bluuebunny/crossref_metadata_2025_split huggingface dataset:
BeCaked: An Explainable Artificial Intelligence Model For COVID-19 Forecasting
Authors: Nguyen Duc , Vo Nghia , Nguyen Thinh , Nguyen Khuong , Nguyen Quang , Tran Dang , Quan Tho 
Published: May 2021

Abstract
From the end of 2019, one of the most serious and largest spread pandemics occurred in Wuhan (China) named Coronavirus (COVID-19). As reported by the World Health Organization, there are currently more than 100 million infectious cases with an average mortality rate of about five percent all over the world. To avoid serious consequences on people’s lives and the economy, policies and actions need to be suitably made in time. To do that, the authorities need to know the future trend in the development process of this pandemic. This is the reason why forecasting models play an important role in controlling the pandemic situation. However, the behavior of this pandemic is extremely complicated and difficult to be analyzed, so that an effective model is not only considered on accurate forecasting results but also the explainable capability for human experts to take action pro-actively.
With the recent advancement of Artificial Intelligence (AI) techniques, the emerging Deep Learning (DL) models have been proving highly effective when forecasting this pandemic future from the huge historical data. However, the main weakness of DL models is lacking the explanation capabilities. To overcome this limitation, we introduce a novel combination of the Susceptible-Infectious-Recovered-Deceased (SIRD) compartmental model and Variational Autoencoder (VAE) neural network known as BeCaked. With pandemic data provided by the Johns Hopkins University Center for Systems Science and Engineering, our model achieves 0.98 R2 and 0.012 MAPE at world level with 31-step forecast and up to 0.99 R2 and 0.0026 MAPE at country level with 15-step forecast on predicting daily infectious cases. Not only enjoying high accuracy, but BeCaked also offers useful justifications for its results based on the parameters of the SIRD model. Therefore, BeCaked can be used as a reference for authorities or medical experts to make on-time right decisions.
Identification of The Key miRNAs And Target Genes In Basal Cell Carcinoma By Bioinformatics Analysis
Authors: Liu Hao , Chen Ling 
Published: May 2021

Abstract
Background The highly tissue-destructive and localized accumulation of basal cell carcinoma(BCC) makes it one of the most important cancers affecting people's lives. Existing therapeutic approaches, including surgical treatment, chemotherapy, and Hedgehog pathway inhibitors, have failed to achieve broad therapeutic effects for various reasons. This study aims to explore additional potential therapeutic targets and possible diagnostic and prognostic biomarkers using bioinformatics analysis.Material/Methods The Gene Expression Omnibus (GEO) database identified the microarray dataset GSE34535. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between BCC and non-lesional skin. Potential target genes of DE-miRNA were screened using the miRWalk, mirDIP and miRTarBase databases. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes were established using the DAVID database. Protein–protein interaction network and miRNA-hub gene network were analyzed based on the STRING database and visualized by Cytoscape software. Results 51 up-regulated DE-miRNAs and 38 down-regulated DE-miRNAs were identified from the BCC samples. miR-455-5p was mainly up-regulated and miR-139-5p was mainly down-regulated. Two key bub genes MAPK1 and EGFR were identified in the PPI network. Four out of the ten hub genes were regulated by up-regulated miR-18a and four by down-regulated miR-133b. Viral infections were also identified in the study.Conclusions Bioinformatics identified four miRNAs and two important hub genes that may be associated with BCC, and it was suggested that viruses may play a role in BCC.
Hidden Blood Loss in Percutaneous Endoscopic Lumbar Discectomy (PELD): a Prospective Study
Authors: Chen Chong , Xiao Dan , Gu Honglin , Liang Guoyan , Zhang Ruiying , Zheng Xiaoqing , Liang Changxiang , Chang Yunbing 
Published: May 2021

Abstract
Background: Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive technique for treatment of lumbar disc herniation (LDH) that requires only an eight-mm skin incision and promotes faster recovery. It is widely believed that the procedure is associated with minimal blood loss. However, significant perioperative hidden blood loss (HBL) is frequently unaccounted for. This study aimed to investigate HBL and peri-operative factors contributing to HBL in a series of individuals undergoing PELD.Methods: As a prospective observational study, 156 patients, mean age 41.6 years (ranged from 17 to 71), undergoing PELD were finally enrolled between May 2019 and November 2020. The analyzed factors included gender, age, body mass index (BMI), symptom duration, operation approach/technique, operation duration, the presence of associated chronic diseases (e.g., hypertension, rheumatoid arthritis, and diabetes mellitus), and improvements in Visual Analog Scale (VAS), Japanese Orthopedic Association (JOA), and Oswestry Disability Index (ODI) scores. Gross’s formula was applied to calculate blood loss from recorded values for patient height, weight, and hematocrit levels before and after surgery. Multivariate linear regression analysis and t test were performed to identify factors that contributed significantly to HBL.Results: The mean HBL during PELD was 201 ± 126 mL, and the Hb reduction observed post-operatively was 7.4 ± 4.5 g/L. A lateral surgical approach was associated with greater HBL compared with an interlaminar approach. However, no significant differences in VAS, JOA, and ODI score improvements were noted between the two surgical approaches. Increased surgical times and foraminal decompression were identified by multivariate linear regression analysis as linked to increased HBL. As expected, the occurrence of post-operative anemia was significantly associated with HBL. Age, gender, BMI, symptom duration, and associated chronic diseases showed no association with increased HBL during PELD. Conclusions: HBL is increased in PELD patients with long surgical times and lumbar foraminal decompression.
Statin therapy inhibits fatty acid synthase via dynamic protein modifications
Authors: Trub Alec , Wagner Greggory , Crown Scott , Zhang Guo-Fang , Thompson J. Will , Ilkayeva Olga , Stevens Robert , Grimsrud Paul , Backos Donald , Hirschey Matthew 
Published: May 2021

Abstract
Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the reactive HMG-CoA into mevalonate. Recent discoveries revealed HMG-CoA is a highly reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins would increase HMG-CoA levels and subsequent protein modifications. We found a strong increase in HMG-CoA levels, but only a single protein being modified. Fatty acid synthase (FAS) was modified on active site residues and, importantly, the modification is located on non-lysine residues. The dynamic modifications occur only on a subpool of FAS that is located near HMGCR and alters cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner.
The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes
Authors: Gao Yinjie , Ma Xiaosen , Wang Huiping , Cui Yunying , Zhang Yushi , Nie Min , Tong Anli 
Published: May 2021

Abstract
BackgroundPrevious studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs), and several potential genes were found with high expressions. PurposeWe aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. MethodsThis study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment, as well as protein-protein interaction (PPI) network, were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with non-functioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. ResultsIn this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis (GO: 0055074, n = 3, p = 2.00X10-4). In the KEGG pathway analysis, calcium signaling pathway (hsa04020, n = 8, p= 4.38X10-6) and the aldosterone synthesis and secretion (hsa04925, n = 6, p = 8.73X10-6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4 and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p<0.001, 3.753 folds of NFA, p=0.002 and 11.487 folds of NFA, p=0.018).ConclusionIn summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. And the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.
A New Risk Model Predicting Overall Survival Using Preoperative Nutritional and Inflammation Status (NIS) in Patients After Curative Resection of Colorectal Cancer
Authors: Hayama Tamuro , Ozawa Tsuyoshi , Tsukamoto Mitsuo , Fukushima Yoshihisa , Shimada Ryu , Nozawa Keijiro , Matsuda Keiji , Fujii Shoichi , Fukagawa Takeo , Hashiguchi Yojiro 
Published: May 2021

Abstract
It has been shown that nutritional status correlates with survival in patients with various kinds of cancers. Besides, cancer causes inflammation which has been suggested to stimulate cancer progression. Therefore, inflammation status also has shown to reflect prognosis of cancers. In this study, we evaluated several kinds of nutritional and inflammation parameters in preoperative blood samples and constructed new risk model predicting a survival in patients with CRC (colorectal cancers). We retrospectively examined 286 patients with stage I-III CRC who had undergone curative resection in Teikyo University Hospital between 2013 to 2017. The association between overall survival (OS) and preoperative body mass index, albumin (Alb), cholesterol (Chol), and lymphocyte count, white blood cell count (WBC), neutrophil count (Neu), platelet count (Plt), C-reactive protein (CRP) were examined using Kaplan-Meier curve and log rank test. and eventually Alb, Chol, Neu, Plt, and CRP were shown to correlate with OS. Alb, Chol, Neu, Plt, and CRP were shown to correlate with OS. We constructed a new risk model (NIS: nutrition inflammation status) using these factors, and compared its usefulness with known models such as CRP-albumin ratio (CAR), Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and neutrophil lymphocyte ratio (NLR). NIS prepared using nutritional indicators and inflammatory findings was useful as a new model for predicting overall survival in patients undergoing curative resection for CRC, compared with known models.
An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output
Authors: Smieszek Sandra P. , Brzezynski Jennifer L. , Kaden Alyssa R. , Shinn Jordan A. , Wang Jingyuan , Xiao Changfu , Polymeropoulos Christos , Özçelik Tayfun , Polymeropoulos Mihael 
Published: May 2021

Abstract
We conducted an observational research study to collect information on sleep-wake patterns from participants with a confirmed status of the cryptochrome circadian clock 1 (CRY1) splicing variant, CRY1Δ11 c.1657+3A>C, and their controls, defined as wild-type (WT) family members. Altogether, 67 participants were enrolled and completed this study in Turkey, recruited from a list of families with at least one CRY1-confirmed member. We measured sleep-wake patterns and metabolic output, specifically time and frequency of bowel movements, for all participants by daily post-sleep diaries over 28 days. The sleep diary measured self-reported bed time, wake time, midpoint of sleep, and latency to persistent sleep (LPS), and accounted for naps and awakenings for religious purposes. Wake time and midpoint of sleep were significantly later in the CRY1Δ11 variant group versus WT, and LPS was significantly greater in participants in the CRY1Δ11 variant group. The mean bed time on all nights of sleep was later in participants with a CRY1Δ11 variant versus WT. Additionally, participants with a CRY1Δ11 variant had significantly affected metabolic outputs, measured by later bowel movements than WT participants. These results demonstrate that, on average, individuals with the studied splicing variant experience pronounced delays in sleep period and circadian-related metabolic processes.
TRIM59 is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Neuroendocrine Differentiation in Prostate Cancer
Authors: Fan Liancheng , Gong Yiming , He Yuman , Gao Wei-Qiang , Dong Baijun , Zhu Helen He , Xue Wei 
Published: May 2021

Abstract
Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.
Scutellarin acts on the AR-NOX Axis to Remediate Oxidative Stress Injury in a Mouse Model of Cerebral Ischemia/Reperfusion Injury
Authors: Peng Llin , Deng Minzhen , Huang Yan , Wu Shuang , Cao Yucheng , Gao Zhijie , Wu Xiaoli , Zhou Lihua , Chung Sookja Kim , Sun Jingbo , Cheng Xiao 
Published: May 2021

Abstract
BackbroundOxidative stress plays an important role in the ischemic stroke induced brain damage. Our previous study showed that Scutellarin protects against ischemic injury in vitro and in vivo induced oxidative damage in rats, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of Scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism.MethodsC57BL/6N mice (Wild-type, WT) and AR knockout (AR-/-) mice were subjected to transient middle cerebral artery occlusion (tMCAO) model with 1h occlusion followed by 3d reperfusion, and Scutellarin was administered from 2h before surgery to 3 days after surgery. Subsequently, Neurological function were assessed by the modified Longa score method, the histopathological morphology observed with 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the levels of ROS, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHDG), Neurotrophin-3 (NT-3), poly ADP-ribose polymerase-1 (PARP1) and 3-nitrotyrosine (3-NT) in the ischemic penumbra regions. Quantitative proteomics profiling using quantitative nano-HPLC-MS/MS were performed to compare the protein expression difference between AR-/- and WT mice with or without tMCAO injury. The expression of AR, NOX1, NOX2 and NOX4 in the ipsilateral side of ischemic brain were detected by Real time-PCR, Western blot and immunofluorescence co-staining with NeuN.ResultsScutellarin treatment alleviated brain damage suffered from tMCAO injury such as improved neurological function deficit, brain infarct area and neuronal injury and reduced the expression of oxidation-related products, moreover, also down-regulated tMCAO induced AR mRNA and protein expression.ConclusionsScutellarin would be a potential drug for the treatment of ischemic stroke through regulating AR-NOX Axis modulate oxidative stress injury to play the protective role of cerebral ischemia injury.
Surgical and Percutaneous Revascularization Outcomes based on SYNTAX I, II, and Residual Scores. A Long-Term follow-up Study.
Authors: Martins Eduardo Bello , Hueb Whady , Brown David L , Scudeler Thiago Luis , Lima Eduardo Gomes , Rezende Paulo Cury , Soares Paulo Rogério , Garzillo Cibele Larrosa , Filho Jaime Paula Pessoa Linhares , Batista Daniel Valente , Ramires Jose Antonio Franchini , Filho Roberto Kalil 
Published: May 2021

Abstract
BackgroundThe objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up.MethodsThis is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. Clinical endpoints were the first occurrence of a composite of overall death, myocardial infarction (MI), stroke, or repeat revascularization (MACCE) and the total occurrence of each component of MACCE.ResultsIn the CABG sample, SSI had a median of 23 (IQR:17-29.5), median SSII of 25.4 (IQR:19.2-32.8), and median rSS of 2 (IQR:0-6.5); in PCI SSI had a median of 14 (IQR:10-19.1), median SSII of 28.7 (IQR:23-34.2), and median rSS of 4.7 (IQR:0-9). Total of 174 events were documented and CABG patients had a lower rate of MACCE (15.6% versus 21.2%; adjusted HR: 1.98; 95% CI, 1.13-3.47; P=.016) and repeat revascularization (3.8% versus 11.5%; adjusted HR: 4.35; CI 95%: 1.74-10.85; P=.002) compared with PCI. No SYNTAX score tertile found a difference in death rate between procedures. In a multivariate analysis, the rSS was an independent predictor for MACCE (HR=1.04; 95% CI, 1.01-1.06; P=.001). Regarding death, the only independent predictors were ejection fraction and renal function.Conclusion﻿Surgical revascularization resulted in a more complete revascularization and lower rates of major cardiac or cerebrovascular events in a long-term follow-up. Also, grading the incompleteness of revascularization through the residual SYNTAX score identified a higher event rate, suggesting that complete revascularization is associated with a better prognosis.
Hepatitis B Virus-Associated Follicular Lymphoma Reveals T-Cell Inflamed Phenotype and Response to Lenalidomide
Authors: Wang Nan , Qin Wei , Zheng Zhong , Zhao Ming , Xiong Jie , Fang Hai , Sun Rui , Wang Yichao , Li Chen , Dong Lei , Sun Xiaojian , Wang Li , Xu Pengpeng , Cheng Shu , Xu Haimin , Zhang Fan , Zhao Weili 
Published: May 2021

Abstract
Background: Follicular lymphoma (FL) is a malignancy of lymphocytes derived from germinal center (GC). Hepatitis B virus (HBV) infection may increase the incidence of FL. Here, we performed an integrated genomic and transcriptomic analysis to identify molecular characteristics and therapeutic targets for HBV-associated FL.Methods: A total of 253 patients with newly diagnosed FL were enrolled. Whole-genome sequencing (n=13) and whole-exome sequencing (n=87) were performed on tumor samples of 100 patients. Among them, 84 patients were available for transcriptomic sequencing data. Moreover, biological function of immune modulator TNFAIP3 mutation was investigated in vitro using FL cell line SC-1 and in vivo using zebrafish xenograft model.Results: By characterizing altogether 253 FL patients, we showed that patients with HBV infection (surface antigen positive, HBsAg+) were significantly associated with younger age, more frequent spleen involvement, advanced histological grade, higher proliferation index, and poorer progression-free survival. By whole-genome/exome and targeted sequencing, we observed increased mutations in immune modulators (TNFAIP3, CD70, CXCR4, PIM1, KLF2, FAS, CD58, and CD83), decreased mutations in epigenetic modifiers (KMT2D and CREBBP), and low incidence of BCL2 translocation as the core oncogenic program of HBsAg+ FL. By transcriptomic sequencing, we further showed that HBsAg+ FL was enriched by immune-related pathways, antigen processing and presentation and IFN signatures, as well as inflamed signatures and infiltration of CD8+T and Th1 cells, with malignant lymphocytes transiting to post-GC phenotype. In the co-culture system of FL cell line SC-1 with peripheral blood mononuclear cells mimicking in vivo situation, TNFAIP3 mutations induced overexpression of TIGIT on CD8+T cells and VISTA on Th1 cells, both of which were downregulated by lenalidomide, resulting in sensitivity of TNFAIP3-mutant cells to lenalidomide treatment in co-culture system and in zebrafish xenograft model. Of note, negative prognostic impact of HBV infection on patients treated with rituximab-based immunochemotherapy could be overcome by rituximab and lenalidomide.Conclusions: HBV-associated FL may be considered as a specific subtype, based on distinct immune modulator mutations, and CD8+T- and Th1-enriched post-GC phenotype. Moreover, these findings provided new insights into the pathogenetic role of HBV in FL and the potential benefit of immunomodulatory agents in treating HBV-associated FL.