence analyzing, we obtained 4415 cells in the ASC-GM group and 4634 cells in the ASC-AD group. The integrated sample cells could be divided into 11 subgroups (0–10 cluster). The cells in cluster 0, 2, 5 were came from ASC-GM group and the cells in cluster 1, 3, 7 came from ASC-AD group. The cells of cluster 4 and 6 came from both ASC-GM and ASC-AD groups. Fatty acid binding protein 4, fatty acid binding protein 5, complement factor D, fatty acid desaturase 1, and insulin like growth factor binding protein 5 were high expressed in category 1 and 7. Regulation of inflammatory response is the rank 1 biological processes. And cellular responses to external stimuli, negative regulation of defense response and acute inflammatory response are included in top 20 biological processes. Based on the MCODE results, we found that SAA1, C-C Motif Chemokine Ligand 5 (CCL5), and Annexin A1 (ANXA1) significantly highly expressed during adipogenic differentiation. Western blot and immunofluorescent staining results showed that SAA1 increased during adipogenesis. And the area of ORO positive staining in siSAA1 cells was significantly lower than in the siControl (negative control) cells.

Conclusions
Our results also indicated that our adipogenic induction was successful, and there was great heterogeneity in the adipogenic differentiation of ASCs. SAA1 with the regulation of inflammatory response were involved in adipogenesis of ASCs based on single-cell RNA sequencing analysis. The data obtained will help to elucidate the intrinsic mechanism of heterogeneity in the differentiation process of stem cells, thus, guiding the regulation of self-renewal and differentiation of adult stem cells.
Sex differences in the association between cardiovascular diseases and dementia subtypes: a prospective analysis of 464,616 UK Biobank participants
Authors: Dong Caiyun , Zhou Chunmiao , Fu Chunying , Hao Wenting , Ozaki Akihiko , Shrestha Nipun , Virani Salim S. , Mishra Shiva Raj , Zhu Dongshan 
Published: May 2022

Abstract
Background
Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown.

Methods
We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), lifestyle (smoking, BMI, leisure activities, and physical activity), genetic factors (APOE allele status), and medical history were also analyzed.

Results
Compared to people who did not experience a CVD event, the HRs (95%CI) between CVD and all-cause dementia were higher in women compared to men, with an RHR (Female/Male) of 1.20 (1.13, 1.28). Specifically, the HRs for AD were higher in women with CHD and heart failure compared to men, with an RHR (95%CI) of 1.63 (1.39, 1.91) and 1.32 (1.07, 1.62) respectively. The HRs for VD were higher in men with heart failure than women, with RHR (95%CI) of 0.73 (0.57, 0.93). An interaction effect was observed between socioeconomic, lifestyle, genetic factors, and medical history in the sex-specific association between CVD and dementia.

Conclusion
Women with CVD were 1.5 times more likely to experience AD than men, while had 15% lower risk of having VD than men.
Off-targetP ML: an open source machine learning framework for off-target panel safety assessment of small molecules
Authors: Naga Doha , Muster Wolfgang , Musvasva Eunice , Ecker Gerhard F. 
Published: May 2022

AbstractUnpredicted drug safety issues constitute the majority of failures in the pharmaceutical industry according to several studies. Some of these preclinical safety issues could be attributed to the non-selective binding of compounds to targets other than their intended therapeutic target, causing undesired adverse events. Consequently, pharmaceutical companies routinely run in-vitro safety screens to detect off-target activities prior to preclinical and clinical studies. Hereby we present an open source machine learning framework aiming at the prediction of our in-house 50 off-target panel activities for ~ 4000 compounds, directly from their structure. This framework is intended to guide chemists in the drug design process prior to synthesis and to accelerate drug discovery. We also present a set of ML approaches that require minimum programming experience for deployment. The workflow incorporates different ML approaches such as deep learning and automated machine learning. It also accommodates popular issues faced in bioactivity predictions, as data imbalance, inter-target duplicated measurements and duplicated public compound identifiers. Throughout the workflow development, we explore and compare the capability of Neural Networks and AutoML in constructing prediction models for fifty off-targets of different protein classes, different dataset sizes, and high-class imbalance. Outcomes from different methods are compared in terms of efficiency and efficacy. The most important challenges and factors impacting model construction and performance in addition to suggestions on how to overcome such challenges are also discussed.
Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images
Authors: Halme Hanna-Leena , Ihalainen Toni , Suomalainen Olli , Loimaala Antti , Mätzke Sorjo , Uusitalo Valtteri , Sipilä Outi , Hippeläinen Eero 
Published: May 2022

Abstract
Background
Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0–3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models.

Results
Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features.

Conclusion
Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.
Localization of TSH-secreting pituitary adenoma using 11C-methionine image subtraction
Authors: Gillett Daniel , Senanayake Russell , MacFarlane James , van der Meulen Merel , Koulouri Olympia , Powlson Andrew S. , Crawford Rosy , Gillett Bethany , Bird Nick , Heard Sarah , Kolias Angelos , Mannion Richard , Aloj Luigi , Mendichovszky Iosif A. , Cheow Heok , Bashari Waiel A. , Gurnell Mark 
Published: May 2022

Abstract
Background
Pituitary adenomas (PA) affect ~ 1:1200 of the population and can cause a wide range of symptoms due to hormone over-secretion, loss of normal pituitary gland function and/or compression of visual pathways, resulting in significantly impaired quality of life. Surgery is potentially curative if the location of the adenoma can be determined. However, standard structural (anatomical) imaging, in the form of MRI, is unable to locate all tumors, especially microadenomas (< 1 cm diameter). In such cases, functional imaging [11C-methionine PET/CT (Met-PET)] can facilitate tumor detection, although may be inconclusive when the adenoma is less metabolically active. We, therefore, explored whether subtraction imaging, comparing findings between two Met-PET scans with medical therapy-induced suppression of tumor activity in the intervening period, could increase confidence in adenoma localization. In addition, we assessed whether normalization to a reference region improved consistency of pituitary gland signal in healthy volunteers who underwent two Met-PET scans without medical suppression.

Results
We found that the mean percentage differences in maximum pituitary uptake between two Met-PET scans in healthy volunteers were 2.4% for (SUVr) [cerebellum], 8.8% for SUVr [pons], 5.2% for SUVr [gray matter] and 23.1% for the SUVbw [no region]. Laterality, as measured by contrast–noise ratio (CNR), indicated the correct location of the adenoma in all three image types with mean CNR values of 6.2, 8.1 and 11.1 for SUVbw, SUVbwSub and SUVrSub [cerebellum], respectively. Subtraction imaging improved CNR in 60% and 100% of patients when using images generated from SUVbw [no region] and SUVr [cerebellum] scans compared to standard clinical SUVbw imaging.

Conclusions
Met-PET scans should be normalized to the cerebellum to minimize the effects of physiological variation in pituitary gland uptake of 11C-methionine, especially when comparing serial imaging. Subtraction imaging following endocrine suppression of tumor function improved lateralization of PA when compared with single time point clinical Met-PET but, importantly, only if the images were normalized to the cerebellum prior to subtraction.
Herbicidal secondary metabolites from Bacillus velezensis JTB8-2 against Orobanche aegyptiaca
Authors: He Wei , Li Yan , Luo Wenfang , Zhou Junhui , Zhao Sifeng , Xu Jianjun 
Published: May 2022

AbstractEgyptian broomrape (Orobanche aegyptiaca) is a parasitic plants that cause significant losses to important crops. The effective methods for controlling this weed are rare. Biological control could be one of the possible strategies to tackle these weeds efficiently. In this work, a bacteria strain Bacillus velezensis JTB8–2 was proven to possesse biological control functions against broomrapes in both pot and field experiments. Four secondary metabolites (1–4) were isolated from the B. velezensis JTB8–2 crude extracts, and all of them could inhibit the germination of O. aegyptiaca seeds at concentrations from 0.5 mM to 4 mM. Their structures were further elucidated by Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) analysis. Among the isolated compounds, 1 and 2 exhibited the strongest herbicidal activity with 100% inhibition rate against the germination of O. aegyptiaca seeds at 4 mM, and thus had great potential in the development of new herbicidal products to control O. aegyptiaca in the future.
PA2G4 promotes the metastasis of hepatocellular carcinoma by stabilizing FYN mRNA in a YTHDF2-dependent manner
Authors: Sun Sheng , Liu Yiyang , Zhou Meiling , Wen Jinyuan , Xue Lin , Han Shenqi , Liang Junnan , Wang Yufei , Wei Yi , Yu Jinjin , Long Xin , Chen Xiaoping , Liang Huifang , Huang Zhao , Zhang Bixiang 
Published: May 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality. Advanced stage upon diagnosis and cancer metastasis are the main reasons for the dismal prognosis of HCC in large part. The role of proliferation associated protein 2G4 (PA2G4) in tumorigenesis and cancer progression has been widely investigated in various cancers. However, whether and how PA2G4 participates in HCC metastasis is still underexplored.

Results
We found that the mRNA and protein levels of PA2G4 were higher in HCC samples than in normal liver tissues, and high expression of PA2G4 in HCC was correlated with a poor prognosis, by an integrative analysis of immunohistochemistry (IHC), western blot and bioinformatic approach. Moreover, the expression of PA2G4 was elevated in HCC patients with metastases than those metastasis-free. Cell migration, invasion, phalloidin staining and western blot analyses demonstrated that PA2G4 promoted epithelial to mesenchymal transition (EMT) of HCC cells in vitro. And a lung metastasis animal model exhibited that PA2G4 enhanced metastatic ability of HCC cells in vivo. RNA-sequencing combined with dual luciferase reporter assay and evaluation of mRNA half-time indicated that PA2G4 increased FYN expression by stabilizing its mRNA transcript. Recovering the impaired FYN level induced by PA2G4 knockdown rescued the impeded cell mobilities. Furthermore, endogenous immunoprecipitation (IP) and in-situ immunofluorescence (IF) showed that YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) was the endogenous binding patterner of PA2G4. In addition, RNA binding protein immunoprecipitation (RIP) and anti- N6-methyladenosine immunoprecipitation (MeRIP) assays demonstrated that FYN mRNA was N6-methyladenosine (m6A) modified and bound with PA2G4, as well as YTHDF2. Moreover, the m6A catalytic ability of YTHDF2 was found indispensable for the regulation of FYN by PA2G4. At last, the correlation of expression levels between PA2G4 and FYN in HCC tissues was verified by IHC and western blot analysis.

Conclusions
These results indicate that PA2G4 plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 may become a reliable prognostic marker or therapeutic target for HCC patients.
AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology
Authors: Tsimberidou Apostolia-Maria , Skliris Antonis , Valentine Alan , Shaw Jamie , Hering Ursula , Vo Henry Hiep , Chan Tung On , Armen Roger S. , Cottrell Jeffrey R. , Pan Jen Q. , Tsichlis Philip N. 
Published: May 2022

Abstract
Background
Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods
(1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms (SNPs) in the AKT3 gene. (3) We analyzed the psychiatric adverse events (AEs) of patients treated with M2698 (p70S6K/AKT1/AKT3 inhibitor) and with other PI3K/AKT/mTOR pathway inhibitors.

Results
(1) Proteins encoded by AKT3 (AKT3Q60H) and AKT1 (AKT1Q61H) mutants had lower kinase activity than those encoded by wild-type AKT3 and AKT1, respectively. Molecular modeling of the AKT1-Q61H mutant suggested conformational changes that may reduce the binding of D3-phosphorylated phosphoinositides to the PH domain. (2) We identified multiple SNPs in the AKT3 gene that were strongly associated with schizophrenia (p < 0.5 × 10–8). (3) Psychiatric AEs, mostly insomnia, anxiety, and depression, were noted in 29% of patients treated with M2698. In randomized studies, their incidence was higher in PI3K/AKT/mTOR inhibitor arms compared with placebo arms. All psychiatric AEs were reversible.

Conclusions
Our data elucidate the incidence and mechanisms of psychiatric AEs in patients treated with PI3K/AKT/mTOR inhibitors and emphasize the need for careful monitoring.
Single-cell genomics identifies distinct B1 cell developmental pathways and reveals aging-related changes in the B-cell receptor repertoire
Authors: Luo Yao , Wang Jing , Li Kairui , Li Mingxia , Xu Shasha , Liu Xingjie , Zhang Zhiwei , Xu Xiang , Zhang Yu , Pan Jiawei , Liu Pengtao , Gao Shaorong , Miao Zhichao , Yu Yong 
Published: May 2022

AbstractBackgroundB1 cells are self-renewing innate-like B lymphocytes that provide the first line of defense against pathogens. B1 cells primarily reside in the peritoneal cavity and are known to originate from various fetal tissues, yet their developmental pathways and the mechanisms underlying maintenance of B1 cells throughout adulthood remain unclear.ResultsWe performed high-throughput single-cell analysis of the transcriptomes and B-cell receptor repertoires of peritoneal B cells of neonates, young adults, and elderly mice. Gene expression analysis of 31,718 peritoneal B cells showed that the neonate peritoneal cavity contained many B1 progenitors, and neonate B cell specific clustering revealed two trajectories of peritoneal B1 cell development, including pre-BCR dependent and pre-BCR independent pathways. We also detected profound age-related changes in B1 cell transcriptomes: clear difference in senescence genetic program was evident in differentially aged B1 cells, and we found an example that a B1 subset only present in the oldest mice was marked by expression of the fatty-acid receptor CD36. We also performed antibody gene sequencing of 15,967 peritoneal B cells from the three age groups and discovered that B1 cell aging was associated with clonal expansion and two B1 cell clones expanded in the aged mice had the same CDR-H3 sequence (AGDYDGYWYFDV) as a pathogenically linked cell type from a recent study of an atherosclerosis mouse model.ConclusionsBeyond offering an unprecedent data resource to explore the cell-to-cell variation in B cells, our study has revealed that B1 precursor subsets are present in the neonate peritoneal cavity and dissected the developmental pathway of the precursor cells. Besides, this study has found the expression of CD36 on the B1 cells in the aged mice. And the single-cell B-cell receptor sequencing reveals B1 cell aging is associated with clonal expansion.
Association of immediate reinsertion of new catheters with subsequent mortality among patients with suspected catheter infection: a cohort study
Authors: Zhong Yiyue , Deng Liehua , Zhou Limin , Liao Shaoling , Yue Liqun , Wen Shi Wu , Xie Rihua , Lu Yuezhen , Zhang Liangqing , Tang Jing , Wu Jiayuan 
Published: May 2022

Abstract
Background
Central venous catheter (CVC) insertion complications are a prevalent and important problem in the intensive care unit (ICU), and source control by immediate catheter removal is considered urgent in patients with septic shock suspected to be caused by catheter-related bloodstream infection (CRBSI). We sought to determine the impact of immediate reinsertion of a new catheter (IRINC) on mortality among patients after CVC removal for suspected CRBSI.

Methods
A propensity score-matched cohort of patients with suspected CRBSI who underwent IRINC or no IRINC in a 32-bed ICU in a university hospital in China from January 2009 through April 2021. Catheter tip culture and clinical symptoms were used to identify patients with suspected CRBSI. The Kaplan–Meier method was used to analyse 30-day mortality before and after propensity score matching, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality in the matched cohort were estimated with Cox proportional hazards models.

Results
In total, 1,238 patients who had a CVC removed due to suspected CRBSI were identified. Among these patients, 877 (70.8%) underwent IRINC, and 361 (29.2%) did not. Among 682 propensity score-matched patients, IRINC was associated with an increased risk of 30-day mortality (HR, 1.481; 95% CI, 1.028 to 2.134) after multivariable, multilevel adjustment. Kaplan–Meier analysis found that IRINC was associated with the risk of mortality both before matching (P = 0.00096) and after matching (P = 0.018). A competing risk analysis confirmed the results of the propensity score-matched analysis. The attributable risk associated with bloodstream infection was not significantly different (HR, 1.081; 95% CI 0.964 to 1.213) among patients with suspected CRBSI in terms of 30-day mortality compared with that associated with other infections.

Conclusions
In this cohort study, IRINC was associated with higher 30-day mortality compared to delayed CVC or no CVC among patients with suspected CRBSI. A large-sample randomized controlled trial is needed to define the best management for CVC in cases of suspected CRBSI because IRINC may also be associated with noninfectious complications.
Trial registration This study was registered with the China Clinical Trials Registry (URL: http://www.chictr.org.cn/index.aspx) under the following registration number: ChiCTR1900022175.
Intrusion detection system combined enhanced random forest with SMOTE algorithm
Authors: Wu Tao , Fan Honghui , Zhu Hongjin , You Congzhe , Zhou Hongyan , Huang Xianzhen 
Published: May 2022

AbstractNetwork security is subject to malicious attacks from multiple sources, and intrusion detection systems play a key role in maintaining network security. During the training of intrusion detection models, the detection results generally have relatively large false detection rates due to the shortage of training data caused by data imbalance. To address the existing sample imbalance problem, this paper proposes a network intrusion detection algorithm based on the enhanced random forest and synthetic minority oversampling technique (SMOTE) algorithm. First, the method used a hybrid algorithm combining the K-means clustering algorithm with the SMOTE sampling algorithm to increase the number of minor samples and thus achieved a balanced dataset, by which the sample features of minor samples could be learned more effectively. Second, preliminary prediction results were obtained by using enhanced random forest, and then the similarity matrix of network attacks was used to correct the prediction results of voting processing by analyzing the type of network attacks. In this paper, the performance was tested using the NSL-KDD dataset with a classification accuracy of 99.72% on the training set and 78.47% on the test set. Compared with other related papers, our method has some improvement in the classification accuracy of detection.