bluuebunny/crossref_metadata_2025_split huggingface dataset:
MSIFinder: a python package for detecting MSI status using random forest classifier
Authors: Zhou Tao , Chen Libin , Guo Jing , Zhang Mengmeng , Zhang Yanrui , Cao Shanbo , Lou Feng , Wang Haijun 
Published: April 2021

Abstract
Background
Microsatellite instability (MSI) is a common genomic alteration in colorectal cancer, endometrial carcinoma, and other solid tumors. MSI is characterized by a high degree of polymorphism in microsatellite lengths owing to the deficiency in the mismatch repair system. Based on the degree, MSI can be classified as microsatellite instability-high (MSI-H) and microsatellite stable (MSS). MSI is a predictive biomarker for immunotherapy efficacy in advanced/metastatic solid tumors, especially in colorectal cancer patients. Several computational approaches based on target panel sequencing data have been used to detect MSI; however, they are considerably affected by the sequencing depth and panel size.

Results
We developed MSIFinder, a python package for automatic MSI classification, using random forest classifier (RFC)-based genome sequencing, which is a machine learning technology. We included 19 MSI-H and 25 MSS samples as training sets. First, we selected 54 feature markers from the training sets, built an RFC model, and validated the classifier using a test set comprising 21 MSI-H and 379 MSS samples. With this test set, MSIFinder achieved a sensitivity (recall) of 1.0, a specificity of 0.997, an accuracy of 0.998, a positive predictive value of 0.954, an F1 score of 0.977, and an area under the curve of 0.999. To further verify the robustness and effectiveness of the model, we used a prospective cohort consisting of 18 MSI-H samples and 122 MSS samples. MSIFinder achieved a sensitivity (recall) of 1.0 and a specificity of 1.0. We discovered that MSIFinder is less affected by a low sequencing depth and can achieve a concordance of 0.993 while exhibiting a sequencing depth of 100×. Furthermore, we realized that MSIFinder is less affected by the panel size and can achieve a concordance of 0.99 when the panel size is 0.5 M (million bases).

Conclusion
These results indicate that MSIFinder is a robust and effective MSI classification tool that can provide reliable MSI detection for scientific and clinical purposes.
Relationship between small dense low density lipoprotein and cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Zhang Jianwei , He Lingjie 
Published: April 2021

Abstract
Background
Residual risk remained significant despite effective low density lipoprotein cholesterol (LDL-C) lowering treatment. Small dense low density lipoprotein cholesterol (sdLDL-C) as part of LDL-C has been found to be predictor of coronary heart disease (CHD) and cardiovascular (CV) events in patients with stable CHD independently of LDL-C. However, to date, few studies have explored the role of sdLDL-C in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Accordingly, this study aimed to evaluate the association of sdLDL-C with CV events in patients with ACS undergoing PCI.

Methods
Patients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The risk of sdLDL-C for CV events was compared according to sdLDL-C quartiles. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCE), which was the composite of all cause of death, nonfatal myocardial infarction (MI), nonfatal stroke or unplanned repeat revascularization. A Cox proportional hazards regression model was performed to estimate the risk of CV events. Subgroup analysis according to diabetes status and LDL-C were performed separately for MACCE.

Results
A total of 6092 patients were included in the analysis (age: 60.2 ± 10.13 years, male: 75.3%, BMI: 25.9 ± 3.33 kg/m2, dyslipidemia: 74.1% and diabetes: 44.5%). During 18 months of follow-up, 320 (5.2%) incident CV events occurred. Compared to the lowest sdLDL-C quartile group, patients in the highest quartile had a greater risk of CV events after multivariable adjustment (HR 1.92; 95% CI 1.37–2.70). In addition, it was mainly due to the increase of unplanned repeat revascularization. In the subgroup analyses, significant association was observed regardless of level of LDL-C and diabetes status.

Conclusions
Patients with elevated sdLDL-C have a higher risk of CV events in Chinese patients with ACS undergoing PCI, providing additional value for better risk assessment.
MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
Authors: Zhang Fan , Cheng Naixuan , Du Jie , Zhang Haibo , Zhang Congcong 
Published: April 2021

Abstract
Background
Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered.

Methods
The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H2O2 and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX.

Results
250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition.

Conclusions
Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS.
Antibiotic prescriptions for children younger than 5 years with acute upper respiratory infections in China: a retrospective nationwide claims database study
Authors: Xue Fengxia , Xu Baoping , Shen Adong , Shen Kunling 
Published: April 2021

Abstract
Background
In China, there were few studies to estimate antibiotic use for children with upper respiratory infections at the national level. The aim of this study was to describe the antibiotic prescribing practice for children aged < 5 years old with upper respiratory infections (URIs) using a nationwide claims database.

Methods
This was a retrospective cross-sectional study using a sampled database from the China Health Insurance Research Association (CHIRA). Study subjects included children younger than 5 years with outpatient visits in 2015 that resulted in a diagnosis of a upper respiratory infection. We calculated the percentage of visits who received antibiotics, the proportion of injection formulations, the percentage of combined antibiotics and the proportion of each antibiotic class. The patterns of antibiotic prescription were also described by medical institution type, city level and geographical region.

Results
Among the 92,821 visits, 27.1% were prescribed antibiotics, of which 27.0% received injection formulations. The rate of antibiotic prescribing varied by age group (P < 0.001), with the lowest (16.0%) in infants and the highest in patients at age 3 to < 4 years (29.9%) and age 4 to < 5 years (32.5%). The Midwestern region, underdeveloped cities and low-level hospitals represented relatively higher rates of prescribing antibiotics (P < 0.001) and higher proportions of injection dosage forms (P < 0.001). The most 3 common antibiotic classes prescribed of all visits with antibiotic prescriptions were the third-generation cephalosporins (34.9%), macrolides (24.3%), and the second-generation cephalosporins (23.3%).

Conclusions
In mainland China, the overall rate of antibacterial prescribing and the proportion of injection formulations prescribed in children under 5 years with URIs were at a low level, but still higher in underdeveloped regions and cities. Moreover, the overuse of the second and third generation cephalosporins, macrolides, remains a serious issue. Further efforts should be focused on reducing those non-first-line antibiotic prescribing and narrowing the gaps among regions and cities.
Decreased blood CD4+ T lymphocyte helps predict cognitive impairment in patients with amyotrophic lateral sclerosis
Authors: Yang Yuan , Pan Dengji , Gong Zhenxiang , Tang Jiahui , Li Zehui , Ding Fengfei , Liu Mao , Zhang Min 
Published: April 2021

Abstract
Background
ALS patients have changed peripheral immunity. It is unknown whether peripheral immunity is related to cognitive dysfunction in ALS patients.

Objective
To explore the relationship between the peripheral blood lymphocyte subsets and the cognitive status in ALS patients.

Methods
Among 81 ALS patients, we compared the demographic, clinical, and peripheral levels of total T lymphocyte, CD4+ T lymphocyte, CD8+ T lymphocyte, B lymphocyte, and NK cell between those with cognitive impairment (ALS-ci) and those without (ALS-nci). The cognitive status was evaluated via the Chinese version of the Edinburgh cognitive and behavioral screen (ECAS). Significant predictors of cognitive impairment in univariate logistic regression analysis were further examined using multivariate logistic regression analysis.

Results
39.5% of all ALS patients had cognitive impairment. The ALS-ci group had shorter education time, older age at both symptom onset and testing, longer disease duration, and lower levels of peripheral total, CD4+, and CD8+ T lymphocyte and B lymphocyte than the ALS-nci group. Frequency of behavioral impairment did not differ between the two groups. While parameters with significant differences identified by group comparison were also significant predictors of cognitive impairment in univariate logistic regression analysis except the level of B lymphocyte, only older age at testing, education time less than 9 years, and lower level of CD4+ T lymphocyte remained significant in multivariate logistic regression analysis. The predictive model combining these three parameters had an area under the receiver operating characteristic curve value of 0.842 with a sensitivity of 90.6% and a specificity of 67.3%.

Conclusion
In Chinese ALS patients, blood CD4+ T lymphocyte might help evaluate cognitive impairment along with age and education level.
Mothers and their children’s health (MATCH): a study protocol for a population‐based longitudinal cohort
Authors: Pirjani Reihaneh , Moini Ashraf , Heshmati Javad , Mardi-Mamaghani Azar , Esmaeili Mahnaz , Shafaatdoost Mehrnoosh , Maleki-Hajiagha Arezoo , Karimi Elham , Hossein-boroujerdi Mojgan , Shokri Fatemeh , Mosanezhad Zahra , Bajool Niloofar , Noori Matina , Hosseini Ladan , Persad Emma , Sepidarkish Mahdi 
Published: April 2021

Abstract
Background
The quality of prenatal care is critical for the prevention of adverse pregnancy outcomes. However, according to the World Health Organization (WHO), only 64 % of women worldwide have access to over four sessions of prenatal care throughout their pregnancy. Thus, studies that address factors affecting maternal and child health status before and after pregnancy are of immense importance. The primary aim of the mothers and their children’s health (MATCH) cohort study is to evaluate the effect of nutrition, sleep quality, and lifestyle on maternal and neonatal outcomes.

Methods
A prospective cohort of > 2500 pregnant women in the first trimester (before 12 weeks’ gestation) will be recruited at Arash Women’s Hospital in Tehran, Iran between February 2020 and August 2021. All eligible pregnant women will be followed from their first trimester of pregnancy until delivery at four time points and assessed through a series of in-person visits with interviewer-administered questionnaires and telephone interviews. Detailed data will be collected on maternal demographics, lifestyle, medical history, reproductive history, obstetric history, dietary intake, sleep pattern, blood specimens, and anthropometric measurements, alongside paternal demographics, lifestyle, and family history. The outcomes will include antenatal, peripartum, and postnatal maternal complications and infant growth and neurodevelopment.

Discussion
The results of the MATCH cohort study will support the development of contextual interventions that can enhance antenatal, peripartum, and postnatal status, neonatal outcomes, and longevity mother and child.
Bioinformatics analysis of the expression and role of microRNA-221-3p in head and neck squamous cell carcinoma
Authors: Zhou Ziyan , Wu Wenling , Li Jixi , Liu Chang , Xiao Zixi , Lai Qinqiao , Qin Rongxing , Shen Mingjun , Shi Shuo , Kang Min 
Published: April 2021

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC are still not clear. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC.

Methods
Tissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by RT-qPCR. Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology. Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC.

Results
We observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz. Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of miR-221-3p.

Conclusion
Based on bioinformatics analysis, our results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p may be an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC. Hopefully, additional work will validate its usefulness as a target for future clinical research.
Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling
Authors: Wang Fengjiao , Wang Lai , Qu Chao , Chen Lianyu , Geng Yawen , Cheng Chienshan , Yu Shulin , Wang Dan , Yang Lina , Meng Zhiqiang , Chen Zhen 
Published: April 2021

Abstract
Background
Kaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism.

Methods
PANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database.

Results
Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway.

Conclusions
Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.
Effects of lid debris debridement combined with meibomian gland expression on the ocular surface MMP-9 levels and clinical outcomes in moderate and severe meibomian gland dysfunction
Authors: Moon Su Young , Han Sol Ah , Kwon Hye Ji , Park So Young , Lee Jae Hyuck , Chung Ho Seok , Kim Jae Yong , Tchah Hungwon , Lee Hun 
Published: April 2021

Abstract
Background
To evaluate the effects of lid debris debridement and meibomian gland expression (MGX) on extracellular matrix metalloproteinase-9 (MMP-9) levels and clinical outcomes of moderate and severe MGD.

Methods
In this retrospective case series study, a total 48 eyes of 24 patients with moderate and severe MGD underwent one session of lid debris debridement using the BlephEx combined with MGX. We evaluated the tear film break-up time (TBUT), corneal and conjunctival fluorescein staining scores, Schirmer 1 test, biomicroscopic examination of lid margins and meibomian gland (MG), ocular surface disease index (OSDI) questionnaire score, and extracellular MMP-9 levels using a point-of-care MMP-9 immunoassay device before and 4 weeks after lid debris debridement and MGX. Linear mixed model and generalized estimating equations model were used to evaluate possible differences.

Results
There were significant improvements in the TBUT (P = 0.002), SICCA and Oxford staining scores (all P < 0.001), lid margin telangiectasia (P < 0.001 for upper and lower eyelids), lid thickness (P < 0.001 for upper and lower eyelids), MG orifice plugging (P < 0.001 for upper and lower eyelids), meibum color (P = 0.026 for upper eyelid, P < 0.001 for lower eyelid), meibum consistency (P < 0.001 for upper and lower eyelids), meibum grade (P < 0.001), MGD stage (P < 0.001), and OSDI score (P = 0.002). MMP-9 immunoassay positivity rate significantly decreased from 83.3 to 50.0% 4 weeks after treatment (P = 0.014).

Conclusions
In patients with moderate to severe MGD, lid debris debridement using the BlephEx combined with MGX improved clinical findings, subjective symptoms, meibomian gland function, along with ocular surface MMP-9 level. We hereby suggest lid debris debridement using BlephEx combined with MGX as an effective clinical strategy for treatment of moderate to severe MGD.
Transpedicular bi‐vertebrae wedge osteotomy in treatment of post‐tubercular spinal deformity: a retrospective study
Authors: Huang Yi , Hu Wenhao , Li Jing , Wang Tianhao , Liu Huawei , Zheng Guoquan , Zhang Xuesong , Wang Yan 
Published: April 2021

AbstractBackgroundIn the late stage of spinal tuberculosis, the bony destruction and vertebral collapse often leads to significant kyphosis, presenting clinically as a painful gibbus deformity, with increased instability, vertebral body translations and increased risk of neurologic involvement. Spinal osteotomy is thought to be suitable for most patients with severe rigid kyphosis. The aim of this study was to evaluate the efficacy of transpedicular bi-vertebrae osteotomy technique in the patients with Pott’s kyphosis and other post-tubercular spinal deformity.MethodsBetween January 2012 and December 2015, 18 patients with post-tubercular spinal deformity underwent the transpedicular bi-vertebrae wedge osteotomy, with a minimum follow up of 27.0 months. Preoperative and postoperative kyphotic angle, sagittal plane parameters (TK for thoracic deformity, TLK for thoracolumbar and LL for lumbar deformity) and sagittal vertical axis (SVA) were measured. Oswestry Disability Index (ODI), Visual analog scale (VAS) and modified American Spinal Injury Association grading (ASIA) of preoperative and final follow-up were documented and compared.ResultsThe average operation time was 305 minutes (range, 200–430 minutes) with a mean intraoperative blood loss of 425 mL (range, 200-700 mL). The kyphotic angles decreased from 80.3° (range, 28.5°-130.8°) preoperatively to 26.1° (range, 7.0°-63.3°) at the final follow-up (P<0.01). The mean VAS score was reduced from preoperative 5.2(range, 2-9) to 0.9(range, 0-2,P<0.01) and the ODI improved from 55.3% (range, 46%-76%) to 6.3% (range, 2%-18%,P<0.01). At final follow-up, there was radiographic evidence of solid fusion at the osteotomy site and fixed segments in all patients. Neurological function improved from ASIA scale D to E in 7 patients, C to D in 3 patients.ConclusionsOur results suggest that transpedicular bi-vertebrae wedge osteotomy is a safe and effective treatment option for post-tubercular spinal deformity. This technique achieves satisfying correction and fusion rates with adequate decompression of neurological elements.