bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model to predict cause‐specific mortality in patients with olfactory neuroblastoma: a competing risk analysis
Authors: Liu Lipin , Zhong Qiuzi , Zhao Ting , Chen Dazhi , Xu Yonggang , Li Gaofeng 
Published: June 2021

Abstract
Purpose
The main objective of this study was to evaluate the cumulative incidence of cause-specific mortality and other causes of mortality for patients with olfactory neuroblastoma (ONB). The secondary aim was to model the probability of cause-specific death and build a competing risk nomogram to predict cause-specific mortality for this disease.

Methods
Patients with ONB from 1975 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. We estimated the cumulative incidence function (CIF) for cause-specific mortality and other causes of mortality, and constructed the Fine and Gray’s proportional subdistribution hazard model, as well as a competing-risk nomogram based on Fine and Gray’s model, to predict the probability of cause-specific mortality for patients with ONB.

Results
After data selection, 826 cases were included for analysis. Five-year cumulative incidence of cause-specific mortality was 19.5% and cumulative incidence of other causes of mortality was 11.3%. Predictors of cause-specific mortality for ONB included tumor stage, surgery and chemotherapy. Age was most strongly predictive of other causes of mortality: patients aged > 60 years exhibited subdistribution hazard ratios of 1.063 (95 % confidence interval [CI] 1.05–1.08; p = 0.001). The competing risk nomogram for cause-specific mortality was well-calibrated, and had good discriminative ability (concordance index = 0.79).

Conclusions
We calculated the CIF of cause-specific mortality and other causes of mortality in patients with the rare malignancy ONB. We also built the first competing risk nomogram to provide useful individualized predictive information for patients with ONB.
Patient and hospital factors associated with 30-day readmissions after coronary artery bypass graft (CABG) surgery: a systematic review and meta-analysis
Authors: Shawon Md Shajedur Rahman , Odutola Michael , Falster Michael O. , Jorm Louisa R. 
Published: June 2021

Abstract
Background
Readmission after coronary artery bypass graft (CABG) surgery is associated with adverse outcomes and significant healthcare costs, and 30-day readmission rate is considered as a key indicator of the quality of care. This study aims to: quantify rates of readmission within 30 days of CABG surgery; explore the causes of readmissions; and investigate how patient- and hospital-level factors influence readmission.

Methods
We conducted systematic searches (until June 2020) of PubMed and Embase databases to retrieve observational studies that investigated readmission after CABG. Random effect meta-analysis was used to estimate rates and predictors of 30-day post-CABG readmission.

Results
In total, 53 studies meeting inclusion criteria were identified, including 8,937,457 CABG patients. The pooled 30-day readmission rate was 12.9% (95% CI: 11.3–14.4%). The most frequently reported underlying causes of 30-day readmissions were infection and sepsis (range: 6.9–28.6%), cardiac arrythmia (4.5–26.7%), congestive heart failure (5.8–15.7%), respiratory complications (1–20%) and pleural effusion (0.4–22.5%). Individual factors including age (OR per 10-year increase 1.12 [95% CI: 1.04–1.20]), female sex (OR 1.29 [1.25–1.34]), non-White race (OR 1.15 [1.10–1.21]), not having private insurance (OR 1.39 [1.27–1.51]) and various comorbidities were strongly associated with 30-day readmission rates, whereas associations with hospital factors including hospital CABG volume, surgeon CABG volume, hospital size, hospital quality and teaching status were inconsistent.

Conclusions
Nearly 1 in 8 CABG patients are readmitted within 30 days and the majority of these are readmitted for noncardiac causes. Readmission rates are strongly influenced by patients’ demographic and clinical characteristics, but not by broadly defined hospital characteristics.
Characteristics and possible mechanisms of 46, XY differences in sex development caused by novel compound variants in NR5A1 and MAP3K1
Authors: Cheng Yiping , Chen Jing , Zhou Xinli , Yang Jiangfei , Ji Yiming , Xu Chao 
Published: June 2021

Abstract
Background
Dozens of genes are involved in 46, XY differences in sex development (DSD). Notably, about 3/4 of patients cannot make a clear etiology diagnosis and single gene variant identified cannot fully explain the clinical heterogeneity of 46, XY DSD.

Materials and methods
We conducted a systematic clinical analysis of a 46, XY DSD patient, and applied whole-exome sequencing for the genetic analysis of this pedigree. The identified variants were analyzed by bioinformatic analysis and in vitro studies were performed in human embryonic kidney 293T (HEK-293T) cells which were transiently transfected with wild type or variant NR5A1 and MAP3K1 plasmid. Furthermore, protein production of SRY-box transcription factor 9 (SOX9) was analyzed in cell lysates.

Results
A novel NR5A1 variant (c.929A > C, p. His310Pro) and a rare MAP3K1 variant (c.2282T > C, p. Ile761Thr) were identified in the proband, whereas the proband's mother and sister who only carry rare MAP3K1 variant have remained phenotypically healthy to the present. These two variants were predicted to be pathogenic by bioinformatic analysis. In vitro, NR5A1 variant decreased the SOX9 production by 82.11% compared to wild type NR5A1, while MAP3K1 variant had little effect on the SOX9 production compared to wild type MAP3K1. Compared to wild type NR5A1 transfection, the SOX9 production of cells transfected with both wild type plasmids decreased by about 17.40%. Compared to variant NR5A1 transfection, the SOX9 production of cells transfected with both variant plasmids increased by the 36.64%.

Conclusions
Our findings suggested the novel compound variants of NR5A1 and MAP3K1 can alter the expression of SOX9 and ultimately lead to abnormality of sex development.
Outcome of L-DEP regimen for treatment of pediatric chronic active Epstein–Barr virus infection
Authors: Ma Honghao , Zhang Liping , Wei Ang , Yang Jun , Wang Dong , Zhang Qing , Zhao Yunze , Chen Sitong , Lian Hongyun , Zhang Li , Zhou Chunju , Qin Maoquan , Li Zhigang , Wang Tianyou , Zhang Rui 
Published: June 2021

Abstract
Purpose
We intended to investigate the clinical features of paediatric patients with chronic active Epstein–Barr virus infection (CAEBV) and to examine the effectiveness of the L-DEP regimen before haematopoietic stem cell transplantation (HSCT).

Methods
A retrospective analysis was performed on 35 patients with CAEBV at Beijing Children’s Hospital from January 2016 to January 2020. The efficacy and adverse events of the L-DEP regimen were evaluated.

Results
The median age of the 35 patients was 7.0 years old (range 2.5–17.5 years). Twenty-eight patients achieved a clinical response (80.0%, 22 in clinical CR, 6 in clinical PR) after L-DEP. In terms of virological response, 7 patients (20%) were assessed as having virological CR, and 23 patients (65.7%) had virological PR. Finally, 29 patients underwent allo-HSCT. The median survival time was 18 months (2–50 months). The 3-year overall survival rates in patients treated with chemotherapy only (n = 6) and chemotherapy followed by HSCT (n = 25) were 33.3% and 75.4%, respectively. After L-DEP 1st treatment and L-DEP 2nd treatment, the EBV-DNA loads in blood and plasma were significantly reduced compared with those before chemotherapy (median: 4.29 × 105 copies/ml vs. 1.84 × 106 copies/ml, Mann–Whitney U: P = 0.0004; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, Mann–Whitney U; P = 0.003; 2.27 × 105 copies/ml vs. 1.84 × 106 copies/ml, P = 0.0001; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, P = 0.003). Compared with the liver and spleen size before chemotherapy, the size of the liver and spleen shrank significantly after L-DEP 2nd (median 3.8 cm vs. 1.9 cm, P = 0.003; 3.8 cm vs. 0 cm, P < 0.008). In addition, after L-DEP treatment, there was no difference in the clinical or virological response rate regardless of HLH status (clinical response: 77.3% vs. 84.6%, P = 0.689; virological response: 90.9% vs. 76.9%, P = 0.337).

Conclusion
The L-DEP regimen is an effective therapy in CAEBV for bridging to allo-HSCT.
CircPVT1 promotes proliferation of lung squamous cell carcinoma by binding to miR-30d/e
Authors: Shi Jie , Lv Xin , Zeng Lizhong , Li Wei , Zhong Yujie , Yuan Jingyan , Deng Shanshan , Liu Boxuan , Yuan Bo , Chen Yang , Ming Zongjuan , Yang Xia , Fang Ping , Yang Shuanying , Chen Guoan 
Published: June 2021

Abstract
Background
Circular RNAs (circRNAs) are a new type of extensive non-coding RNAs that regulate the activation and progression of different human diseases, including cancer. However, information on the underlying mechanisms and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remains scant.

Methods
The expression profile of RNAs in 8 LUSC tissues, and 9 healthy lung tissues were assayed using RNA sequencing (RNA-seq) techniques. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to profile the expression of circPVT1 and its relationship with the prognosis of LUSC, i.e., survival analysis. Moreover, in vitro and in vivo experiments were performed to evaluate the impacts of circPVT1 on the growth of tumors. RNA pull-down tests, mass spectrometry, dual-luciferase reporter assessment, and RNA immune-precipitation tests were further conducted to interrogate the cross-talk between circPVT1, HuR, or miR-30d/e in LUSC.

Results
Our data showed that circPVT1 was upregulated in LUSC tissues, serum, and cell lines. LUSC patients with higher circPVT1 expression exhibited shorter survival rates. The in vivo and in vitro data revealed that circPVT1 promotes the proliferation of LUSC cells. Additionally, mechanistic analysis showed that HuR regulated circPVT1. On the other hand, circPVT1 acted as a competing endogenous RNA (ceRNA) of miR-30d and miR-30e in alleviating the suppressive influences of miR-30d and miR-30e on its target cyclin F (CCNF).

Conclusion
CircPVT1 promotes LUSC progression via HuR/circPVT1/miR-30d and miR-30e/CCNF cascade. Also, it acts as a novel diagnostic biomarker or treatment target of individuals diagnosed with LUSC.
Successful experimental infant baboon model for childhood cryptosporidiosis studies
Authors: Jillani Ngalla E. , Nyachieo Atunga , Chai Daniel C. , Nyariki James Nyabuga 
Published: June 2021

Abstract
Background
Cryptosporidiosis causes high morbidity and mortality in children under 2 years of age globally. The lack of an appropriate animal model that mimics the pathogenesis of disease in humans has hampered the development and testing of potential therapeutic options. This study aimed to develop and validate an infant baboon infection model of cryptosporidiosis.

Methods
Eighteen immunocompetent weaned infant baboons aged 12 to 16 months were used. The animals were n = 3 controls and three experimental groups of n = 5 animals each inoculated with Cryptosporidium parvum oocysts as follows: group 1: 2 × 104, group 2: 2 × 105, group 3: 2 × 106 followed by daily fecal sampling for oocyst evaluation. Blood sampling for immunological assay was done on the day of infection and weekly thereafter until the end of the experiment, followed by necropsy and histopathology. Statistical analysis was performed using R, SPSS, and GraphPad Prism software. Analysis of variance (ANOVA) and Bonferroni post hoc tests were used for comparison of the means, with p < 0.05 considered as a significant difference. Correlation coefficient and probit analysis were also performed.

Results
In all experimental animals but not controls, the onset of oocyst shedding occurred between days 2 and 4, with the highest oocyst shedding occurring between days 6 and 28. Histological analysis revealed parasite establishment only in infected animals. Levels of cytokines (TNF-α, IFN-γ, and IL-10) increased significantly in experimental groups compared to controls.

Conclusion
For developing a reproducible infant baboon model, 2 × 104 oocysts were an effective minimum quantifiable experimental infection dose.

Graphic abstract
Poor vector competence of the human flea, Pulex irritans, to transmit Yersinia pestis
Authors: Miarinjara Adélaïde , Bland David M. , Belthoff James R. , Hinnebusch B. Joseph 
Published: June 2021

Abstract
Background
The human flea, Pulex irritans, is widespread globally and has a long association with humans, one of its principal hosts. Its role in plague transmission is still under discussion, although its high prevalence in plague-endemic regions and the presence of infected fleas of this species during plague outbreaks has led to proposals that it has been a significant vector in human-to-human transmission in some historical and present-day epidemiologic situations. However, based on a limited number of studies, P. irritans is considered to be a poor vector and receives very little attention from public health policymakers. In this study we examined the vector competence of P. irritans collected from foxes and owls in the western United States, using a standard protocol and artificial infection system.

Methods
Wild-caught fleas were maintained in the laboratory and infected by allowing them to feed on human or rat blood containing 2 × 108 to 1 × 109Y. pestis/ml. The fleas were then monitored periodically for infection rate and bacterial load, mortality, feeding rate, bacterial biofilm formation in the foregut (proventricular blockage), and ability to transmit Y. pestis after their single infectious blood meal.

Results
P. irritans were susceptible to infection, with more than 30% maintaining high bacterial loads for up to 20 days. Transmission during this time was infrequent and inefficient, however. Consistent with previous studies, a low level of early-phase transmission (3 days after the infectious blood meal) was detected in some trials. Transmission at later time points was also sporadic, and the incidence of proventricular blockage, required for this mode of transmission, was low in fleas infected using rat blood and never occurred in fleas infected using human blood. The highest level of blockage and transmission was seen in fleas infected using rat blood and allowed to feed intermittently rather than daily, indicating that host blood and feeding frequency influence vector competence.

Conclusions
Our results affirm the reputation of P. irritans as a feeble vector compared to rodent flea species examined similarly, and its vector competence may be lower when infected by feeding on bacteremic human blood.

Graphic abstract
Comparison of mitochondrial genome and development of specific PCR primers for identifying two scuticociliates, Pseudocohnilembus persalinus and Uronema marinum
Authors: Huang Yu-Xi , Wang Sen , Gao Yan-Qi , Chen Jie-Hu , Wang Xiu-Li , Li Rui-Jun 
Published: June 2021

AbstractBackgroundPseudocohnilembus persalinusandUronema marinum(Ciliophora, Scuticociliatia), as parasitic scuticociliatid ciliates, were isolated fromScophthalmus maximusandTakifugu rubripes, respectively, in our previous studies. These ciliates are morphologically very similar; hence, it is difficult to identify specific scuticociliate species using traditional classification methods for performing taxonomic research and disease control studies.MethodsWe annotated the mitochondrial genomes of these two scuticociliates on the basis of previous sequencing, including analyses of nucleotide composition, codon usage, Ka/Ks, and p-distance. We also compared the nucleotide and amino acid similarity of the mitochondrial genomes ofP. persalinus,U. marinum, and other 12 related ciliates, and a phylogenetic tree was constructed using 16 common genes. We chose thenad4andnad7genes to design specific PCR primers for identification.ResultsP. persalinusandU. marinumwere found to have a close evolutionary relationship. Although codon preferences were similar, differences were observed in the usage of codons such as CGA, CGC, and GTC. Both Ka/Ks and p-distance were less than 1. Except foryejR,ymf57,ymf67, andymf75, the amino acid sequence similarity betweenP. persalinusandU. marinumwas greater than 50%.ConclusionsThe mitochondrial genomes ofP. persalinusandU. marinumwere thoroughly compared to provide a reference for disease prevention and control. The specific PCR primers enabled us to identifyP. persalinusandU. marinumrapidly and accurately at the molecular level, thus providing a basis for classification and identification.Graphic abstract
Conservation and diversity of the eukaryotic SAGA coactivator complex across kingdoms
Authors: Chen Ying-Jiun C. , Dent Sharon Y. R. 
Published: June 2021

AbstractThe SAGA complex is an evolutionarily conserved transcriptional coactivator that regulates gene expression through its histone acetyltransferase and deubiquitylase activities, recognition of specific histone modifications, and interactions with transcription factors. Multiple lines of evidence indicate the existence of distinct variants of SAGA among organisms as well as within a species, permitting diverse functions to dynamically regulate cellular pathways. Our co-expression analysis of genes encoding human SAGA components showed enrichment in reproductive organs, brain tissues and the skeletal muscle, which corresponds to their established roles in developmental programs, emerging roles in neurodegenerative diseases, and understudied functions in specific cell types. SAGA subunits modulate growth, development and response to various stresses from yeast to plants and metazoans. In metazoans, SAGA further participates in the regulation of differentiation and maturation of both innate and adaptive immune cells, and is associated with initiation and progression of diseases including a broad range of cancers. The evolutionary conservation of SAGA highlights its indispensable role in eukaryotic life, thus deciphering the mechanisms of action of SAGA is key to understanding fundamental biological processes throughout evolution. To illuminate the diversity and conservation of this essential complex, here we discuss variations in composition, essentiality and co-expression of component genes, and its prominent functions across Fungi, Plantae and Animalia kingdoms.
STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease
Authors: Yu Ya-Li , Chen Meng , Zhu Hua , Zhuo Ming-Xing , Chen Ping , Mao Yu-Juan , Li Lian-Yun , Zhao Qiu , Wu Min , Ye Mei 
Published: June 2021

Abstract
Background
The aetiology of inflammatory bowel disease (IBD) is related to genetics and epigenetics. Epigenetic regulation of the pathogenesis of IBD has not been well defined. Here, we investigated the role of H3K27ac events in the pathogenesis of IBD. Based on previous ChIP-seq and RNA-seq assays, we studied signal transducer and activator of transcription 1 (STAT1) as a transcription factor (TF) and investigated whether the STAT1–EP300–H3K27ac axis contributes to the development of IBD. We performed ChIP-PCR to investigate the interaction between STAT1 and H3K27ac, and co-IP assays were performed to investigate the crosstalk between STAT1 and EP300.

Results
Lymphocyte cytosolic protein 2 (LCP2) and TNF-α‐inducible protein 2 (TNFAIP2) are target genes of STAT1. p-STAT1 binds to the enhancer loci of the two genes where H3K27ac is enriched, and EP300 subsequently binds to regulate their expression. In mice with dextran sulfate sodium (DSS)-induced acute colitis, an EP300 inhibitor significantly inhibited colitis.

Conclusions
p-STAT1 and EP300 promote TNFAIP2 and LCP2 expression through an increase in H3K27ac enrichment on their enhancers and contribute to the pathogenesis of chronic inflammation.

Graphic abstract
T-staging pulmonary oncology from radiological reports using natural language processing: translating into a multi-language setting
Authors: Nobel J. Martijn , Puts Sander , Weiss Jakob , Aerts Hugo J. W. L. , Mak Raymond H. , Robben Simon G. F. , Dekker André L. A. J. 
Published: June 2021

Abstract
Background
In the era of datafication, it is important that medical data are accurate and structured for multiple applications. Especially data for oncological staging need to be accurate to stage and treat a patient, as well as population-level surveillance and outcome assessment. To support data extraction from free-text radiological reports, Dutch natural language processing (NLP) algorithm was built to quantify T-stage of pulmonary tumors according to the tumor node metastasis (TNM) classification. This structuring tool was translated and validated on English radiological free-text reports. A rule-based algorithm to classify T-stage was trained and validated on, respectively, 200 and 225 English free-text radiological reports from diagnostic computed tomography (CT) obtained for staging of patients with lung cancer. The automated T-stage extracted by the algorithm from the report was compared to manual staging. A graphical user interface was built for training purposes to visualize the results of the algorithm by highlighting the extracted concepts and its modifying context.

Results
Accuracy of the T-stage classifier was 0.89 in the validation set, 0.84 when considering the T-substages, and 0.76 when only considering tumor size. Results were comparable with the Dutch results (respectively, 0.88, 0.89 and 0.79). Most errors were made due to ambiguity issues that could not be solved by the rule-based nature of the algorithm.

Conclusions
NLP can be successfully applied for staging lung cancer from free-text radiological reports in different languages. Focused introduction of machine learning should be introduced in a hybrid approach to improve performance.
CT appearances, patterns of progression, and follow-up of COVID-19: evaluation on thin-section CT
Authors: Guan Chun-Shuang , Lv Zhi-Bin , Li Jing-Jing , Du Yan-Ni , Chen Hui , Cui Tao , Guo Ning , Chen Bu-Dong , Xie Ru-Ming 
Published: June 2021

Abstract
Background
To retrospectively analyze CT appearances and progression pattern of COVID-19 during hospitalization, and analyze imaging findings of follow-up on thin-section CT.

Methods
CT findings of 69 patients with COVID-19 were evaluated on initial CT, peak CT, and pre-discharge CT. CT pattern were divided into four types on CT progression. Lesion percentage of pulmonary lobe (lobe score) was graded. Correlation analysis was made between scores and intervals. 53 patients were followed up by CT.

Results
Among 69 patients, 33.3% exhibited improvement pattern, 65.2% peak pattern, 1.5% deterioration pattern, and 0% fluctuation pattern. The lobe scores were positively correlated with most of intervals. It was more common to observe consolidation, pleural thickening and pleural effusion on the peak CT, and irregular line and reticulation on pre-discharge CT. The peak-initial interval were shortened when the initial CT with consolidation and pleural thickening. The intervals were extended when the irregular lines appeared on peak CT and reticulation on pre-discharge CT. Among 53 follow-up patients, 37.7% showed normal chest CT, and 62.3% showed viral pneumonia remained that mainly included GGO (100.0%) and irregular lines (33.3%).

Conclusions
COVID-19 displayed different appearances on CT as progressing. The peak pattern was the most common progression pattern. The CT appearances showed closely related to the intervals. The COVID-19 pneumonia can be remained or completely absorbed on CT with follow-up.