bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of differentially expressed genes at the single-cell level and prognosis prediction through bulk RNA sequencing data in breast cancer
Authors: Chen Hanghang , Tian Tian , Luo Haihua , Jiang Yong 
Published: September 2022

Background: The invention and development of single-cell technologies have contributed a lot to the understanding of tumor heterogeneity. The objective of this research was to investigate the differentially expressed genes (DEGs) between normal and tumor cells at the single-cell level and explore the clinical application of these genes with bulk RNA-sequencing data in breast cancer.Methods: We collected single-cell, bulk RNA sequencing (RNA-seq) and microarray data from two public databases. Through single-cell analysis of 23,909 mammary gland cells from seven healthy donors and 33,138 tumor cells from seven breast cancer patients, cell type-specific DEGs between normal and tumor cells were identified. With these genes and the bulk RNA-seq data, we developed a prognostic signature and validated the efficacy in two independent cohorts. We also explored the differences of immune infiltration and tumor mutational burden (TMB) between the different risk groups.Results: A total of 6,175 cell-type-specific DEGs were obtained through the single-cell analysis between normal and tumor cells in breast cancer, of which 1,768 genes intersected with the bulk RNA-seq data. An 18-gene signature was constructed to assess the outcomes in breast cancer patients. The efficacy of the signature was notably prominent in two independent cohorts. The low-risk group showed higher immune infiltration and lower TMB. Among the 18 genes in the signature, 16 were also differentially expressed in the bulk RNA-seq dataset.Conclusion: Cell-type-specific DEGs between normal and tumor cells were identified through single-cell transcriptome data. The signature constructed with these DEGs could stratify patients efficiently. The signature was also closely correlated with immune infiltration and TMB. Nearly all the genes in the signature were also differentially expressed at the bulk RNA-seq level.
Role of 5-methylcytosine in determining the prognosis, tumor microenvironment, and applicability of precision medicine in patients with hepatocellular carcinoma
Authors: Luan Mingyuan , Zhao Min , Wang Haiying , Xu Rongjian , Cai Jinzhen 
Published: September 2022

Background: 5-methylcytosine has a profound impact on the development and progression of hepatocellular carcinoma. The aim of this study was to investigate the usefulness of 5-methylcytosine in determining the prognosis, tumor microenvironment, and applicability of precision medicine in hepatocellular carcinoma.Methods: We collected data of seven hepatocellular carcinoma cohorts (The Cancer Genome Atlas, International Cancer Genome Consortium, GSE14520, GSE6764, GSE9843, GSE63898, GSE76427). An unsupervised clustering method was used to identify novel subtypes of hepatocellular carcinoma based on the expression 5-methylcytosine gene signatures. The 5-methylcytosine score was determined using the least absolute shrinkage and selection operator method based on the differential expression of genes in the identified subtypes. Subsequently, we investigated the association between 5-methylcytosine-based clusters (according to the 5-methylcytosine score) and clinical outcomes, immunophenotypes, classical molecular subtypes, and therapeutic opportunities in hepatocellular carcinoma. Finally, we examined the sensitivity of patients with high 5-methylcytosine score to drugs.Results: We identified two hepatocellular carcinoma-specific, 5-methylcytosine-based subtypes (clusters 1 and 2). Cluster 1 exhibited significantly higher 5-methylcytosine scores versus cluster 2. The 5-methylcytosine-based subtypes accurately predicted classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities for patients with hepatocellular carcinoma. Cluster 1 (high 5-methylcytosine score) was characterized by lower anticancer immunity and worse prognosis versus cluster 2 (low 5-methylcytosine score). Moreover, cluster 1 (high 5-methylcytosine score) exhibited low sensitivity to cancer immunotherapy, but high sensitivity to radiotherapy and targeted therapy with lenvatinib.Conclusion: The novel 5-methylcytosine-based subtypes (according to the 5-methylcytosine score) may reflect the prognosis, tumor microenvironment, and applicability of precision medicine in patients with hepatocellular carcinoma.
Tuning Rex rules HTLV-1 pathogenesis
Authors: Nakano Kazumi , Watanabe Toshiki 
Published: September 2022

HTLV-1 is an oncovirus causing ATL and other inflammatory diseases such as HAM/TSP and HU in about 5% of infected individuals. It is also known that HTLV-1-infected cells maintain a disease-free, immortalized, latent state throughout the lifetimes of about 95% of infected individuals. We believe that the stable maintenance of disease-free infected cells in the carrier is an intrinsic characteristic of HTLV-1 that has been acquired during its evolution in the human life cycle. We speculate that the pathogenesis of the virus is ruled by the orchestrated functions of viral proteins. In particular, the regulation of Rex, the conductor of viral replication rate, is expected to be closely related to the viral program in the early active viral replication followed by the stable latency in HTLV-1 infected T cells. HTLV-1 and HIV-1 belong to the family Retroviridae and share the same tropism, e.g., human CD4+ T cells. These viruses show significant similarities in the viral genomic structure and the molecular mechanism of the replication cycle. However, HTLV-1 and HIV-1 infected T cells show different phenotypes, especially in the level of virion production. We speculate that how the activity of HTLV-1 Rex and its counterpart HIV-1 Rev are regulated may be closely related to the properties of respective infected T cells. In this review, we compare various pathological aspects of HTLV-1 and HIV-1. In particular, we investigated the presence or absence of a virally encoded “regulatory valve” for HTLV-1 Rex or HIV-1 Rev to explore its importance in the regulation of viral particle production in infected T cells. Finally, wereaffirm Rex as the key conductor for viral replication and viral pathogenesis based on our recent study on the novel functional aspects of Rex. Since the activity of Rex is closely related to the viral replication rate, we hypothesize that the “regulatory valve” on the Rex activity may have been selectively evolved to achieve the “scenario” with early viral particle production and the subsequent long, stable deep latency in HTLV-1 infected cells.
Effects of dietary pyrroloquinoline quinone on growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, Pelteobagrus fulvidraco
Authors: Shi Qingchao , Wen Zhengyong , Wang Jun , Hu Peng , Zou Yuanchao , Wang Shuqi , Qin Chuanjie 
Published: September 2022

This study aimed to evaluate the impacts of dietary pyrroloquinoline quinone (PQQ) supplement on growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, Pelteobagrus fulvidraco. Triplicate groups of fish (n = 40) with an average weight of 5 g were fed with five gradient levels PQQ-incorporated diets (0 (basal), 1.5 mg/kg; 3.0 mg/kg; 4.5 mg/kg, 6.0 mg/kg) for 56 days. Our findings revealed that fish fed with the diets containing PQQ at the level of 3.0-6.0 mg/kg showed significantly higher final body weight, weight gain rate, and specific growth rate than those of that in the control group (P &lt; 0.05). The activities of protease were observed significantly increased in fish fed with diets containing 4.5 mg/kg and 6 mg/kg PQQ (P &lt; 0.05). Meanwhile, fish in 4.5 mg/kg PQQ group showed significantly lower levels of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and significantly higher level of the high-density lipoprotein cholesterol (P &lt; 0.05). The antioxidant-related parameters of superoxide dismutase and total antioxidant capacity were markedly elevated (P &lt; 0.05), while malondialdehyde content was significantly reduced in 3.0-6.0 mg/kg PQQ group (P &lt; 0.05). Meanwhile, the mRNA expression levels of growth-related genes (growth hormone, insulin-like growth factor 1, and insulin-like growth factor 2) were dramatically up-regulated in the liver of fish fed with the diets containing 3-6 mg/kg PQQ in comparison with the control group (P &lt; 0.05). In conclusion, dietary PQQ could improve the growth performance, serum biochemical parameters, antioxidant status, and growth-related genes expressions in juvenile yellow catfish, and the optimal dietary PQQ level was evaluated to be 4.92 mg/kg of dry diet for juvenile yellow catfish.
Valproic-induced Fanconi syndrome: Clinical features, risk factors, diagnosis and management
Authors: Wang Chunjiang , Zhou Yulu , Song Liying , Deng Zhenzhen , Fang Weijin 
Published: September 2022

ObjectiveAlthough Fanconi syndrome (FS) induced by valproate (VPA) has occasionally been reported, the detailed clinical features of the disease remain unclear. The aim of this study was to elucidate the clinical features of patients with VPA-induced FS.MethodsWe searched Chinese and English databases for all original studies, clinical reports, and case reports on VPA-induced FS published before March 2022.ResultsA total of 29 articles including 54 patients (28 males and 24 females) were included. The patients had a median age of 7 years (range 2–34 years), had severely disabled (87.0%), tube feeding (64.8%), and received an average of 1.8 medications other than VPA. The median duration of VPA treatment was 4 years (range 0.7–15.5). Pathological fractures (25.9%), unexplained fever (11.1%), muscle weakness (9.3%), and edema (9.3%) were the most common symptoms, while 18 patients were diagnosed in incidental laboratory tests. Blood tests revealed hypokalemia (69.2%), hypophosphatemia (98.0%), and hypouricemia (93.3%). Urinalysis revealed glucosuria (96.1%), proteinuria (100.0%), generalized hyperaminoaciduria (100.0 %), β2 macroglobulin (100.0%). Decreased percent total reabsorption of phosphate (%TRP) found in 94.1% of patients, and increased fractional excretion of uric acid (FEUA) were found in 100% of patients. The median time to resolution of FS after discontinuation of drug therapy was 3 months (range 0.25–18).ConclusionsThe possibility of FS needs to be considered with long-term VPA administration, especially in young, tube-fed, severely disabled patients who are co-administered with anticonvulsants. Patients receiving VPA should have regular blood and urine tests. Abnormal laboratory values returned to normal levels after VPA discontinuation.
At the limits of digital education. The importance of practical education for clinical competencies learning in the field of emergency medicine: A controlled non-randomized interventional study
Authors: Vogt Lina , Schauwinhold Michael , Rossaint Rolf , Schenkat Henning , Klasen Martin , Sopka Saša 
Published: September 2022

IntroductionA high-quality education of future physicians is essential. Modern approaches interlock the acquisition of theoretical knowledge and practical skills in a spiral curriculum, leading to a mutual learning benefit for knowledge and application. This model was challenged by the elimination of hands-on trainings during the pandemic, which were often replaced by purely digital teaching models. Given the holistic nature of the spiral curriculum, we assumed that a purely digital model would have an impact on knowledge acquisition due to missing hands-on learning opportunities. The aim of the study was to investigate, using an emergency seminar as an example, whether purely digital training leads to a difference in theoretical knowledge compared to the traditional model.Materials and methodsStudy design: We used a two-groups design comparing a sample of medical students taught in 2020 with a purely digital teaching format (DF;n= 152) with a historical control group taught with a traditional format (TF;n= 1060). Subject of investigation was a seminar on emergency medicine, taking place in the 4th year. Outcome parameters: The primary outcome parameter was the students' acquired knowledge, measured by the score achieved in the final exams. Students' evaluation of the seminar was used as a secondary outcome parameter.ResultsStudents in the DF group scored significantly lower than students in the TF group in the final exams. Students in the DF group rated the course significantly worse than students in the TF group.DiscussionThe study results illustrate that purely digital education leads to inferior knowledge acquisition compared to the traditional spiral curriculum. A possible explanation may lie in a deeper processing of the information (e.g., understanding the information by experience and analysis) and accordingly a better memory recall. Moreover, the students' critical appraisal of the DF may have had an unfavorable effect on learning performance. Moderating factors may be lower learning motivation or the “zoom fatigue” effect.ConclusionThese study results clearly illustrate the importance of hands-on teaching for knowledge acquisition. The interlocking of theoretical knowledge and practical skills, as ensured by the spiral curriculum, is essential.
A circulating miR-19b-based model in diagnosis of human breast cancer
Authors: Zhao Qian , Shen Lei , Lü Jinhui , Xie Heying , Li Danni , Shang Yuanyuan , Huang Liqun , Meng Lingyu , An Xuefeng , Zhou Jieru , Han Jing , Yu Zuoren 
Published: September 2022

Abstract Objective: Breast cancer (BC) is becoming the leading cause of cancer-related death in women all over the word. Identification of diagnostic biomarkers for early detection of BC is one of the most effective ways to reduce the mortality.Methods: Plasma samples from BC patients (n = 120) and normal controls (n = 50) were collected to determine the differentially expressed circulating miRNAs in BC patients. Binary logistic regression was applied to develop miRNA diagnostic models. Receiver operating characteristic (ROC) curves were applied to calculate the area under the curve (AUC). MMTV-PYMT mammary tumor mice were used to validate the expression change of those circulating miRNAs. Plasma samples from patients with other tumor types were collected to determine the specificity of the model in diagnosis of BC.Results: In the screening phase, 5 circulating miRNAs (miR-16, miR-17, miR-19b, miR-27a, and miR-106a) were identified as the most significantly upregulated miRNAs in plasma of BC patients. In consistence, the 5 miRNAs showed upregulation in the circulation of additional 80 BC patients in a tumor stage-dependent manner. Application of a tumor-burden mice model further confirmed upregulation of the 5 miRNAs in circulation. Based on these data, five models with diagnostic potential of BC were developed. Among the 5 miRNAs, miR-19b ranked at the top position with the highest specificity and the biggest contribution. In combination with miR-16 and miR-106a, a miR-19b-based 3-circulating miRNA model was selected as the best for further validation. Taken the samples together, the model showed 92% of sensitivity and 90% of specificity in diagnosis of BC. In addition, three other tumor types including prostate cancer, thyroid cancer and colorectal cancer further verified the specificity of the BC diagnostic model. Conclusion: The current study developed a miR-19b-based 3-miRNA model holding potential for diagnosis of BC using blood samples.
Type 2 diabetes is associated with increased risk of dementia, but not mild cognitive impairment: a cross-sectional study among the elderly in Chinese communities
Authors: Liu Guojun , Li Yong , Xu Yuzhen , Li Wei 
Published: September 2022

Background: Previous studies have confirmed that diabetes is associated with cognitive impairment, but there is little data on this among older Chinese.Methods: This study included 192 dementia patients, 610 patients with mild cognitive impairment (MCI), and 2,218 normal controls. Their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension), and diabetes information (such as whether you have diabetes, course of the disease, etc) were collected by standardized questionnaires. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, Moreover, 84 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included the hippocampus, the third, fourth, and fifth ventricles.Results: The proportion of type 2 diabetes was significantly higher in the dementia group (25.5%) than that in the normal elderly group (15.6%) and the MCI group (17.7%). By using stepwise multiple logistics regression analysis, we found that type 2 diabetes was associated with dementia (p = 0.005*, OR = 1.805, 95%CI: 1.199–2.761), but not with MCI (p &gt; 0.05). The volume of the fourth ventricle of the healthy elderly with diabetes was significantly larger than that of the healthy elderly without diabetes (p &lt; 0.05), but there was no statistical difference (p &gt; 0.05) in the volume of the hippocampus, the third ventricle, and the fifth ventricle between the two groups. However, we did not find an association between the fourth ventricle and cognitive scores (MMSE and MoCA).Conclusions: In conclusion, type 2 diabetes in elderly Chinese people is associated with dementia, but not MCI. Type 2 diabetes may impair cognitive function by affecting the volume of the fourth ventricle. However, larger longitudinal follow-up studies are needed to confirm these conclusions.
Genetic and molecular features of seizure-freedom following surgical resections for focal epilepsy: A pilot study
Authors: Louis Shreya , Busch Robyn M. , Lal Dennis , Hockings Jennifer , Hogue Olivia , Morita-Sherman Marcia , Vegh Deborah , Najm Imad , Ghosh Chaitali , Bazeley Peter , Eng Charis , Jehi Lara , Rotroff Daniel M. 
Published: September 2022

ObjectiveSeizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, and electrophysiological variables. In this pilot study, we investigated whether genetic and molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response to surgery.MethodsPost-operative seizure-outcomes were collected at last follow-up (&gt;6 months) for 201 adult patients with DRE who underwent surgery between 2004 and 2020. Resected tissue was sent for miRNA sequencing (n = 132) and mRNA sequencing (n = 135). Following the selection of 10 genes (SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1), we investigated SNPs in those 10 genes from previously acquired exome sequencing data (n = 106). Logistic regression was performed to test for associations between individual features (mRNAs, miRNAs, and SNPs) and post-operative seizure-outcome with an exploratory FDR P &lt; 0.25 as the threshold for significance. Post-operative time-to-seizure analyses were performed for each SNP using a Cox proportional hazards model.ResultsThe majority of patients (83%) had temporal lobe epilepsy. Mean age at surgery was 38.3 years, and 56% were female. Three SNPs (rs10276036, rs11975994, rs1128503) in multi-drug resistance gene, ABCB1, were associated with post-operative seizure outcomes. Patients with alternate alleles in ABCB1 were more likely to be seizure-free at last follow-up (52–56% reduction in seizure recurrence; FDR P = 0.24). All three SNPs were in linkage disequilibrium and highly correlated with each other. Median post-operative time-to-seizure was 63 months for patients with 2 alternate alleles, 24–33 months with 1 alternate allele, and 10–11 months with 0 alternate alleles. These SNPs improved outcome prediction beyond MRI and sex alone. No independent miRNAs or mRNAs were significantly associated with seizure-outcome (P &gt; 0.05). However, pathway analysis identified “cancer drug resistance by drug efflux” (mir-154 and mir-379) as enriched (P = 0.02), supporting the role of drug response genes in post-operative seizure recurrence.SignificanceABCB1 may have a role in epileptogenesis and surgery outcomes independent of its drug efflux activity necessitating further investigation. SNPs in ABCB1 may serve as independent predictors of post-operative outcome.
Case report: Combined acute revascularization in early bilateral carotid stent occlusion
Authors: Černík David , Bartoš Robert , Neradová Jarmila , Frenštátská Nicol , Cihlář Filip , Brušáková Štěpánka , Sameš Martin 
Published: September 2022

IntroductionThe introduction of a carotid stent involves the use of effective antiplatelet therapy to maintain stent patency. We present a case report of combined acute revascularization in a patient with occlusion in recently introduced stents of both carotid arteries.MethodsThe patient (male, 73 years) was admitted for stroke recurrence upon discontinuation of antiplatelet therapy. According to the CTA, the closure of implanted stents of both carotid arteries was confirmed. Intravenous thrombolysis and mechanical thrombectomy were performed with complete recanalization of the left carotid stent. At 3 days apart, clinical deterioration was found with progressive stent restenosis. Percutaneous transluminal stent angioplasty, mechanical embolectomy and prolonged low-dose intravenous thrombolysis have been used repeatedly.ResultsWith the impossibility of maintaining the patency of carotid stents even on the maximum drug therapy and despite endovascular procedures, bilateral neurosurgical revascularization of the middle cerebral arteries using ECIC bypasses was successfully performed. Prolonged low-dose intravenous thrombolysis (20 mg recombinant plasminogen aktivator (rTPA)/10 h) has proven to be an acute bridging therapy until surgery.ConclusionEarly occlusion of the carotid stent is a significant complication of endovascular treatment of stenotic arteries. ECIC bypass revascularization of the middle cerebral artery can be a highly effective therapeutic procedure.