bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised Spammer Detection in Social Networks based on User Information Interests
Authors: Koggalahewa Darshika , Xu Yue , Foo Ernest 
Published: August 2021

Abstract
Online Social Networks (OSNs) are a popular platform for communication and collaboration. Spammers are highly active in OSNs. Uncovering spammers has become one of the most challenging problems in OSNs. Classification-based supervised approaches are the most commonly used method for detecting spammers. The classification-based systems suffer from limitations of “data labelling”, “spam drift”, “imbalanced datasets” and “data fabrication”. These limitations effect the accuracy of a classifier’s detection. We present a pure unsupervised approach for spammer detection based on peer acceptance of a user in a social network to distinguish spammers from genuine users. The peer acceptance of a user to another user is calculated based on common shared interests over multiple shared topics between the two users. The main contribution of this paper is the introduction of a pure unsupervised spammer detection approach based on users’ peer acceptance. Our approach does not require labelled training datasets. While it does not better the accuracy of supervised classification-based approaches, our approach has become a successful alternative for traditional classifiers for spam detection by achieving an accuracy of 96.9%.
The Autism Risk Factor CHD8 Is a Chromatin Activator in Human Neurons and Functionally Dependent on the ERK-MAPK Pathway Effector ELK1
Authors: Derafshi Bahareh Haddad , Danko Tamas , Chanda Soham , Batista Pedro , Litzenburger Ulrike , Lee Qian Yi , Ng Yi Han , Sebin Anu , Chang Howard Y. , Südhof Thomas C. , Wernig Marius 
Published: August 2021

Abstract
The chromodomain helicase DNA-binding protein CHD8 is among the most frequently found de-novo mutations in autism spectrum disorder (ASD)1-4. Despite its prominent disease involvement, little is known about its molecular function in the human brain. CHD8 is believed to be a chromatin regulator, but mechanisms for its genomic targeting is also unclear. To elucidate the role of CHD8 in human neurons, we generated conditional loss-of-function alleles in pluripotent stem cells. Chromatin accessibility and transcriptional profiling showed that CHD8 is a potent chromatin opener and transcriptional activator of its direct neuronal targets, including a distinct group of ASD genes. We found the chromatin targeting of CHD8 to be highly context dependent. In human neurons, CHD8 was preferentially bound at promoter sequences which were significantly enriched in ETS motifs. Indeed, the chromatin state of ETS motif-containing promoters was preferentially affected upon loss of CHD8. Among the many ETS transcription factors, we found ELK1 to be the best correlated with CHD8 expression in primary human fetal and adult cortical neurons and most highly expressed in our ES cell-derived neurons. Remarkably, ELK1 was necessary to recruit CHD8 specifically to ETS motif-containing sites. These findings imply the functional cooperativity between ELK1, a key downstream factor of the MAPK/ERK pathway, and CHD8 on chromatin involvement in human neurons. THEREFORE, the MAPK/ERK/ELK1 axis may also play a role in the pathogenesis caused by CHD8 mutations5 .
Genome Analysis of The Salt-Resistant Paludifilum Halophilum DSM 102817T Reveals Genes Involved In Flux-Tuning of Ectoines And Unexplored Bioactive Secondary Metabolites
Authors: Frikha-Dammak Donyez , Ayadi Houda , Rekik Imen Hakim , Belbahri Lassaad , Maalej Sami 
Published: August 2021

Abstract
Paludifilum halophilum is the first member of the genus Paludifilum in the Thermoactinomycetaceae family. The thermohalophilic bacterium was isoated from the solar saltern of Sfax, in Tunisia and was shown to be able to produce ectoines in relatively high-yield and cope with salt stress conditions. In this study, the whole genome of P. halophilum was sequenced and analysed. Analysis revealed 3,789,765 base pairs with average GC % content of 51.5%. A total of 3,775 genes were predicted of which 3616 were protein-coding genes and 73 were RNA genes. The genes encoding key enzymes for ectoines synthesis were identified from the bacterial genome next to a gene cluster (ehuABCD) encoding a binding-protein-dependent ABC transport system responsible for ectoines mobility through the cell membrane. With the aid of KEGG analysis, we found that the central catabolic network of P. halophilum comprises the pathways of glycolysis, tricarboxylic acid (TCA) cycle, and pentose phosphate pathway (PPP). In addition, anaplerotic pathways replenishing oxaloacetate and glutamate synthesis from central metabolism, both needed for high ectoines biosynthetic fluxes were identified through several key enzymes. Furthermore, a total of 18 antiSMASH-predicted putative biosynthetic gene clusters (BGCs) for secondary metabolites with high novelty and diversity were identified in P. halophilum genome, including biosynthesis of Colabomycine-A, Fusaricidin-E, Zwittermycin A, Streptomycin, Mycosubtilin and Meilingmycin. Based on these data, P. halophilum emerged as a promising source for ectoines and antimicrobials with the potential to be scaled up for industrial production, which could benefit the pharmaceutical and cosmetic industries.
Dynamic regulation of mitochondrial pyruvate metabolism Is necessary for orthotopic pancreatic tumor growth
Authors: Ruiz Nancy P Echeverri , Mohan Vijay , Wu Jinghai , Scott Sabina , Kreamer McKenzie , Benej Martin , Papandreou Ioanna , Denko Nicholas 
Published: August 2021

Abstract
BackgroundPyruvate dehydrogenase complex (PDC) plays a central role in carbohydrate metabolism, linking cytoplasmic glycolysis to the mitochondrial tricarboxylic acid (TCA) cycle. PDC is a conserved E1-E2-E3 dehydrogenase with a PDHA1 and PDHB heterotetramer functioning as the E1 subunit. PDHA1 contains three serine residues that can be reversibly phosphorylated by a dedicated family of four inhibitory pyruvate dehydrogenase kinases (PDHK1-4) and two reactivating phosphatases (PDP1,2). Hypoxia induces the expression of PDHK1 and PDHK3 and hyperphosphorylates PDHA1. The role of PDC in metabolic reprogramming and tumor progression appears to be for the integration of oncogenic and environmental signals which supports tumor growth. MethodsTo isolate the function of the serine-dependent regulation pf PDC, we engineered MiaPaca2 cells to express PDHA1 protein with either intact serines at positions 232, 293 and 300, or all the combinations of non-phosphorylatable alanine substitution mutations. These lines were compared in vitro for biochemical response to hypoxia by western blot, metabolic activity by biochemical assay and Seahorse XF flux analysis, and growth in media with reduced exogenous metabolites. The lines were also tested for growth in vivo after orthotopic injection into the pancreata of immune-deficient mice. ResultsIn this family of cells with non-phosphorylatable PDHA1 we found reduced hypoxic phosphorylation of PDHA1, decreased PDH enzymatic activity in normoxia and hypoxia, decreased mitochondrial function by Seahorse flux assay, reduced in vitro growth of cells in media depleted of lipids, and reduced growth of tumors after orthotopic transplantation of cells into the pancreata of immune-deficient mice. ConclusionsWe found that any substitution of alanine for serine at regulatory sites generated a hypomorphic PDC. However, the reduced PDC activity was insensitive to further reduction in hypoxia. These cells had very modest reduction of growth in vitro, but were significantly compromised in their growth as tumors, indicating that dynamic PDC adaptation to microenvironmental conditions is necessary for optimal pancreatic cancer growth in vivo.
Ginseng Polysaccharides and its Effective Subfraction Protects Against Dextran Sodium Sulfate-Induced Colitis via Regulating NF-κB Signaling Pathway, Recovering Intestinal Barrier and Adjusting Gut Microbiota
Authors: Li Shanshan , Qi Yuli , Ren Duoduo , Zhang Yue , Sun Yinshi 
Published: August 2021

Abstract
Background: Polysaccharides from Panax ginseng is a natural carbohydrates with multiple activities. Our previous work found that ginseng polysaccharide could recover the gut microbiota dysbiosis caused by antibiotic. However, it was little known about its functions on colitis. In this study, we aim to investigate the protective effects of ginseng polysaccharide (WGP), its neutral fraction (WGPN) and acidic fraction (WGPA) on dextran sodium sulfate (DSS) induced colitis and the potential mechanisms with pharmacological experiments.Methods: Animal model of DSS-induced colitis was constructed by male Wistar rats. Disease activity index (DAI) scores, weight increment, colon weights, and colon length were recorded. Physiological and histological parameters, tight junctions proteins, inflammatory factors, gut microbiota, short-chain fatty acids (SCFAs) and NF-kB signalling pathway related proteins were compared among the five experimental groups, which were treated with a normal diet (Con group), DSS (DSS group), WGP (WGP group), WGPN (WGPN group), and WGPA (WGPA group), respectively. Results: Both WGP and WGPA alleviated the colitis symptoms and colon structure changes of colitis rats. They can decreased the DAIs and improved colon health; reduced colon damage and recovered intestinal barrier via regulating the tight-junction related proteins (ZO-1 and Occludin); downregulated inflammatory cytokines (IL-1β, IL-2, IL-6, and IL-17) and inhibited the TLR4/MyD88/NF-kB signalling pathway in the colon; regulated the diversity and composition of gut microbiota, especially the relative abundance of Ruminococcus; enhanced the production of SCFAs. Conclusions: WGP exerted had a protective effect against colitis through regulating NF-kB signaling pathway, recovering intestinal barrier and adjusting gut microbiota, with its acidic fraction (WGPA) primarily contributing to this activity. The results support to the utilization and investigation of ginseng polysaccharides as potential intervention strategy for the prevention of colitis.
Combining Blood Glucose and SpO 2 /FiO 2 Ratio Facilitates Prediction of Imminent Ventilatory Needs in Emergency Room COVID-19 patients
Authors: Sakai Kazuya , Okoda Kai , Nishii Mototsugu , Saji Ryo , Ogawa Fumihiro , Abe Takeru , Takeuchi Ichiro 
Published: August 2021

Abstract
The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 hours (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, the combination of SpO2/FiO2 ratio and BG, which can be measured easily and immediately, showed higher accuracy in its prediction (AUC: 0.88) compared to SpO2/FiO2 ratio alone (AUC: 0.84). Moreover, even in patients without severe respiratory failure (SpO2/FiO2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO2/FiO2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV.
GD2-specific Chimeric Antigen Receptor-modified T Cells for the treatment of Refractory and/or Recurrent Neuroblastoma in Pediatric Patients
Authors: Yu Lihua , Huang Lulu , Lin Danna , Lai Xiaorong , Wu Li , Liao Xu , Liu Jiale , Zeng Yinghua , Liang Lichan , Zhang Guanmei , Wang Bin , Wu Zhu , Tao Shaohua , Liu Yuchen , Jiao Cheng , Chang Lung-Ji , Yang Lihua 
Published: August 2021

Abstract
PurposeThis study aimed to evaluate the safety and efficacy of the fourth-generation chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. Experimental DesignA phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB /CD3ζ-iCasp9 was transduced into activated T-cells. The response to 4SCAR-GD2 T cell treatment, and 4SCARGD2 T cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. ResultsTwelve patients were enrolled and finally ten ptients were included in this clinical trial which occurred from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T cell infusion. After 4SCAR-GD2 T cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4(4/10) remained SD at 1 year and alive after 3-4 years of follow up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00 to 59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25 to 15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1-2 toxicities like cytokine release syndrome and neuropathic pain were common, transient and mild. ConclusionsThe 4SCAR-GD2 T cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.
Purification and Characterization of Polyphenol Oxidase Enzyme from Damson Plum (Prunus insititia) by Spectrophotometrically
Authors: Yıldız Selinnur , Bilen Çiğdem , Karakuş Emine 
Published: August 2021

Abstract
Polyphenol oxidase enzyme, performing browning reactions in fruits and vegetables, was purificated from damson plum (Prunus insititia) which has a high antioxidant activity. Firstly, partially purified polyphenol oxidase was treated by 0-80% ammonium sulfate precipitation and dialysis, respectively. Characterization studies were carried out by using catechol, 4-methyl catechol, pyrogallol and caffeic acid as 0.05M/ pH:7.2/ 25°C; 0.2M/ pH:4.5/ 10°C; 0.01M/ pH:6.8/ 5°C and 0.2M/ pH:8.5/ 10°C, respectively. The kinetic constants of Vmax and KM were calculated for the same substrates as 17219.97 U/(mL*min) and 11.67mM; 7309.72 U/(mL*min) and 5mM; 12580.12 U/(mL*min) and 3.74mM; 12100.41 U/(mL*min) and 6.25 mM, respectively. Catechol gave the highest Vmax value when compared to others. In the second step, purification was performed by using Sepharose 4B-L-Tyrosine-p-amino benzoic acid and Sepharose 6B-L-Tyrosine-p-amino benzoic acid affinity gels. A single band of approximately as 50-55 kDa was observed in SDS-PAGE and Native-PAGE. 90 and 10.2 purification folds were obtained for Prunus insititia PPO by the reference Sepharose-4B-L-Tyrosine-p-aminobenzoic acid and original Sepharose-6B-L-Tyrosine-p-aminobenzoic acid gels, respectively. PPO enzyme purification from Prunus insititia by affinity chromatography has not been investigated in literature yet.
Identify Factors for Insufficient (&gt;2yr) Mammogram Screening among Oregonian Women
Authors: Zhang Zhenzhen , Curran Grace , Xu Kenneth , Lim Jeong Youn , Farris Paige E , Shannon Jackilen 
Published: August 2021

Abstract
Purpose: Women with breast cancer diagnosed from mammogram screenings have a lower mortality risk than women diagnosed from symptoms. Currently, the U.S Preventive Services Task Force recommends biannual screening for women aged 50-74 years old. In this study, we aimed to identify factors associated with inadequate screening defined as “no mammogram screening within past 2 years” to guide cancer prevention and early detection efforts.Methods: This study utilized area-based probabilistic sampling survey data, collected across Oregon in 2019. Dataset weights were calculated using a raking approach. Demographic and behavior information were collected with existing validated questionnaire items from national surveys. Weighted multivariable logistic regression analyses with missing-value imputations were conducted to identify factors associated with inadequate mammogram screening.Results: The study included 254 women 50-74 years-old without previous breast or ovarian cancer history. 19.29% of the sample reported no mammogram within two years, including 1.57% with no previous mammograms. Following unadjusted analyses, the significant factors included education, occupation status, health insurance and smoking and were therefore included into the adjusted model. In the multivariate adjusted model education remained significant while occupation status, health insurance and smoking were no longer significant. Compared to women with a college graduate degree, women with less than college graduate degree were at higher risk of inadequate screening [OR (95% CI) =3.23 (1.54, 6.74)].Conclusions: Lack of education was significantly associated with inadequate mammogram screening even after adjusting for occupation status, health insurance and smoking, which should prompt further outreach and education.
Changes in Body Size Phenotypes From Childhood to Adulthood and the Associated Cardiometabolic Outcomes, a Prospective Cohort Study
Authors: Du Tingting , Fonseca Vivian , Chen Wei , Bazzano Lydia 
Published: August 2021

Abstract
Background: Cardiometabolic outcomes associated with changes between body size phenotypes (defined by body mass index [BMI] together with metabolic status) over time have attracted attention recently. It remains unclear how metabolic health change from childhood to adulthood across different BMI categories and how such dynamic changes from childhood to adulthood might affect risk of cardiometabolic outcomes in adulthood. Therefore, we aimed to examine the effects of changes in body size phenotypes between childhood and adulthood on risks of diabetes and left ventricular hypertrophy (LVH) in adulthood.Methods: We included 3,351 individuals who participated as both children and adults in the Bogalusa Heart Study. The mean follow-up period was 36 years. Body size phenotypes for both children and adults were defined by harmonized criteria.Results: Compared with participants with persistently metabolically healthy normal weight (MHNW) from childhood to adulthood, MHNW children who became metabolically unhealthy in adulthood had increased diabetes burden and LVH risk in adulthood; Metabolically unhealthy normal weight (MUNW) children who became MHNW or metabolically healthy obese (MHO) as adults and individuals with persistent MHO from childhood to adulthood were not at increased risks of diabetes or LVH. The risks were increased if MHO during childhood transitioned to metabolically unhealthy obesity (MUO) by adulthood or MUO stayed from childhood to adulthood. MUO children who became MHO or MHNW as adults had decreased diabetes burden and LVH risk in adulthood.Conclusions: Individuals maintained MHO from childhood to adulthood and MUNW children who became MHO as adults had a diabetes burden and LVH risk similar to individuals with persistent MHNW. Progression to metabolically unhealthy status and maintenance of metabolically unhealthy status, regardless of childhood BMI status, were associated with increased cardiometabolic outcomes.
IVF/ICSI Outcomes of Euthyroid Infertile Women With TAI: Aspirin Plus Prednisone Treatment, Does It Matter?
Authors: Zhou Ping , Yao QiuPing , Yang Lihua , Yu Ya , Xie Jilai , Zhao Qiaohang , Feng Chun , Zhou Liming , Jin Min 
Published: August 2021

Abstract
Objective

Thyroid autoimmunity (TAI) per se has been demonstrated to be related to adverse pregnancy outcomes, including recurrent miscarriage and unexplained infertility. Although therapy of glucocorticoid to infertile remains controversial, aspirin combined with prednisone(P + A) are used frequently in antithyroid antibodies (ATA) positive infertile women in clinical practice.
Methods

A multicenter retrospective study was performed in the Second Affiliated Hospital of Zhejiang University School of Medicine, Ningbo Women and Children's Hospital and People's Hospital of Jinhua. We recruited 494 euthyroid infertile women positive for anti-thyroperoxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) with thyroid stimulating hormone 0.35-4.0mIU/L, who undergoing first in vitro fertilization and embryo transfer (IVF-ET) cycle during the period of 2017 to 2020. 346 women were ultimately recruited, including 187 patients receiving fresh embryo transfer and 159 patients receiving frozen-thawed embryo transfer. Among them, infertile 150 women were treated with prednisone(10mg/d) and aspirin(100mg/d), while the other 196 infertile women were untreated as control group. The treatment commenced on the day of embryo transfer and continued until the clinical pregnancy was determined by ultrasonography around 30 days after embryo transfer.
Results

Clinical pregnancy rate (CPR) of the first fresh embryo transfer cycle was 57.5% vs. 63.5% in control vs. in treated group (P = 0.414) and CPR was 57.8% versus 61.8% in the two groups in the frozen-thawed embryo transfer cycle(P = 0.606). Additionally, the prevalence of delivering a live birth at the fresh embryo transfer was 49.6% in the non-treatment group and 47.3% in the P + A treated group(P = 0.762). Cumulative CPR was similar in the groups at the fresh embryo transfer (control vs treated group: 56.9% vs 61.0%, P = 0.534). By conducting logistic regression, combined treatment of P + A appeared to have no influence on CPR or miscarriage rates (MR) at the first embryo transfer. Furthermore, the low but within the reference level of free triiodothyronine (FT3) was seen as a poor predictor of spontaneous abortion at the fresh embryo transfer.
Conclusions

To conclude, with regard to euthyroid women with TAI undergoing the first IVF-ET cycle, adjuvant treatment of P + A after the embryo transfer may be unnecessary irrespective of the fresh or frozen-thawed embryo transfer.