bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning and bioinformatics-based insights into the potential targets of saponins in Paris polyphylla smith against non-small cell lung cancer
Authors: Wang Yue , Huang Xulong , Xian Bin , Jiang Huajuan , Zhou Tao , Chen Siyu , Wen Feiyan , Pei Jin 
Published: October 2022

Background: Lung cancer has the highest mortality rate among cancers worldwide, and non-small cell lung cancer (NSCLC) is the major lethal factor. Saponins in Paris polyphylla smith exhibit antitumor activity against non-small cell lung cancer, but their targets are not fully understood.Methods: In this study, we used differential gene analysis, lasso regression analysis and support vector machine recursive feature elimination (SVM-RFE) to screen potential key genes for NSCLC by using relevant datasets from the GEO database. The accuracy of the signature genes was verified by using ROC curves and gene expression values. Screening of potential active ingredients for the treatment of NSCLC by molecular docking of the reported active ingredients of saponins in Paris polyphylla Smith with the screened signature genes. The activity of the screened components and their effects on key genes expression were further validated by CCK-8, flow cytometry (apoptosis and cycling) and qPCR.Results: 204 differential genes and two key genes (RHEBL1, RNPC3) stood out in the bioinformatics analysis. Overall survival (OS), First-progression survival (FP) and post-progression survival (PPS) analysis revealed that low expression of RHEBL1 and high expression of RNPC3 indicated good prognosis. In addition, Polyphyllin VI(PPVI) and Protodioscin (Prot) effectively inhibited the proliferation of non-small cell lung cancer cell line with IC50 of 4.46 μM ± 0.69 μM and 8.09 μM ± 0.67μM, respectively. The number of apoptotic cells increased significantly with increasing concentrations of PPVI and Prot. Prot induces G1/G0 phase cell cycle arrest and PPVI induces G2/M phase cell cycle arrest. After PPVI and Prot acted on this cell line for 48 h, the expression of RHEBL1 and RNPC3 was found to be consistent with the results of bioinformatics analysis.Conclusion: This study identified two potential key genes (RHEBL1 and RNPC3) in NSCLC. Additionally, PPVI and Prot may act on RHEBL1 and RNPC3 to affect NSCLC. Our findings provide a reference for clinical treatment of NSCLC.
Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer
Authors: Zhu Baoxi , Wang Songping , Wang Rui , Wang Xiaoliang 
Published: October 2022

Background: Breast cancer is the mostly diagnosed cancer worldwide, and triple negative breast cancer (TNBC) has the worst prognosis. Cuproptosis is a newly identified form of cell death, whose mechanism has not been fully explored in TNBC. This study thought to unveil the potential association between cuproptosis and TNBC.Materials and Methods: Gene expression files with clinical data of TNBC downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were included in this study. Consensus clustering was utilized to perform molecular subtyping based on cuproptosis-associated genes. Limma package was applied to distinguish differentially expressed genes. Univariate Cox regression was used to identify prognostic genes. Least absolute shrinkage and selection operator and stepwise Akaike information criterion optimized and established a risk model.Results: We constructed three molecular subtypes based on cuproptosis-associated genes, and the cuproptosis-based subtyping showed a robustness in different datasets. Clust2 showed the worst prognosis and immune-related pathways such as chemokine signaling pathway were significantly activated in clust2. Clust2 also exhibited a high possibility of immune escape to immune checkpoint blockade. In addition, a six-gene risk model was established manifesting a high AUC score over 0.85 in TCGA dataset. High- and low-risk groups had distinct prognosis and immune infiltration. Finally, a nomogram was constructed with strong performance in predicting TNBC prognosis than the staging system.Conclusion: The molecular subtyping system related to cuproptosis had a potential in guiding immunotherapy for TNBC patients. Importantly, the six-gene risk model was effective and reliable to predict TNBC prognosis.
Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19
Authors: Lapadula Giuseppe , Leone Roberto , Bernasconi Davide Paolo , Biondi Andrea , Rossi Emanuela , D’Angiò Mariella , Bottazzi Barbara , Bettini Laura Rachele , Beretta Ilaria , Garlanda Cecilia , Valsecchi Maria Grazia , Mantovani Alberto , Bonfanti Paolo 
Published: October 2022

BackgroundPTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19.MethodsLevels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method.ResultsUpon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P&lt;0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P&lt;0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049).ConclusionsHigh PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.
Development of a novel glycolysis-related genes signature for isocitrate dehydrogenase 1-associated glioblastoma multiforme
Authors: Cai Xiaomin , Chen Zheng , Huang Caiquan , Shen Jie , Zeng Wenxian , Feng Shuang , Liu Yu , Li Shiting , Chen Ming 
Published: October 2022

BackgroundThe significant difference in prognosis between IDH1 wild-type and IDH1 mutant glioblastoma multiforme (GBM) may be attributed to their metabolic discrepancies. Hence, we try to construct a prognostic signature based on glycolysis-related genes (GRGs) for IDH1-associated GBM and further investigate its relationships with immunity.MethodsDifferentially expressed GRGs between IDH1 wild-type and IDH1 mutant GBM were screened based on the TCGA database and the Molecular Signature Database (MSigDB). Consensus Cluster Plus analysis and KEGG pathway analyses were used to establish a new GRGs set. WGCNA, univariate Cox, and LASSO regression analyses were then performed to construct the prognostic signature. Then, we evaluated association of the prognostic signature with patients’ survival, clinical characteristics, tumor immunogenicity, immune infiltration, and validated one hub gene.Results956 differentially expressed genes (DEGs) between IDH1 wild-type and mutant GBM were screened out and six key prognostically related GRGs were rigorously selected to construct a prognostic signature. Further evaluation and validation showed that the signature independently predicted GBM patients’ prognosis with moderate accuracy. In addition, the prognostic signature was also significantly correlated with clinical traits (sex and MGMT promoter status), tumor immunogenicity (mRNAsi, EREG-mRNAsi and HRD-TAI), and immune infiltration (stemness index, immune cells infiltration, immune score, and gene mutation). Among six key prognostically related GRGs, CLEC5A was selected and validated to potentially play oncogenic roles in GBM.ConclusionConstruction of GRGs prognostic signature and identification of close correlation between the signature and immune landscape would suggest its potential applicability in immunotherapy of GBM in the future.
Vasculitis and familial Mediterranean fever: Description of 22 French adults from the juvenile inflammatory rheumatism cohort
Authors: Abbara Salam , Monfort Jean-Benoit , Savey Léa , Moguelet Philippe , Saadoun David , Bachmeyer Claude , Fain Olivier , Terrier Benjamin , Amoura Zahir , Mathian Alexis , Gilardin Laurent , Buob David , Job-Deslandre Chantal , Dufour Jean-François , Sberro-Soussan Rebecca , Grateau Gilles , Georgin-Lavialle Sophie 
Published: October 2022

ObjectiveThe frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases.MethodsPatients with vasculitis were selected from patients followed for FMF in the French JIR-cohort.ResultsTwenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications.ConclusionThis study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients.
Establishment and validation of the survival prediction risk model for appendiceal cancer
Authors: Liu Tao , Mi Junli , Wang Yafeng , Qiao Wenjie , Wang Chenxiang , Ma Zhijun , Wang Cheng 
Published: October 2022

ObjectiveEstablishing a risk model of the survival situation of appendix cancer for accurately identifying high-risk patients and developing individualized treatment plans.MethodsA total of 4,691 patients who were diagnosed with primary appendix cancer from 2010 to 2016 were extracted using Surveillance, Epidemiology, and End Results (SEER) * Stat software. The total sample size was divided into 3,283 cases in the modeling set and 1,408 cases in the validation set at a ratio of 7:3. A nomogram model based on independent risk factors that affect the prognosis of appendix cancer was established. Single-factor Cox risk regression, Lasso regression, and multifactor Cox risk regression were used for analyzing the risk factors that affect overall survival (OS) in appendectomy patients. A nomogram model was established based on the independent risk factors that affect appendix cancer prognosis, and the receiver operating characteristic curve (ROC) curve and calibration curve were used for evaluating the model. Survival differences between the high- and low-risk groups were analyzed through Kaplan–Meier survival analysis and the log-rank test. Single-factor Cox risk regression analysis found age, ethnicity, pathological type, pathological stage, surgery, radiotherapy, chemotherapy, number of lymph nodes removed, T stage, N stage, M stage, tumor size, and CEA all to be risk factors for appendiceal OS. At the same time, multifactor Cox risk regression analysis found age, tumor stage, surgery, lymph node removal, T stage, N stage, M stage, and CEA to be independent risk factors for appendiceal OS. A nomogram model was established for the multifactor statistically significant indicators. Further stratified with corresponding probability values based on multifactorial Cox risk regression, Kaplan–Meier survival analysis found the low-risk group of the modeling and validation sets to have a significantly better prognosis than the high-risk group (p &lt; 0.001).ConclusionThe established appendix cancer survival model can be used for the prediction of 1-, 3-, and 5-year OS and for the development of personalized treatment options through the identification of high-risk patients.
Genomic diversity of resistant and virulent factors of Burkholderia pseudomallei clinical strains recovered from Guangdong using whole genome sequencing
Authors: Shafiq Muhammad , Ke Bixia , Li Xin , Zeng Mi , Yuan Yumeng , He Dongmei , Deng Xiaoling , Jiao Xiaoyang 
Published: October 2022

BackgroundBurkholderia pseudomallei (B. pseudomallei) is a highly infectious agent and causes melioidosis, in both humans and animals, which is endemic in Southeast Asia and Northern Australia.ObjectivesThis study aims to determine the molecular epidemiology, resistant determinants, and genomic diversity of the clinical isolates of B. pseudomallei to further elucidate the phylogenetic and evolutionary relationship of the strains with those in other endemic regions.MethodsIn this study, we obtained eight clinical B. pseudomallei isolates from Guangdong province from 2018 to 2019. All the isolates were sequenced using the Illumina NovaSeq platform. The draft genomes of B. pseudomallei were further used to find antibiotic-resistant genes (ARGs), virulence factors, and gene mutations. Multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis were performed to characterize the diversity and epidemiology of the strains.ResultsAll isolates were susceptible to antibiotics commonly used for melioidosis treatment. Class D beta-lactamases genes OXA-57 and OXA-59, as well as various mutation factors such as amrA, amrB, omp38, gyrA, and ceoB were identified. MLST analysis of the B. pseudomallei strains identified eight different sequence types (STs): ST1774, ST1775, ST271, ST562, ST46, ST830, ST1325, and ST10. Phylogenetic analysis found that the strains used in this study showed high genetic diversity. We also report 165 virulence factors among B. pseudomallei strains responsible for different neurological disorders, pneumonia, skin lesions, and abscesses. All strains recovered in this study were susceptible to commonly used antibiotics. However, high genetic diversity exists among the isolates. The surveillance, diagnosis, and clinical features of melioidosis varied in different geographical locations. These regional differences in the clinical manifestations have implications for the practical management of the disease.ConclusionThe present study reports the identification of different mutation and virulence factors among B. pseudomallei strains responsible for different neurological disorders, pneumonia, skin lesions, and abscesses.
MetaGT: A pipeline for de novo assembly of metatranscriptomes with the aid of metagenomic data
Authors: Shafranskaya Daria , Kale Varsha , Finn Rob , Lapidus Alla L. , Korobeynikov Anton , Prjibelski Andrey D. 
Published: October 2022

While metagenome sequencing may provide insights on the genome sequences and composition of microbial communities, metatranscriptome analysis can be useful for studying the functional activity of a microbiome. RNA-Seq data provides the possibility to determine active genes in the community and how their expression levels depend on external conditions. Although the field of metatranscriptomics is relatively young, the number of projects related to metatranscriptome analysis increases every year and the scope of its applications expands. However, there are several problems that complicate metatranscriptome analysis: complexity of microbial communities, wide dynamic range of transcriptome expression and importantly, the lack of high-quality computational methods for assembling meta-RNA sequencing data. These factors deteriorate the contiguity and completeness of metatranscriptome assemblies, therefore affecting further downstream analysis.Here we present MetaGT, a pipeline for de novo assembly of metatranscriptomes, which is based on the idea of combining both metatranscriptomic and metagenomic data sequenced from the same sample. MetaGT assembles metatranscriptomic contigs and fills in missing regions based on their alignments to metagenome assembly. This approach allows to overcome described complexities and obtain complete RNA sequences, and additionally estimate their abundances. Using various publicly available real and simulated datasets, we demonstrate that MetaGT yields significant improvement in coverage and completeness of metatranscriptome assemblies compared to existing methods that do not exploit metagenomic data. The pipeline is implemented in NextFlow and is freely available from https://github.com/ablab/metaGT.
Case report: Long-term follow-up of two patients with LHON caused by DNAJC30:c.152G>A pathogenic variant-case series
Authors: Petrovic Pajic Sanja , Jarc-Vidmar Martina , Fakin Ana , Sustar Habjan Maja , Brecelj Jelka , Volk Marija , Maver Ales , Peterlin Borut , Hawlina Marko 
Published: October 2022

BackgroundWe present the disease course and long-term follow-up of two patients who were phenotypically diagnosed with atypical Leber Hereditary Optic Neuropathy (LHON) 14 and 12 years ago, respectively, whereby whole exome sequencing revealed recently described recessive DNAJC30:c.152G&gt;A 152 A&gt;G (p.Tyr51Cys) homozygous pathogenic variant with significant spontaneous visual acuity recovery in one.Case presentationTwo presented unrelated males with atypical LHON with sequential visual acuity (VA) loss were followed for many years. Both patients had negative family history. At the presentation at ages 17 (Case 1) and 18 years (Case 2), both had reduced visual acuity (Snellen): (Case 1) right eye (RE):CF 3m, left eye (LE):0.6, (Case 2) RE:0.2, LE:0.15; and color vision (Ishihara): (Case 1) 1/15 and 13/15; (Case 2) 2/15 and 3/15. Both had hyperemic optic disks (PNO) and central scotoma in their visual fields. Electrophysiology in the acute phase showed reduced and delayed visually evoked potentials (VEP) P100 in both patients, with reduced N95 amplitude in Case 2, and initially normal N95 amplitude in Case 1. Fluorescein angiography showed no early leakage with some late pooling at optic disks. Extensive clinical workout, including brain magnetic resonance imaging (MRI), aquaporin 4 (Aq4), and anti-myelin oligodendrocyte protein (anti-MOG) antibodies, was negative. Intravenous corticosteroids did not improve vision. Both experienced further deterioration several months after the onset accompanied by thinning of the peripapillary retinal nerve fiber layer (RNFL). Genetic testing for typical LHON pathogenic variants and whole mitochondrial DNA (mtDNA) sequencing was negative. 1 year after the onset, modest VA improvement began in Case 2 and continued over the next 3 years. VA improved bilaterally to 0.7, color vision 15/15, and islands of vision appeared within the visual field scotoma. VEP P100 peak time shortened, and amplitude increased, despite further RNFL thinning on optical coherent tomography (OCT). The patient's visual function remained stable during the entire 12-year follow-up period. Case 1 experienced modest VA improvement to 0.1 with some improvement in the visual field seven years after the disease onset, remaining stable during the entire 14-year follow-up period. VEP P100 wave remained undetectable.ConclusionsPresented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G&gt;A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.
Effect of transcutaneous posterior tibial nerve stimulation and repetitive transcranial magnetic stimulation on neurogenic overactive bladder symptoms in female patients with multiple sclerosis: The study protocol of a randomized controlled study
Authors: Atak Çakir Pinar , Mutluay Fatma , Hanoğlu Lütfü , Güzelburç Vahit 
Published: October 2022

IntroductionNeurogenic bladder is frequently seen in patients with multiple sclerosis (MS). Electrical stimulation methods (neuromodulation) can be used for patients that have persistent symptoms despite pharmacological treatment. This study aims to compare the effects of two different neuromodulation techniques used in the treatment of neurogenic bladder.Methods and analysisThis is a single-center randomized controlled trial for MS patients with neurogenic bladder. Patients determined to be eligible according to the study criteria will be randomized into two treatment groups: the transcutaneous posterior tibial nerve stimulation (PTNS) and repetitive transcranial magnetic stimulation (rTMS) groups. Each group will include eight patients. The patients will be treated for a total of 10 sessions for two consecutive weeks. The pressure-flow study will be used to compare the initial and final urodynamic results as the primary outcome. All the participants will fill in a 3-day bladder diary before and after the treatments in each group. Patients will also be asked to complete specific questionnaires for incontinence and quality of life (QOL): Overactive Bladder Questionnaire-V8 score (OAB-V8), Incontinence Severity Index (ISI), Incontinence Quality of Life Scale score (I-QOL), International Incontinence Questionnaire (ICIQ-SF) score, and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) score) as the secondary outcomes.Ethics and disseminationAn ethical approval number was obtained from the Non-Invasive Clinical Research Ethics Committee of Istanbul Medipol University (ethical approval number: 768). Support was received within the scope of the Istanbul Medipol University Scientific Research Project with project number 2020—2017. The result of this study will be published in a peer-reviewed journal.Trial registrationNCT05312138.