bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-Cancer Analysis of the Solute Carrier Family 39 Genes in Relation to Oncogenic, Immune Infiltrating, and Therapeutic Targets
Authors: Qu Yi-Yuan , Guo Rong-Yan , Luo Meng-Ling , Zhou Quan 
Published: December 2021

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.
PseUdeep: RNA Pseudouridine Site Identification with Deep Learning Algorithm
Authors: Zhuang Jujuan , Liu Danyang , Lin Meng , Qiu Wenjing , Liu Jinyang , Chen Size 
Published: December 2021

Background: Pseudouridine (Ψ) is a common ribonucleotide modification that plays a significant role in many biological processes. The identification of Ψ modification sites is of great significance for disease mechanism and biological processes research in which machine learning algorithms are desirable as the lab exploratory techniques are expensive and time-consuming.Results: In this work, we propose a deep learning framework, called PseUdeep, to identify Ψ sites of three species: H. sapiens, S. cerevisiae, and M. musculus. In this method, three encoding methods are used to extract the features of RNA sequences, that is, one-hot encoding, K-tuple nucleotide frequency pattern, and position-specific nucleotide composition. The three feature matrices are convoluted twice and fed into the capsule neural network and bidirectional gated recurrent unit network with a self-attention mechanism for classification.Conclusion: Compared with other state-of-the-art methods, our model gets the highest accuracy of the prediction on the independent testing data set S-200; the accuracy improves 12.38%, and on the independent testing data set H-200, the accuracy improves 0.68%. Moreover, the dimensions of the features we derive from the RNA sequences are only 109,109, and 119 in H. sapiens, M. musculus, and S. cerevisiae, which is much smaller than those used in the traditional algorithms. On evaluation via tenfold cross-validation and two independent testing data sets, PseUdeep outperforms the best traditional machine learning model available. PseUdeep source code and data sets are available at https://github.com/dan111262/PseUdeep.
Antibody Response and Safety After mRNA-1273 SARS-CoV-2 Vaccination in Peritoneal Dialysis Patients – the Vienna Cohort
Authors: Beilhack Georg , Monteforte Rossella , Frommlet Florian , Gaggl Martina , Strassl Robert , Vychytil Andreas 
Published: December 2021

BackgroundDialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare.MethodsIn this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients.ResultsFour weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05).ConclusionsPeritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.
An Immunocompetent Microphysiological System to Simultaneously Investigate Effects of Anti-Tumor Natural Killer Cells on Tumor and Cardiac Microtissues
Authors: Nguyen Oanh T. P. , Misun Patrick M. , Lohasz Christian , Lee Jihyun , Wang Weijia , Schroeder Timm , Hierlemann Andreas 
Published: December 2021

Existing first-line cancer therapies often fail to cope with the heterogeneity and complexity of cancers, so that new therapeutic approaches are urgently needed. Among novel alternative therapies, adoptive cell therapy (ACT) has emerged as a promising cancer treatment in recent years. The limited clinical applications of ACT, despite its advantages over standard-of-care therapies, can be attributed to (i) time-consuming and cost-intensive procedures to screen for potent anti-tumor immune cells and the corresponding targets, (ii) difficulties to translate in-vitro and animal-derived in-vivo efficacies to clinical efficacy in humans, and (iii) the lack of systemic methods for the safety assessment of ACT. Suitable experimental models and testing platforms have the potential to accelerate the development of ACT. Immunocompetent microphysiological systems (iMPS) are microfluidic platforms that enable complex interactions of advanced tissue models with different immune cell types, bridging the gap between in-vitro and in-vivo studies. Here, we present a proof-of-concept iMPS that supports a triple culture of three-dimensional (3D) colorectal tumor microtissues, 3D cardiac microtissues, and human-derived natural killer (NK) cells in the same microfluidic network. Different aspects of tumor-NK cell interactions were characterized using this iMPS including: (i) direct interaction and NK cell-mediated tumor killing, (ii) the development of an inflammatory milieu through enrichment of soluble pro-inflammatory chemokines and cytokines, and (iii) secondary effects on healthy cardiac microtissues. We found a specific NK cell-mediated tumor-killing activity and elevated levels of tumor- and NK cell-derived chemokines and cytokines, indicating crosstalk and development of an inflammatory milieu. While viability and morphological integrity of cardiac microtissues remained mostly unaffected, we were able to detect alterations in their beating behavior, which shows the potential of iMPS for both, efficacy and early safety testing of new candidate ACTs.
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients
Authors: Caldrer Sara , Mazzi Cristina , Bernardi Milena , Prato Marco , Ronzoni Niccolò , Rodari Paola , Angheben Andrea , Piubelli Chiara , Tiberti Natalia 
Published: December 2021

BackgroundThe host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify.MethodsWe performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses.ResultsThe immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%.ConclusionsThe present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.
In vivo Imaging of Retina and Choroid in Guinea Pigs
Authors: Dong Li , Li Yi Fan , Jiang Xue , Lan Yin Jun , Shao Lei , Jonas Jost B. , Wei Wen Bin 
Published: December 2021

Purpose: To evaluate the feasibility of in-vivo imaging of the retina and choroid using spectral domain optical coherence tomography (OCT) in guinea pigs.Methods: The study included 19 pigmented guinea pigs (age: 3–4 weeks) which underwent sonographic axial length measurements and OCT imaging. At study end, the animals were sacrificed and histomorphometric examinations of the retina and choroid were performed. We assessed the reproducibility of the OCT measurements and compared in-vivo measurements to histomorphometric data.Results: The mean thickness of the retina and choroid near the optic nerve head was 175.6 ± 25.8 and 63.4 ± 16.5 μm, respectively, and mean Bruch's membrane opening (BMO) diameter was 831 ± 121 μm. The intra-observer comparison of measurements of retinal thickness (intraclass correlation coefficient (ICC) = 0.92, 95% CI: 0.86–0.96; P &lt; 0.001), choroidal thickness (ICC = 0.92, 95% CI: 0.86–0.96; P &lt; 0.001), and BMO diameter (ICC = 0.92, 95% CI: 0.86–0.96; P &lt; 0.001) showed a high correlation. A high agreement was present also for the inter-observer reproducibility of the measurements of retinal thickness (Pearson correlation coefficient (R) = 0.98; P &lt; 0.001), choroidal thickness (R = 0.96; P &lt; 0.001), and BMO diameter (R = 0.98; P &lt; 0.001). The Bland-Altman plots showed that 2.6% (1/38), 5.3% (2/38), and 7.9% (3/38) of the measurement points of retinal thickness, choroidal thickness and BMO diameter, respectively, were located outside of the 95% limits of agreement. The OCT-based thickness measurements of retina and choroid were significantly higher than those measured by histomorphometry (both P-values &lt;0.01).Conclusion: OCT-based in-vivo morphometric imaging of the retina and choroid in guinea pigs is feasible with an acceptable intra-observer repeatability and inter-observer reproducibility.
Cost-Effectiveness of Conbercept vs. Ranibizumab for Age-Related Macular Degeneration, Diabetic Macular Edema, and Pathological Myopia: Population-Based Cohort Study and Markov Model
Authors: Cui Zhuang , Zhou Wei , Chang Qinxue , Zhang Tiantian , Wang Hui , Meng Xiangda , Liu Yuanyuan , Yan Hua 
Published: December 2021

Background: With the advent of aging society of China, fundus diseases related to pathological neovascularization, including age-related macular degeneration (AMD), diabetic macular edema (DME), and pathological myopia (PM), have become an increasingly serious medical and health problems. As effective drugs of the treatment, conbercept and ranibizumab have been commonly used and covered by the national basic medical insurance in China. However, the pharmacoeconomic evaluation of conbercept vs. ranibizumab for DME and PM remains lacking. This study would assess the cost-effectiveness of conbercept and ranibizumab for the treatment of AMD, DME, and PM from the perspective of Chinese payers.Methods: A Markov chain model was constructed based on the visual conditions of the patient indicated by the number of letters in best corrected visual acuity (BCVA). We conducted models based on real-world scenario to calculate the cost per the quality-adjusted life-year (QALY) gained. A 1-year cycle length and a 10-year simulation treatment were applied and the number of injections of conbercept and ranibizumab was assumed to the average number within 10 years. Transition probabilities, costs, utility data, and other parameters were obtained from literature searches. A 3.5% discounting rate was applied for both the costs and utilities.Results: The incremental cost-effectiveness ratios (ICERs) were more favorable for conbercept than ranibizumab in treatment of AMD, DME, and PM, with associated ICER of 66,669 renminbi (RMB), −258,813 RMB, and −373,185 RMB per QALY gained. Compared with ranibizumab, the incremental effectiveness of conbercept in treatment of AMD, DME, and PM was −0.665 QALYs, 0.215 QALYs, and 0.029 QALYs, respectively. The sensitivity analysis showed the same findings, although the ICER is sensitive to the costs of this program.Conclusion: Under the current Chinese healthcare setting, conbercept is suitable and cost-effective in treatment of AMD, DME, and PM compared with ranibizumab.
5-Methylcytosine RNA Methyltransferases-Related Long Non-coding RNA to Develop and Validate Biochemical Recurrence Signature in Prostate Cancer
Authors: Wang Ke , Zhong Weibo , Long Zining , Guo Yufei , Zhong Chuanfan , Yang Taowei , Wang Shuo , Lai Houhua , Lu Jianming , Zheng Pengxiang , Mao Xiangming 
Published: December 2021

The effects of 5-methylcytosine in RNA (m5C) in various human cancers have been increasingly studied recently; however, the m5C regulator signature in prostate cancer (PCa) has not been well established yet. In this study, we identified and characterized a series of m5C-related long non-coding RNAs (lncRNAs) in PCa. Univariate Cox regression analysis and least absolute shrinkage and selector operation (LASSO) regression analysis were implemented to construct a m5C-related lncRNA prognostic signature. Consequently, a prognostic m5C-lnc model was established, including 17 lncRNAs: MAFG-AS1, AC012510.1, AC012065.3, AL117332.1, AC132192.2, AP001160.2, AC129510.1, AC084018.2, UBXN10-AS1, AC138956.2, ZNF32-AS2, AC017100.1, AC004943.2, SP2-AS1, Z93930.2, AP001486.2, and LINC01135. The high m5C-lnc score calculated by the model significantly relates to poor biochemical recurrence (BCR)-free survival (p &lt; 0.0001). Receiver operating characteristic (ROC) curves and a decision curve analysis (DCA) further validated the accuracy of the prognostic model. Subsequently, a predictive nomogram combining the prognostic model with clinical features was created, and it exhibited promising predictive efficacy for BCR risk stratification. Next, the competing endogenous RNA (ceRNA) network and lncRNA–protein interaction network were established to explore the potential functions of these 17 lncRNAs mechanically. In addition, functional enrichment analysis revealed that these lncRNAs are involved in many cellular metabolic pathways. Lastly, MAFG-AS1 was selected for experimental validation; it was upregulated in PCa and probably promoted PCa proliferation and invasion in vitro. These results offer some insights into the m5C's effects on PCa and reveal a predictive model with the potential clinical value to improve the prognosis of patients with PCa.
Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis
Authors: Feng Xuelin , Song Zubiao , Wu Mengli , Liu Yanmei , Luo Sushan , Zhao Chongbo , Zhang Weixi 
Published: December 2021

Introduction: Approximately 10–20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic review and meta-analysis to explore the optimal therapies for refractory MG.Method: Correlative studies were performed through a search in PubMed, Cochrane Library, and Embase databases. The primary outcome was defined by changes in the quantitative myasthenia gravis score (QMG). Secondary outcomes were defined by the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Myasthenia Gravis Foundation of America (MGFA) post intervention status, adverse events, and disease exacerbation after treatment.Result: A total of 16 studies were included with 403 patients with refractory MG on therapies with rituximab, eculizumab, tacrolimus, and cladribine. Therapeutic efficacy of rituximab and eculizumab was identified with an estimated reduction in QMG score (4.158 vs. 6.928) and MG-ADL (4.400 vs. 4.344), respectively. No significant changes were revealed in efficacy or exacerbation density between the two independent therapeutic cohorts. The estimated adverse event density of eculizumab was more significant than that in the rituximab group (1.195 vs. 0.134 per patient-year), while the estimated serious event density was similar.Conclusion: The efficacy and safety of rituximab and eculizumab have been approved in patients with refractory MG. Rituximab had a superior safety profile than eculizumab with a lower incidence of adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236818, identifier CRD42021236818.
Effects of Neuromuscular Electrical Stimulation on Plantarflexors Spasticity, Gait Performance, and Self-Reported Health Outcomes in People With Chronic Stroke: A Study Protocol for a Double-Blinded Randomized Clinical Trial
Authors: Almutairi Sattam M. , Khalil Mohamed E. , Almutairi Nadiah , Alenazi Aqeel M. 
Published: December 2021

Introduction: Rehabilitation approaches have been used for people with stroke to decrease spasticity and improve functions, but little is known about the effect of neuromuscular electrical stimulation (NMES) in this population. Therefore, the primary purpose of this study was to establish a protocol for a double-blinded randomized clinical trial to examine using NMES on plantarflexors spasticity, dorsiflexor muscle strength, physical functions, and self-reported health outcomes in people with chronic stroke in Saudi Arabia.Material and Methods: This randomized clinical trial with two arms and double-blinded registered in ClinicalTrials (NCT04673045) will enroll 44 participants with chronic stroke and randomized them into either the experimental group (EG), including electrical stimulation (ES) with conventional therapy or the control sham group (NMESsham) including placebo electrical stimulation with conventional therapy. The frequency will be set at 80 Hz for 30 min. The intervention will be three times a week for 4 weeks for both groups. Data collection for pre- and post-intervention outcomes will include measurements for the primary outcomes including paretic limb (plantarflexor spasticity, ankle range of motion, and dorsiflexor muscles strength), and gait speed using 10-m walk test (10-MWT). The secondary outcomes including mobility function using Timed Up and Go (TUG), walking endurance using 6 Minutes Walk Test (6-MWT), activity of daily living using the Arabic version of Barthel Index (BI), and self-reported health measures such as quality of life using the Medical Outcomes Survey (Short Form 36, SF-36), physical activity using Rapid Assessment of Physical Activity (RAPA), depression symptoms using Patient Health Questionnaire-9 (PHQ-9), fatigue level using Fatigue Severity Scale (FSS), and risk of fall using Fall Efficacy Scale International (FES-I). An independent t-test will be utilized to examine the effect of the intervention on the outcome measures.Results: The recruitment has started and is ongoing.Conclusions: Using 4 weeks of NMES will provide information about its effect in improving plantarflexor spasticity, dorsiflexor muscles strength, gait speed, mobility functions, and other self-reported health outcomes in people with chronic stroke when compared to NMESsham.