bluuebunny/crossref_metadata_2025_split huggingface dataset:
A predictive analytics model for differentiating between transient ischemic attacks (TIA) and its mimics
Authors: Stanciu Alia , Banciu Mihai , Sadighi Alireza , Marshall Kyle A. , Holland Neil R. , Abedi Vida , Zand Ramin 
Published: June 2020

Abstract
Background
Transient ischemic attack (TIA) is a brief episode of neurological dysfunction resulting from cerebral ischemia not associated with permanent cerebral infarction. TIA is associated with high diagnostic errors because of the subjective nature of findings and the lack of clinical and imaging biomarkers. The goal of this study was to design and evaluate a novel multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, to predict the likelihood of TIA, TIA mimics, and minor stroke.

Methods
We conducted our modeling on consecutive patients who were evaluated in our health system with an initial diagnosis of TIA in a 9-month period. We established the final diagnoses after the clinical evaluation by independent verification from two stroke neurologists. We used Recursive Feature Elimination (RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) for prediction modeling.

Results
The RFE-based classifier correctly predicts 78% of the overall observations. In particular, the classifier correctly identifies 68% of the cases labeled as “TIA mimic” and 83% of the “TIA” discharge diagnosis. The LASSO classifier had an overall accuracy of 74%. Both the RFE and LASSO-based classifiers tied or outperformed the ABCD2 score and the Diagnosis of TIA (DOT) score. With respect to predicting TIA, the RFE-based classifier has 61.1% accuracy, the LASSO-based classifier has 79.5% accuracy, whereas the DOT score applied to the dataset yields an accuracy of 63.1%.

Conclusion
The results of this pilot study indicate that a multinomial classification model, based on a combination of feature selection mechanisms coupled with logistic regression, can be used to effectively differentiate between TIA, TIA mimics, and minor stroke.
E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation
Authors: Wang Qixin , Sundar Isaac K. , Li Dongmei , Lucas Joseph H. , Muthumalage Thivanka , McDonough Samantha R. , Rahman Irfan 
Published: June 2020

AbstractElectronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.
Do acute changes in ambient air pollution increase the risk of potentially fatal cardiac arrhythmias in patients with implantable cardioverter defibrillators?
Authors: Dales Robert , Lee Douglas S. , Wang Xuesong , Cakmak Sabit , Szyszkowicz Mieczyslaw , Shutt Robin , Birnie David 
Published: June 2020

Abstract
Background
Daily changes in ambient air pollution have been associated with cardiac morbidity and mortality. Precipitating a cardiac arrhythmia in susceptible individuals may be one mechanism. We investigated the influence of daily changes in air pollution in the Province of Ontario, Canada on the frequency of discharges from implantable cardio defibrillators (ICDs) which occur in response to potentially life threatening arrhythmias.

Methods
Using a case- crossover design, we compared ambient air pollution concentrations on the day of an ICD discharge to other days in the same month and year in 1952 patients. We adjusted for weather, lagged the exposure data from 0 to 3 days, and stratified the results by several patient-related characteristics.

Results
Median (interquartile range) for ozone (O3), fine particulate matter (PM2.5), sulphur dioxide (SO2) and nitrogen dioxide (NO2) were 26.0 ppb (19.4, 33.0), 6.6 μg/m3 (4.3, 10.6), 1.00 ppb (0.4,2.1), 10.0 ppb (6.0,15.3) respectively. Unlagged odds ratios (95%) for an ICD discharge associated with an interquartile range increase in pollutant were 0.97 (0.86, 1.09) for O3, 0.99 (0.92, 1.06) for PM2.5, 0.97 (0.91, 1.03) for SO2, and 1.00 (0.89, 1.12) for NO2.

Conclusion
We found no evidence that the concentrations of ambient air pollution observed in our study were a risk factor for potentially fatal cardiac arrhythmias in patients with ICDs.
The relationship between total cholesterol and postpartum impaired glucose tolerance in women with gestational diabetes mellitus
Authors: Wang Dongyu , Ding Wenjing , Xu Shuqia , Chen Haitian , Liu Bin , Wang Zilian 
Published: June 2020

Abstract
Background
History of gestational diabetes mellitus (GDM) and serum lipid abnormalities were associated with postpartum impaired glucose tolerance. To investigate the association between concentration of total cholesterol (TC), at the time of GDM diagnosis, and risk of postpartum glucose intolerance.

Methods
Women who were diagnosed GDM with a live singleton delivery between January 1, 2013 and December 31, 2017 were included. Women were grouped based on the TC quartiles at the time of GDM diagnosis and had an OGTT at 6–12 weeks after delivery. The relationship between TC and the risk of postpartum glucose intolerance was assessed by COX regression.

Results
A total of 845 women were in the final analysis. Higher TC quartile at diagnosis of GDM was associated with a decreased risk of postpartum glucose intolerance. Women in the highest TC quartile (>7.0 mmol L− 1) had approximately only half-risk of any postpartum glucose intolerance, compared with women in the lowest TC quartile (<5.5 mmol L− 1).

Conclusions
The decreased concentration of TC, at the time of GDM diagnosis, was related to an increased risk of postpartum abnormal glucose regulation in GDM women. Therefore, because both excessively increased and decreased TC were associated with pregnancy and postpartum complications, the optimal concentration of maternal TC throughout pregnancy remained to be further researched.
LDL-cholesterol to HDL-cholesterol ratio discordance with lipid parameters and carotid intima-media thickness: a cohort study in China
Authors: Lou Yanmei , Li Xue , Cao Liming , Qin Pei , Shi Jing , Zhang Yanyan , Wang Changyi , Ma Jianping , Wang Li , Peng Xiaolin , Chen Hongen , Xu Shan , Hu Fulan , Zhao Yashuang , Zhao Ping 
Published: June 2020

Abstract
Background
The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China.

Methods
In total, 13,612 adults who didn’t have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk.

Results
During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P < 0.001). A low LDL-C/HDL-C ratio with discordantly normal HDL-C and high LDL-C (13.2% of individuals) had a 32% (HR = 1.32, 95% CI 1.11, 1.57) higher risk of elevated CIMT than concordantly low LDL-C and normal HDL-C. Sensitivity analysis by excluding CIMT developed in the first 2 years follow-up further confirmed the above results.

Conclusions
A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.
The four of structural genes sequences of a porcine epidemic diarrhea virus from domestic piglet in Fujian, China
Authors: Dong Bo , Dai Ailing , Li Xiaohua , Yang Xiaoyan 
Published: June 2020

AbstractA prevalent PEDV strain, designated FJLY06, was isolated from Fujian, China. The four of structural genes sequences of PEDV obtained were analyzed to determine their phylogenetic relationships and homology respectively, revealing that FJLY06 was highly homologous to virulent PEDV strains. The four structural genes all differed genetically from the vaccine strain CV777. The sequence alignment results further showed that N, M and E genes of Chinese PEDV strains is highly conserved. Compared with the vaccine strain CV777, 8 mutations were detected in COE of FJLY06 S gene. The recombination analysis revealed FJLY06 is similar to other pandemic strains in China with a variant S gene, and maybe a reason for recent vaccination failures.
KLF4 defines the efficacy of the epidermal growth factor receptor inhibitor, erlotinib, in triple-negative breast cancer cells by repressing the EGFR gene
Authors: Roberts Melyssa S. , Anstine Lindsey J. , Finke Viviane S. , Bryson Benjamin L. , Webb Bryan M. , Weber-Bonk Kristen L. , Seachrist Darcie D. , Majmudar Parth R. , Keri Ruth A. 
Published: June 2020

Abstract
Background
Triple-negative breast cancer (TNBC) is characterized by high rates of recurrence and poor overall survival. This is due, in part, to a deficiency of targeted therapies, making it essential to identify therapeutically targetable driver pathways of this disease. While epidermal growth factor receptor (EGFR) is expressed in 60% of TNBCs and drives disease progression, attempts to inhibit EGFR in unselected TNBC patients have had a marginal impact on outcomes. Hence, we sought to identify the mechanisms that dictate EGFR expression and inhibitor response to provide a path for improving the utility of these drugs. In this regard, the majority of TNBCs express low levels of the transcription factor, Krüppel-like factor 4 (KLF4), while a small subset is associated with high expression. KLF4 and EGFR have also been reported to have opposing actions in TNBC. Thus, we tested whether KLF4 controls the expression of EGFR and cellular response to its pharmacological inhibition.

Methods
KLF4 was transiently overexpressed in MDA-MB-231 and MDA-MB-468 cells or silenced in MCF10A cells. Migration and invasion were assessed using modified Boyden chamber assays, and proliferation was measured by EdU incorporation. Candidate downstream targets of KLF4, including EGFR, were identified using reverse phase protein arrays of MDA-MB-231 cells following enforced KLF4 expression. The ability of KLF4 to suppress EGFR gene and protein expression and downstream signaling was assessed by RT-PCR and western blot, respectively. ChIP-PCR confirmed KLF4 binding to the EGFR promoter. Response to erlotinib in the context of KLF4 overexpression or silencing was assessed using cell number and dose-response curves.

Results
We report that KLF4 is a major determinant of EGFR expression and activity in TNBC cells. KLF4 represses transcription of the EGFR gene, leading to reduced levels of total EGFR, its activated/phosphorylated form (pEGFR), and its downstream signaling intermediates. Moreover, KLF4 suppression of EGFR is a necessary intermediary step for KLF4 to inhibit aggressive TNBC phenotypes. Most importantly, KLF4 dictates the sensitivity of TNBC cells to erlotinib, an FDA-approved inhibitor of EGFR.

Conclusions
KLF4 is a major regulator of the efficacy of EGFR inhibitors in TNBC cells that may underlie the variable effectiveness of such drugs in patients.
instaGRAAL: chromosome-level quality scaffolding of genomes using a proximity ligation-based scaffolder
Authors: Baudry Lyam , Guiglielmoni Nadège , Marie-Nelly Hervé , Cormier Alexandre , Marbouty Martial , Avia Komlan , Mie Yann Loe , Godfroy Olivier , Sterck Lieven , Cock J. Mark , Zimmer Christophe , Coelho Susana M. , Koszul Romain 
Published: June 2020

AbstractHi-C exploits contact frequencies between pairs of loci to bridge and order contigs during genome assembly, resulting in chromosome-level assemblies. Because few robust programs are available for this type of data, we developed instaGRAAL, a complete overhaul of the GRAAL program, which has adapted the latter to allow efficient assembly of large genomes. instaGRAAL features a number of improvements over GRAAL, including a modular correction approach that optionally integrates independent data. We validate the program using data for two brown algae, and human, to generate near-complete assemblies with minimal human intervention.
Methotrexate-loaded multifunctional nanoparticles with near-infrared irradiation for the treatment of rheumatoid arthritis
Authors: Ha You-Jung , Lee Sun-Mi , Mun Chin Hee , Kim Hyung Joon , Bae Yonghee , Lim Ji-Hee , Park Kyu-Hyung , Lee Soo-Kon , Yoo Kyung-Hwa , Park Yong-Beom 
Published: June 2020

AbstractBackgroundsDespite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects.MethodsAu film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice.ResultsUpon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone.ConclusionsA combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.
Proteomic analysis in lupus mice identifies Coronin-1A as a potential biomarker for lupus nephritis
Authors: Nicolaou Orthodoxia , Sokratous Kleitos , Makowska Zuzanna , Morell María , De Groof Aurélie , Montigny Pauline , Hadjisavvas Andreas , Michailidou Kyriaki , Oulas Anastasis , Spyrou George M. , Demetriou Christiana , Alarcón-Riquelme Marta E. , Psarellis Savvas , Kousios Andreas , Lauwerys Bernard , Kyriacou Kyriacos 
Published: June 2020

Abstract
Background
Approximately 50% of systemic lupus erythematosus (SLE) patients develop nephritis, which is among the most severe and frequent complications of the disease and a leading cause of morbidity and mortality. Despite intensive research, there are still no reliable lupus nephritis (LN) markers in clinical use that can assess renal damage and activity with a high sensitivity and specificity. To this end, the aim of this study was to identify new clinically relevant tissue-specific protein biomarkers and possible underlying molecular mechanisms associated with renal involvement in SLE, using mass spectrometry (MS)-based proteomics.

Methods
Kidneys were harvested from female triple congenic B6.NZMsle1/sle2/sle3 lupus mice model, and the respective sex- and age-matched C57BL/6 control mice at 12, 24 and 36 weeks of age, representing pre-symptomatic, established and end-stage LN, respectively. Proteins were extracted from kidneys, purified, reduced, alkylated and digested by trypsin. Purified peptides were separated by liquid chromatography and analysed by high-resolution MS. Data were processed by the Progenesis QIp software, and functional annotation analysis was performed using DAVID bioinformatics resources. Immunofluorescence and multiple reaction monitoring (MRM) MS methods were used to confirm prospective biomarkers in SLE mouse strains as well as human serum samples.

Results
Proteomic profiling of kidney tissues from SLE and control mice resulted in the identification of more than 3800 unique proteins. Pathway analysis revealed a number of dysregulated molecular pathways that may be mechanistically involved in renal pathology, including phagosome and proximal tubule bicarbonate reclamation pathways. Proteomic analysis supported by human transcriptomic data and pathway analysis revealed Coronin-1A, Ubiquitin-like protein ISG15, and Rho GDP-dissociation inhibitor 2, as potential LN biomarkers. These results were further validated in other SLE mouse strains using MRM-MS. Most importantly, experiments in humans showed that measurement of Coronin-1A in human sera using MRM-MS can segregate LN patients from SLE patients without nephritis with a high sensitivity (100%) and specificity (100%).

Conclusions
These preliminary findings suggest that serum Coronin-1A may serve as a promising non-invasive biomarker for LN and, upon validation in larger cohorts, may be employed in the future as a screening test for renal disease in SLE patients.
Sacrococcygeal teratoma with preterm delivery: a case report
Authors: Baró Anna Moreno , Perez Silvia Pina , Costa Montserrat Mestre , Heredia Cristina Lesmes , Azuara Laura Serra , Juanos Judith Lleberia , Lapiedra Marc Zamora 
Published: June 2020

Abstract
Background
Sacrococcygeal teratoma is one of the most frequently prenatally diagnosed neoplasias. Obstetric ultrasound has a role in the diagnosis and management of these tumors during pregnancy. In this report, we describe a multidisciplinary approach in a case of a patient with sacrococcygeal teratomas and preterm delivery, as well as postnatal outcomes.

Case presentation
A 26-year-old Caucasian woman at 20.3 weeks of gestation with a normal gestational course and no relevant medical or surgical history was referred to our institution with a sacrococcygeal mass diagnosis. Magnetic resonance imaging confirmed the diagnosis of sacrococcygeal teratoma type I according to the Altman classification. Follow-up with ultrasound showed an increase in the size of the mass up to 190 × 150 mm, high Doppler flow, and severe polyhydramnios. At 35.1 weeks of gestation, the patient had premature rupture of membranes, and an emergency cesarean section was performed due to recurrent late decelerations detected by fetal heart rate monitoring. Afterward, surgery was performed successfully at 36 hours of life. Posterior controls revealed normal and healthy child growth.

Conclusions
This case report demonstrates the importance of a multidisciplinary approach to offer the best neonatal outcomes by performing early surgery, as well as the need for follow-up by ultrasound in order to minimize complications by assessing mass growth, Doppler flow, and amniotic fluid.
Novel venom-based peptides (P13 and its derivative—M6) to maintain self-renewal of human embryonic stem cells by activating FGF and TGFβ signaling pathways
Authors: Ma Rui , Ren Zhili , Li Bin , Siu Shirley W. I. , Chen Guokai , Kwok Hang Fai 
Published: June 2020

Abstract
Background
In our previous study, a venom-based peptide named Gonearrestide (also named P13) was identified and demonstrated with an effective inhibition in the proliferation of colon cancer cells. In this study, we explored if P13 and its potent mutant M6 could promote the proliferation of human embryonic stem cells and even maintain their self-renewal.

Methods
The structure-function relationship analysis on P13 and its potent mutant M6 were explored from the molecular mechanism of corresponding receptor activation by a series of inhibitor assay plus molecular and dynamics simulation studies.

Results
An interesting phenomenon is that P13 (and its potent mutant M6), an 18AA short peptide, can activate both FGF and TGFβ signaling pathways. We demonstrated that the underlying molecular mechanisms of P13 and M6 could cooperate with proteoglycans to complete the “dimerization” of FGFR and TGFβ receptors.

Conclusions
Taken together, this study is the first research finding on a venom-based peptide that works on the FGF and TGF-β signaling pathways to maintain the self-renewal of hESCs.
Hermite–Hadamard inequality for fractional integrals of Caputo–Fabrizio type and related inequalities
Authors: Gürbüz Mustafa , Akdemir Ahmet Ocak , Rashid Saima , Set Erhan 
Published: June 2020

AbstractIn this article, firstly, Hermite–Hadamard’s inequality is generalized via a fractional integral operator associated with the Caputo–Fabrizio fractional derivative. Then a new kernel is obtained and a new theorem valid for convex functions is proved for fractional order integrals. Also, some applications of our main findings are given.