bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
Authors: Zhao Songyun , Zhang Li , Ji Wei , Shi Yachen , Lai Guichuan , Chi Hao , Huang Weiyi , Cheng Chao 
Published: October 2022

Background: Parkinson’s disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases.Methods: This study aimed to identify potential novel biomarkers of Parkinson’s disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson’s specimens using consensus clustering methods.Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson’s disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function.Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson’s disease through immune cell infiltration.
Exploration the global single-cell ecological landscape of adenomyosis-related cell clusters by single-cell RNA sequencing
Authors: Lin Jiajing , Liu Li , Zheng Fengque , Chen Saiqiong , Yang Weiwei , Li Jingjing , Mo Steven , Zeng Ding-Yuan 
Published: October 2022

Background: Adenomyosis (AM) is a common benign uterine disease that threatens the normal life of patients. Cells associated with microenvironmental immune ecology are crucial in AM, although they are not as well understood at the cellular level.Methods: Single-cell sequencing (scRNA-seq) data were used to construct an AM global single-cell map, to further identify relevant cell clusters and infer chromosomal copy number variation (CNV) in AM samples. The biological functions of cell clusters were explored and cellular evolutionary processes were inferred by enrichment analysis and pseudotime analysis. In addition, a gene regulatory network (GRN) analysis was constructed to explore the regulatory role of transcription factors in AM progression.Results: We obtained the expression profiles of 42260 cells and identified 10 cell clusters. By comparing the differences in cell components between AM patients and controls, we found that significant abundance of endometrial cells (EC), epithelial cells (Ep), endothelial cells (En), and smooth muscle cells (SMC) in AM patients. Cell clusters with high CNV levels possessing tumour-like features existed in the ectopic endometrium samples. Moreover, the Ep clusters were significantly involved in leukocyte transendothelial cell migration and apoptosis, suggesting an association with cell apoptosis and migration. En clusters were mainly involved in pathways in cancer and apoptosis, indicating that En has certain malignant features.Conclusion: This study identified cell clusters with immune-related features, investigated the changes in the immune ecology of the microenvironment of these cells during AM, and provided a new strategy for the treatment of AM.
Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial
Authors: Lorentzen Cathrine Lund , Martinenaite Evelina , Kjeldsen Julie Westerlin , Holmstroem Rikke Boedker , Mørk Sofie Kirial , Pedersen Ayako Wakatsuki , Ehrnrooth Eva , Andersen Mads Hald , Svane Inge Marie 
Published: October 2022

BackgroundArginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of arginase-1-specific T cells may convert the immunosuppressive tumor microenvironment and induce or strengthen local Th1 inflammation. In the current clinical study, we examined the safety and immunogenicity of arginase-1-based peptide vaccination.MethodsIn this clinical phase I trial, ten patients with treatment-refractory progressive solid tumors were treated. The patients received an arginase-1 peptide vaccine comprising three 20-mer peptides from the ARG1 immunological “hot spot” region in combination with the adjuvant Montanide ISA-51. The vaccines were administered subcutaneously every third week (maximum 16 vaccines). The primary endpoint was to evaluate safety assessed by Common Terminology Criteria for Adverse Events 4.0 and laboratory monitoring. Vaccine-specific immune responses were evaluated using enzyme-linked immune absorbent spot assays and intracellular cytokine staining on peripheral blood mononuclear cells. Clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors 1.1.ResultsThe vaccination was feasible, and no vaccine-related grade 3–4 adverse events were registered. Nine (90%) of ten patients exhibited peptide-specific immune responses in peripheral blood mononuclear cells. Six (86%) of the seven evaluable patients developed a reactive T cell response against at least one of the ARG1 peptides during treatment. A phenotypic classification revealed that arginase-1 vaccine-specific T cells were both CD4+ T cells and CD8+ T cells. Two (20%) of ten patients obtained stable disease for respectively four- and seven months on vaccination treatment.ConclusionThe peptide vaccine against arginase-1 was safe. Nine (90%) of ten patients had measurable peptide-specific responses in the periphery blood, and two (20%) of ten patients attained stable disease on protocol treatment.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03689192, identifier NCT03689192.
A prognostic signature consisting of metabolism-related genes and SLC17A4 serves as a potential biomarker of immunotherapeutic prediction in prostate cancer
Authors: Li He , Gu Jie , Tian Yuqiu , Li Shuyu , Zhang Hao , Dai Ziyu , Wang Zeyu , Zhang Nan , Peng Renjun 
Published: October 2022

BackgroundProstate cancer (PCa), a prevalent malignant cancer in males worldwide, screening for patients might benefit more from immuno-/chemo-therapy remained inadequate and challenging due to the heterogeneity of PCa patients. Thus, the study aimed to explore the metabolic (Meta) characteristics and develop a metabolism-based signature to predict the prognosis and immuno-/chemo-therapy response for PCa patients.MethodsDifferentially expressed genes were screened among 2577 metabolism-associated genes. Univariate Cox analysis and random forest algorithms was used for features screening. Multivariate Cox regression analysis was conducted to construct a prognostic Meta-model based on all combinations of metabolism-related features. Then the correlation between MetaScore and tumor was deeply explored from prognostic, genomic variant, functional and immunological perspectives, and chemo-/immuno-therapy response. Multiple algorithms were applied to estimate the immunotherapeutic responses of two MeteScore groups. Further in vitro functional experiments were performed using PCa cells to validate the association between the expression of hub gene SLC17A4 which is one of the model component genes and tumor progression. GDSC database was employed to determine the sensitivity of chemotherapy drugs.ResultsTwo metabolism-related clusters presented different features in overall survival (OS). A metabolic model was developed weighted by the estimated regression coefficients in the multivariate Cox regression analysis (0.5154*GAS2 + 0.395*SLC17A4 - 0.1211*NTM + 0.2939*GC). This Meta-scoring system highlights the relationship between the metabolic profiles and genomic alterations, gene pathways, functional annotation, and tumor microenvironment including stromal, immune cells, and immune checkpoint in PCa. Low MetaScore is correlated with increased mutation burden and microsatellite instability, indicating a superior response to immunotherapy. Several medications that might improve patients` prognosis in the MetaScore group were identified. Additionally, our cellular experiments suggested knock-down of SLC17A4 contributes to inhibiting invasion, colony formation, and proliferation in PCa cells in vitro.ConclusionsOur study supports the metabolism-based four-gene signature as a novel and robust model for predicting prognosis, and chemo-/immuno-therapy response in PCa patients. The potential mechanisms for metabolism-associated genes in PCa oncogenesis and progression were further determined.
Meeting future NOX emission regulations by adding an electrically heated mixer
Authors: Meruva P. , Matheaus A. , Sharp C. A. , McCarthy J. E. , Masoudi M. , Poliakov N. , Noorfeshan S. 
Published: October 2022

New regulations by the California Air Resources Board (CARB) demand a stringent 0.02 g/hp-hr tailpipe NOx limit by the year 2027, requiring Selective Catalytic Reduction (SCR) catalysts to provide high NOx conversions even at low (below 200°C) exhaust temperatures. This work describes utilizing an Electrically Heated Mixer System (EHM system) upstream of a Light-Off Selective Catalytic Reduction (LO-SCR) catalyst followed by a conventional aftertreatment (AT) system containing DOC, DPF, and SCR, enabling high NOx conversions meeting CARB’s NOx emission target. The AT catalysts were hydrothermally aged to Full Useful Life. Conventional unheated Diesel Exhaust Fluid (DEF) was injected upstream of both the LO-SCR and primary downstream SCR. The EHM system allowed for DEF to be injected as low as 130°C upstream of the LO-SCR, whereas, in previous studies, unheated DEF was injected at 180°C or dosed at 130°C with heated DEF. The combination of unheated DEF, EHM system, LO-SCR, and downstream SCR enabled the needed increase in NOx efficiency in low exhaust temperatures, which was observed in drive cycles such as in cold-FTP, LLC, and World Harmonized Transient Cycle (WHTC). There were several-fold reductions in tailpipe NOx using this configuration compared to its baseline: 3.3-fold reduction in FTP, 22-fold in Low Load Cycle (LLC), 38-fold in Beverage Cycle, 8-fold in “Stay Hot” Cycle, and 10-fold in WHTC. Finally, it is shown that the EHM system can heat the exhaust gas, such as during a cold start, without needing additional heating hardware integrated into the system. These results were observed without performing changes in the engine base calibration.
A new small molecule DHODH-inhibitor [KIO-100 (PP-001)] targeting activated T cells for intraocular treatment of uveitis — A phase I clinical trial
Authors: Thurau Stephan , Deuter Christoph M. E. , Heiligenhaus Arnd , Pleyer Uwe , Van Calster Joachim , Barisani-Asenbauer Talin , Obermayr Franz , Sperl Stefan , Seda-Zehetner Romana , Wildner Gerhild 
Published: October 2022

Uveitis is a T cell-mediated, intraocular inflammatory disease and one of the main causes of blindness in industrialized countries. There is a high unmet need for new immunomodulatory, steroid-sparing therapies, since only ciclosporin A and a single TNF-α-blocker are approved for non-infectious uveitis. A new small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), an enzyme pivotal forde novosynthesis of pyrimidines, has a high potency for suppressing T and B cells and has already proven highly effective for treating uveitis in experimental rat models. Systemic and intraocular application of KIO-100 (PP-001) (previously called PP-001, now KIO-100) could efficiently suppress rat uveitis in a preventive as well as therapeutic mode. Here we describe the outcome of the first clinical phase 1 trial comparing three different doses of a single intraocular injection of KIO-100 (PP-001) in patients with non-infectious posterior segment uveitis. No toxic side effects on intraocular tissues or other adverse events were observed, while intraocular inflammation decreased, and visual acuity significantly improved. Macular edema, a sight-threatening complication in uveitis, showed regression 2 weeks after intraocular KIO-100 (PP-001) injection in some patients, indicating that this novel small molecule has a high potential as a new intraocular therapy for uveitis.Clinical trial registration[https://www.clinicaltrials.gov/ct2/show/NCT03634475], identifier [NCT03634475].
Case report: Visual acuity loss as a warning sign of ocular syphilis: A retrospective analysis of 17 cases
Authors: Xu Yating , Li Jingjing , Xu Yuxuan , Xia Wei , Mo Xingfan , Feng Mingzhi , He Fanghua , Li Shanshan , Du Fangzhi , Wang Qianqiu , Wu Minzhi 
Published: October 2022

ObjectivesTo define the clinical features of ocular syphilis and analyze the cerebrospinal fluid (CSF) of ocular syphilis patients to determine the co-occurrence of neurosyphilis.MethodsThis was a retrospective study of 17 patients (23 eyes) with ocular syphilis admitted to the Fifth People's Hospital, Suzhou, China from September 2017 to December 2021. Clinical manifestations, laboratory tests, treatment, and clinical outcomes were analyzed, and a review was conducted.ResultsEight males (12 eyes) and nine females (11 eyes) were enrolled. Mean patient age was 49.06 ± 3.47 years. The total manifestation time for ocular symptoms ranged from 10 days to 6 years. The cohort was comprised of three cases of early syphilis, four cases of late syphilis, and ten cases of unknown stage. The primary complaints were decreased visual acuity in 15 cases (21 eyes), ptosis in 1 case (1 eye), and loss of light perception in 1 case (1 eye). Cases were diagnosed as chorioretinitis in 7 cases (8 eyes), optic nerve retinitis in 4 cases (6 eyes), optic neuritis in 4 cases (7 eyes), and oculomotor nerve palsy in 1 case (1 eye), syphilitic stromal keratitis in 1 case (1 eye). Serum HIV antibody was positive in one case(Nos.2). All patients had reactive serum Treponema Pallidum Particle Agglutination (TPPA) and Toluidine Red Unheated Serum Test (TRUST). All patients underwent CSF examination. CSF white blood cell count was ≥5 × 106/L in 13 cases, CSF protein was &gt;500 mg/L in 6 cases, TPPA was reactive in 15 cases, and TRUST was reactive in 5 cases. Eleven cases were also diagnosed with neurosyphilis. Patients were treated with either penicillin G sodium or ceftriaxone sodium. At time of discharge, 12 patients reported improved visual acuity. Abnormal serum or CSF examination improved in ten patients during the 6–12 month follow-up.ConclusionVisual acuity loss is a warning indicator of ocular syphilis. Ocular syphilis primarily manifests as posterior uveitis, involving the choroid, retina, and optic nerve, and often co-occurs with neurosyphilis. Effective treatment should be administered immediately to avoid irreversible visual impairment and other serious adverse outcomes.
Analysis of influencing factors of early neurological improvement after intravenous rt-PA thrombolysis in acute anterior circulation ischemic stroke
Authors: Xiufu Zhang , Ruipeng Liang , Jun Zhou , Yonglong Li , Yulin Wang , Jian Zeng , Xianglin Chen , Lan Shen , Zuowen Zhang 
Published: October 2022

Background and objectiveIt has been widely reported that Early neurological improvement (ENI) after rt-PA intravenous thrombolysis contributes to a good long-term prognosis in patients experiencing acute ischemic stroke (AIS). However, which clinical factors influence after intravenous administration of recombinant tissue-type plasminogen activator (IV-rt PA) in AIS patients ENI is still unclear. This study aimed to evaluate the impact of influencing factors on the benefit of ENI after intravenous thrombolysis neurological improvement after IV-rt PA.MethodsThe data of 73 patients with acute anterior circulation ischemic stroke who received intravenous thrombolysis with rt-PA in Chongqing University Jiangjin Hospital from January 2021 to July 2022 were retrospectively studied. According to the change rate of 24 h NISHH score, the research subjects were divided into the recovery group, the significant curative effect group, the curative effect group and the no curative effect group, the ENI after intravenous thrombolysis with rt-PA was defined as the improvement rate of National Institutes of Health Stroke Scale (NIHSS)score &gt;46% at 24 h after IV-rt PA, and univariate factor analysis was used Clinical factors associated with ENI after intravenous thrombolysis.ResultsAccording to the 24-h NIHSS improvement rate of rt-PA intravenous thrombolysis in patients with acute anterior circulation ischemic stroke, 35 cases (47.95%) of the study population had ENI. There was no statistical difference between the improvement and non-improvement group in general demographic data, stroke TOAST classification, stroke risk factors (history of stroke, heart disease, hyperlipidemia, hypertension), and laboratory test data. There was a statistically significant difference in the random blood glucose levels between the two groups (p &lt; 0.001, t = 3.511).ConclusionThe effect of rt-PA intravenous thrombolysis within the time window of patients with acute anterior circulation ischemic stroke is significant, but the ENI after thrombolysis is easily affected by the level of blood glucose; diabetes is the most important factor affecting the acute anterior circulation ischemic stroke patients Clinical factors of ENI after intravenous thrombolysis with rt-PA.
A prognostic signature of cuproptosis and TCA-related genes for hepatocellular carcinoma
Authors: Zhang Qi , Ma Longping , Zhou Hongyuan , Zhou Yanzhao , Liu Shuaijing , Li Qiang 
Published: October 2022

BackgroundHepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Cuproptosis is a newly defined form of cell death. Copper ion induces cell death by binding to the tricarboxylic acid cycle (TCA). The effect of cuproptosis-related and TCA-related genes on the clinical prognosis of HCC is still unclear. In this study, we explores the genetic changes of cuproptosis-related genes that affect the TCA process and their potential therapeutic value in HCC patients.MethodsThe cuproptosis and TCA-related genes were obtained from cuproptosis-related articles and the molecular signatures database. The prognosis signatures of eight related genes were constructed using the last absolute shrinkage and selection operator (LASSO), and Receiver Operating Characteristic (ROC) curves were used to evaluate the signature. In addition, we analyzed downstream functional enrichment and immune infiltration to explore cuproptosis-inducing drugs and immunotherapeutic responses. All these analyses were validated using multiple datasets of the International Cancer Genome Consortium (ICGC).ResultsTCA and copper malnutrition-related genes (CDKN2A, IDH1, OGDHL, IDH3G, IDH3B, GLS, DLAT, LIPT1) were finally included. According to the risk score, they were divided into high-risk and low-risk groups. Survival analysis showed that the overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. We established a risk prognostic feature to predict the OS of patients with HCC. Based on this feature and the clinical stage, we constructed a nomogram. Functional enrichment analysis revealed pathways related to organelle division and the cell cycle. Different risk scores had different immune abundances in immune cells (including macrophages and regulatory T-cells) and immune pathways (including antigen-presenting cells co-stimulation). Moreover, the drug sensitivity of eleschomol and PD-L1 in the high-risk group was better than that in the low-risk group. The status of TP53 somatic mutation was also closely related to the risk score.ConclusionIn this study, we established a new prediction signature of eight genes related to cuproptosis and the TCA process, which can effectively predict the prognosis of HCC patients.
Specific imaging features indicate the clinical features of patients with hepatic perivascular epithelioid cell tumor by comparative analysis of CT and ultrasound imaging
Authors: Gao Xudong , Tang Hewen , Wang Jianying , Yao Qian , Wang Hong , Wang Yan , Ma Mingming , Yang Wei , Yan Kun , Wu Wei 
Published: October 2022

ObjectiveThe objective of the study was to explore the CT and ultrasound features and clinical significance of perivascular epithelioid cell tumor (PEComa) of the liver.MethodsEleven hepatic PEComa patients treated in our hospital were retrospectively analyzed based on the characteristics of the imaging results of the patients, including conventional ultrasound, CDFI, contrast-enhanced ultrasound (CEUS), and contrast-enhanced CT (CECT).ResultsCT scans showed that all lesions were hypodense. Ultrasonography showed that lesions were either hyperechoic (4/11, 36.36%), hypoechoic (4/11, 36.36%), isoechoic (1/11, 9.09%), or heterogeneously echoic (2/11, 18.18%). CDFI showed that most of the lesions had an abundant blood supply (9/11, 81.82%). Whether on CT scan or ultrasonography, the margins of the lesions were dominated by clear margins. Ultrasonography revealed more features: hyperechoic patterns around lesions (3/11, 27.27%) and lateral shadow (5/11, 45.45%). The CDFI showed that large blood vessels were observed around the lesions (9/11, 81.82%). CECT shows two enhancement patterns: “fast in and fast out (FIFO)” (8/11, 72.72%) and “fast in and slow out (FISO)” (3/11, 27.27%). CEUS shows that all lesions had the enhancement pattern of “FISO,” which was different from CECT. All lesions displayed rapid enhancement during HAP in CEUS during 7–20 s. Four patients (36.36%) washed out at 60–180 s, another four (36.36%) washed out at 180–300 s, and the remaining three patients (27.27%) showed no signs of washout even at 360 s.ConclusionSome imaging features, such as clear margins, peripheral hyperechoic around the lesion, lateral shadow, the large blood vessels around lesions, and the “FISO” enhancement pattern, may indicate expansive growth of the tumor and be helpful in the diagnosis of PEComa. Ultrasound images may provide more details for clinical reference.