bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Manual Immature to Total Neutrophil (I/T) Ratio and Automated Immature Granulocyte Count (IGC) and Percentage (IG%) in the Early Diagnosis of Neonatal Sepsis
Authors: Jayasekara Nalika , Kulathilake Chandima , Wijesekara Saraji , Wijesiriwardena Indira 
Published: January 2021

Abstract
Background: The diagnosis of neonatal sepsis is challenging due to non-specific and subtle clinical features, low sensitivity and delay in routine laboratory tests. Current study was conducted to evaluate the role of manual immature/total (I/T) neutrophil ratio and automated immature granulocyte count (IGC) and immature granulocyte percentage (IG%) in the diagnosis of neonatal sepsis. Materials and Methods: An analytical cross-sectional study was done during a period of 6 months with a sample of 55 neonates admitted to Colombo South Teaching Hospital, Sri Lanka. A combination of clinical and laboratory parameters including full blood count, C-reactive protein and blood culture were used to identify the neonates with probable sepsis. The population was subcategorized into five (5) groups and manual immature/total neutrophil (I/T) ratio, immature granulocyte count (IGC) and immature granulocyte%(IG%) were done in each neonate. Results: The sensitivity of manual I/T ratio was 93.75% and negative predictive value (NPV) was 95.24%. The sensitivity for lower cut off values, IGC of 0.03x103/µL and IG% of 0.5% was 80% and 73.33% respectively. The NPV for above cut-off values were 25% and 0.5% respectively. The NPV was improved with higher cut-off values with 70.90% for IGC 0.3 and 70.59% for IG 3%, but sensitivity remained low with 40% and 33.33% respectively.Conclusion: Manual I/T ratio remains as a useful diagnostic tool in diagnosing and excluding neonatal sepsis with a very good sensitivity and NPV. However, further studies and well defined reference intervals are required in automated IGC and IG%.
Bioinformatics Analysis the Expression Characteristics of RNA m6A Methylation Regulator in Breast Cancer Progression
Authors: Zhao Ping , Huang Xinwei , Wu Anhao , Yang Xin , Fu Yang , Quan Yuhang , Li Zhen , Tang Qi , Zhang Ji , Wang Maohua 
Published: January 2021

Abstract
Background: RNA m6A methylation regulator has been shown to play an important regulatory role in tumorigenesis and progression. However, the role and characteristics of RNA m6A methylation in breast cancer are not yet clear. Objective: To analyze the effect of the expression pattern of M6A methylation factor on the progression of breast cancer by bioinformatics.Results: This study uses bioinformatics to analyze three data sets of TCGA-BRCA, GSE96058 and GSE25066. According to the expression level of m6A-related genes, breast cancer samples are divided into 4 subtypes: quiescent, m6A-methylation, protein-binding, and mixed. The results of R-survival analysis showed that the survival of breast cancer samples of the four subtypes was significantly different. The analysis of breast cancer gene expression features showed that there are significant differences in the number of exon skip among the four subtypes. For tumor driver genes, the degree of TP53 mutation and copy number loss are the most in the protein-binding subtype. Among DNA damage repair genes, the copy number of RAD54B in the protein binding subtype is significantly increased, while other DNA damage repair-related genes have fewer mutations and copy number deletions are common. The effect of m6A methylation on the proportion of infiltrated immune cells indicates that Macrophages M0 and Mast cells resting are significantly different in the four m6A subgroups, and are related to patient prognosis. The number of sensitive samples of chemotherapeutics (taxane anthracyclines) is the lowest in the quiescent subtype. In addition, the highest tumor stemness index in breast cancer samples is the protein-bound type, and the lowest is the m6A methylated type. Conclusion: The results of our analysis suggest that the reduced expression level of m6A methylation writer gene and the high expression of m6A reader protein in the four methylation subtypes of breast cancer are key to the progression of breast cancer.
A Computer-Aided Diagnosis System of Fetal Nucleated Red Blood Cell With Convolutional Neural Network
Authors: Sun Chao , Wang Ruijie , Zhao Lanbo , Han Lu , Ma Sijia , Liang Dongxin , Wang Lei , Tuo Xiaoqian , Zhang Yu , Zhong Dexing , Li Qiling 
Published: January 2021

Abstract
Background: The rapid recognition of fetal nucleated red blood cells (fNRBCs) present considerable challenges.Objective: To establish a computer-aided diagnosis system (CAD) for rapid recognition of fNRBCs by a convolutional neural network (CNN). Methods: We adopted density gradient centrifugation and magnetic-activated cell sorting to extract fNRBCs from umbilical cord blood samples. A cell-block method was used to embed fNRBCs for routine formalin-fixed paraffin sectioning and hematoxylin-eosin stains. Then we proposed a CAD-based on CNN to automatically learn discriminative features and recognize fNRBCs. Region of interest 1 extraction methods were used to automatically segment individual cells in cell slices. The discriminant information from ROIs was encoded into a feature vector. The prediction network provided a pathological diagnosis. Results: Totally, 4760 pictures of fNRBCs from 260 cell-slides of 4 umbilical cord blood samples were collected. On the premise of 100% accuracy in the training set (3720 pictures) the sensitivity, specificity, and accuracy of cellular intelligent recognition were 96.5%, 100%, and 98.5% in the test set (1040 pictures).Conclusion: We present a CAD system for effective and accurate fNRBCs recognition based on CNN.
LY96&nbsp;Upregulation Promotes Kidney Renal Clear Cell Carcinoma (KIRC)
Authors: Xu Ji-li , Guo Yong 
Published: January 2021

Abstract
Background: LY96 has been reported to be relevant with kidney inflammatory injury but the function of this gene in kidney renal clear cell carcinoma (KIRC) remains unknown.Methods: Various online tools were applied to analyze the roles of LY96 in KIRC using data from the Cancer Genome Atlas. Differential LY96 expression and overall survival (OS) based on different expression levels were analyzed through Oncomine and GEPIA tools. The alterations, related genes, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways of LY96 were explored via cBioPortal and STRING database. LinkedOmics and Cistrome DB Toolkit were utilized to identify targets of kinase, miRNAs, and transcription factors. The relationship between LY96 and some associated genes or regulatory factors was displayed via GeneMANIA and TIMER tool. TISIDB revealed correlations between LY96 expression and immune-associated factors in the tumor microenvironment. Results: High LY96 expression level was observed in KIRC and associated with poor prognosis and diverse clinical characteristics. LY96 often amplified in KIRC and was mostly linked to the inflammatory response. Several highly correlated genes, kinase targets, transcription factors, and DNA methyltransferase that may interact with LY96 were all identified. Our study also demonstrated that various immune-related factors were relevant to LY96 in KIRC. Conclusions: Our study has shown the complex relationships between LY96 and KIRC from diverse angles. High LY96 expression had an adverse effect on the prognosis of KIRC. To find effective demethylation agents and transcription factors inhibitors targeting LY96 may have beneficial effects on the survival of KIRC patients.
Lung Recruitment Improves the Efficacy of Intubation-Surfactant-Extubation Treatment for Respiratory Distress Syndrome in Preterm Neonates, A Randomized Controlled Trial
Authors: Yang Yong , Yan Wenkang , Ruan MinYi , Zhang Lan , Su Jinzhen , Deng Haohui , Li Minxu 
Published: January 2021

Abstract
Background: Lung recruitment is a maneuver in preterm neonates at birth, which may decrease the length of intubation. This study aimed to compare the therapeutic efficacy of lung recruitment plus intubation-surfactant-extubation (INSURE) procedure and INSURE alone for the preterm neonates with respiratory distress syndrome.Methods: A total of 184 preterm neonates with respiratory distress syndrome from 2017 to 2019 were enrolled and randomized into the lung recruitment group receiving lung recruitment (25 cm H2O for 15 seconds) plus INSURE and the control group receiving INSURE only. The primary outcome was the need for mechanical ventilation (MV) within 72 h after extubation. The secondary outcomes include the duration of intubation, noninvasive ventilation, total oxygen therapy, hospitalization, and other complications.Results: Compared to the control group, the lung recruitment group had a significantly lower proportion of preterm neonates need for MV within 72 h after extubation (23% vs. 38%, P=0.025) and pulmonary surfactant administration, as well as shorter the MV duration. Multivariate logistic regression analysis demonstrated that the control group had a 2.17-time higher risk for need for MV than the lung recruitment group (OR: 2.17, 95% CI: 1.13-4.18; P=0.021). In the mothers with hypertension, the infants presented a 2.41-time higher risk for requiring MV as compared with those of mothers with normotension (OR: 2.41, 95% CI: 1.15-5.05; P=0.020). Conclusion: These data suggested that lung recruitment plus INSURE can reduce the need for MV within 72 hours after extubation without increasing the incidence of complications and mortality.
The Impact of the Coronavirus Pandemic on Patients With Acute Proximal Femoral Fracture: a Retrospective, Observational, Cohort Study
Authors: Tong Anna , Singh Amit , Pinder Charlotte , Onafowokan Oluwatobi , Toh Wei Hann , Asthwanth Ramesh , Rogers Sophie , Gandavaram Srikanth , Sinclair Victoria 
Published: January 2021

Abstract
• Background – During the initial peak of the COVID-19 pandemic in the United Kingdom (UK) admissions related to acute proximal femoral fracture (APFF) remained consistent.• Aims – This aim of this research is to demonstrate the impact of the COVID-19 pandemic on this cohort of high-risk patients and provide revenues for improvement in their care as we globally progress through further peaks of viral transmission and illness.• Methods– Retrospective, observational, cohort study of 112 patients with APFF; sustained during the first peak of the pandemic (1st March – 15th May, 2020). Following ethical approval, data was collected from electronic records. Included patients were those who had been admitted to one of two district general hospitals in Northwest England. Only patients with APFF were included – chronic, peri-prosthetic, femoral shaft and open fractures were excluded. Patients were split into two groups: COVID-positive (N = 17) and COVID-negative (N = 95) with the primary outcome measure being 30-day mortality.• Results – 17.9% overall mortality (29.4% for COVID-positive and 15.7% for COVID-negative). The odds ratio for mortality was 2.2 in the COVID-positive group compared to the COVID-negative group (95% confidence level; 0.68–7.23).• Conclusions – Patients with APFF suffered increased mortality during the initial peak of the COVID-19 pandemic. However, increased mortality in COVID-positive patients, compared to the COVID-negative patients, was not statistically significant. Increased mortality in COVID-negative patients may have been due to other pandemic related factors including: undiagnosed COVID-19; patient demographics and the effects of changes to the service provision structure of the orthopaedic department during this time. Moving forward, as the global fight against COVID-19 continues, we provide the below recommendations as suggested revenues to improve 30-day mortality for these patients during pandemic times:• repeated COVID-19 testing for all APFF patients;• strict separation of COVID-suspected, COVID-positive, and COVID-negative patients;• preservation of acute trauma services, including protected theatre time; and• maintenance of experienced orthopaedic teams on wards throughout periods of re-deployment.Further research with larger sample sizes is needed to assess the national and international applicability of these recommendations.
Effect of Sodium-Glucose Cotransporter Type 2 Inhibitors on Clinical Outcomes in Patients With Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials
Authors: Zheng Caiyun , Lin Meimei , Chen Yan , Xu Haiting , Yan Lingqun , Dai Hengfen 
Published: January 2021

Abstract
BackgroundControlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2s) are beneficial to the mortality of patients with heart failure (HF). However, it is unclear whether SGLT-2s can benefit patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the clinical benefits of SGLT-2s in cardiovascular patients with or without diabetes.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2s in patients with cardiovascular disease with or without diabetes. Primary outcomes were all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure. Secondary outcomes were major adverse events from cardiovascular, metabolic, renal, and infectious diseases. The effects of SGLT-2s were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality.ResultsWe identified 10 randomised controlled trials (24500 patients in the SGLT-2 group and 17960 patients in the placebo group). Meta-analysis showed that SGLT-2 treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.80–0.91; P < 0.00001; I2 = 11%; cardiovascular mortality RR: 0.85; 95% CI: 0.79–0.92; P < 0.0001; I2 = 35%; HHF RR: 0.69; 95% CI: 0.64–0.81; P < 0.00001; I2 = 0%). In patients with heart failure, mortality and HHF after SGLT-2 treatment for heart failure with reduced ejection fraction were significantly reduced, whereas heart failure with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2s induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher. ConclusionsIn this exploratory analysis, SGLT-2s had significant clinical effects in the treatment of patients with cardiovascular disease and had significant benefits in terms of renal function and myocardial infarction, but were associated with increased risk of infection, ketoacidosis, amputation, and volume depletion.
Mental Health and Resilience among Eritrean Refugees at Arrival and One-Year Post-Registration in Switzerland: A Cohort Study
Authors: Chernet Afona , Probst-Hensch Nicole , Sydow Véronique , Paris Daniel Henry , Labhardt Niklaus Daniel 
Published: January 2021

Abstract
Objective:Eritrea tops the list of origin of asylum seekers in Switzerland. On their journey through the desert and across the Mediterranean Sea, refugees may be exposed to traumatizing experiences. The aim of this study is to assess the mental health status of Eritrean migrants in Switzerland upon arrival and one-year post-arrival, using standardized mental health screening tools. Results:At baseline, 107 refugees (11.2% female, median age 25) were interviewed: 52 (48.6%) screened positive for PTSD (score ≥30), 10.3% for anxiety (≥10) and 15.0% for depression (≥10); 17.8% scored as risk/hazardous drinkers (≥8). The majority (94.4%) had a high resilience score (≥65). For one-year follow-up, 48 asylum seekers could be reached. In interviews 18 (38%) of these reported imprisonment in a transit country and 28 (58%) that they had witnessed the death of a close person along the migration route. At the one year assessment, rates of risky/hazardous alcohol use remained unchanged, rates of positive PTSD screening tended to be lower (50.0% (24/48) at baseline vs 25.0% (12/48) at follow-up), as were rates of positive screening for anxiety (8.3% vs 4.2%) and depression (14.6 vs 6.3%).
WITHDRAWN: Long-term Complications After Stent Assist Coiling Dependent on Clopidogrel Response
Authors: Shoda Kenji , Enomoto Yukiko , Egashira Yusuke , Kinoshita Takamasa , Mizutani Daisuke , Iwama Toru 
Published: January 2021

Abstract
BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary for stent assisted coiling. However, long term use of DAPT has a potential risk of hemorrhagic events. We aimed to examine the relationship between clopidogrel reactivity and complications.METHODS: Patients who underwent stent assisted coiling for unruptured aneurysms and received periprocedural DAPT in our institution between August 2011 to March 2020 were included. Platelet reactivity for clopidogrel was measured by VerifyNow assay system, and we defined the cut off value of P2Y12 Reaction Units (PRU) at 208, and classified patients as hypo-responders (PRU≧208) or responders (PRU＜208). The rates of hemorrhagic and thrombotic events within 30 days (acute phase) and 30 days after the procedure (delayed phase) were compared between the two groups. Furthermore, changes in hemoglobin levels were measured before and after the procedure and at chronic stages (1 to 6 months thereafter).RESULTS: From 62 patients included in this study, 36 patients were hypo-responders and 26 patients were responders. Hemorrhagic events occurred 7.7% only in responders in the acute phase (p = 0.17), and 2.78% in hypo-responders and 23.1% in responders in the delayed phase (p = 0.02). Changes in hemoglobin levels before and after the procedure were 1.21 g/dl in hypo-responders and 1.92 g/dl in responders (p = 0.02) while before the procedure and chronic stages they were 0.39g/dl in hypo-responders and 1.41 g/dl in responders (p < 0.01). Thrombotic events were not significantly different between the two groups.CONCLUSION: Long term use of DAPT after stent assisted coiling is related to hemorrhagic events in the delayed phase. Preventing for hemorrhagic events, the duration of DAPT should be carefully considered in clopidogrel responders.
Rare manifestations and malignancies in tuberous sclerosis complex: Findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
Authors: Sauter Matthias , Belousova Elena , Benedik Mirjana P , Carter Tom , Cottin Vincent , Curatolo Paolo , Dahlin Maria , D´Amato Lisa , d'Augères Guillaume B. , de Vries Petrus J , Ferreira Jose C , Feucht Martha , Fladrowski Carla , Hertzberg Christoph , Jozwiak Sergiusz , Lawson John A , Macaya Alfons , Marques Ruben , Nabbout Rima , O’Callaghan Finbar , Qin Jiong , Sander Valentin , Shah Seema , Takahashi Yukitoshi , Touraine Renaud , Youroukos Sotiris , Zonnenberg Bernard , Jansen Anna , Kingswood John C 
Published: January 2021

Abstract
Background
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disorder caused by pathogenic mutations in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients.
Methods
TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2).
Results
Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.23% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%).
Conclusion
Rare manifestations collectively were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.
Diagnosis, treatment of Type Ⅰ autoimmune pancreatitis and management of relapse and side effects after steroid treatment in China
Authors: Tang Neng , Dou Xiao-lin , He Qun , Gong Xue-jun , Zhou Jun , Liu Guo-dong , You Xing , Ning Cai-hong , Ou Zheng-lin , Ke Mu-jing , Yi Xiao-ping , Ji Lian-dong 
Published: January 2021

Abstract
Background: Type Ⅰ autoimmune pancreatitis (AIP) have a dramatic response to steroid therapy, but the relapse rates (RRs) is very high, and the side effects of steroid therapy are inevitable. However, the management of relapse and side effects of steroid therapy have been poorly investigated and no series have been reported previously, so this article focuses on the management of relapse and side effects. Methods: A single-centre, retrospective, cohort study of the type Ⅰ AIP patients admitted to Xiangya Hospital Central South University from September 2008 to September 2019. Collection and retrospectively analyzed the clinicopathologic data and outcomes of type Ⅰ AIP patients. Results: 82 patients with type Ⅰ AIP were included. The ratio of male with female was 2.73: 1 with median age of onset of 52 years old. 73.2% were histologically confirmed, 62.2% were showed other organ involvement (OOI). 78.0% treated by medications: 40 cases (62.5%) prednisolone, 24 cases (37.5%) prednisolone plus cyclophosphamide. The effective rate of prednisolone and prednisolone plus cyclophosphamide was no significant difference (37/40 vs 22/24, P = 0.904). The RRs of prednisolone and prednisolone plus cyclophosphamide after remission have no significant difference (14/40 vs 7/24, P = 0.630). Increasing the dosage of prednisolone, the effective rate of the prednisolone treatment and prednisolone plus cyclophosphamide treatment relapsed patients were 78.57% and 71.43%, respectively. The side effects were diabetes mellitus (DM) in 12.5%; central obesity in 15.6%; hyperlipidemia in 18.8%; gastric ulcer in 6.3%; osteoporosis in 9.4%; bone fracture in 1.6%. For those side effects patients performed low dose prednisolone and expectant treatment have a ideal results. Conclusions: There was no significant difference between prednisolone and prednisolone plus cyclophosphamide in the treatment of type Ⅰ AIP. Increasing the dose of prednisolone can effectively treat relapsed patients. Low dose steroid and expectant treatment should be performed when side effects arised.