bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of an m6A RNA Methylation Regulators-Based Signature for Predicting the Prognosis of Adrenocortical Carcinoma
Authors: Shen Chengquan , Liu Jing , Yang Xiaokun , Jiao Wei , Wang Yonghua 
Published: February 2021

BackgroundAdrenocortical carcinoma (ACC) is an aggressive and rare neoplasm that originates from the cortex of the adrenal gland. N6-methyladenosine (m6A) RNA methylation, the most common form of mRNA modification, has been reported to be correlated with the occurrence and development of the malignant tumor. This study aims to identify the significance of m6A RNA methylation regulators in ACC and construct a m6A based signature to predict the prognosis of ACC patients.Materials and methodsRNA-seq data from The Cancer Genome Atlas (TCGA) database was used to identify the expression level of m6A RNA methylation regulators in ACC. An m6A based signature was further constructed and its prognostic and predictive values were assessed by survival analysis and nomogram.Results11 m6A RNA regulators were differentially expressed in ACC and three m6A RNA regulators were finally selected in a signature to predict the prognosis of ACC patients. Survival analysis indicated that high risk scores were closely related to poor survival outcomes in ACC patients. Univariate and multivariate Cox regression analyses demonstrated that the m6A based signature was an independent prognostic factor for ACC patients. A nomogram with clinical factors and the m6A based signature was also constructed to superiorly predict the prognosis of ACC patients. The expression levels of m6A RNA methylation regulators, which were contained in the signature, were also verified in human ACC tissues and normal tissues by using vitro experiments.ConclusionWe identified and validated an m6A based signature, which can be used as an independent prognostic factor in evaluating the prognosis of ACC patients. Further clinical trials and experimental explorations are needed to confirm our observations and mechanisms underlying prognostic values of these m6A RNA methylation regulators in ACC.
A Novel Six-Gene-Based Prognostic Model Predicts Survival and Clinical Risk Score for Gastric Cancer
Authors: Li Juan , Pu Ke , Li Chunmei , Wang Yuping , Zhou Yongning 
Published: February 2021

Background:Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related genes (ARGs) have rarely been analyzed in gastric cancer (GC). The purpose of this study was to analyze ARGs in GC using bioinformatic analysis and to identify new biomarkers for predicting the overall survival (OS) of patients with GC.Methods:The gene expression profiles and clinical data of patients with GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and ARGs were obtained from two other datasets (the Human Autophagy Database and Molecular Signatures Database). Lasso, univariate, and multivariate Cox regression analyses were performed to identify the OS-related ARGs. Finally, a six-ARG model was identified as a prognostic indicator using the risk-score model, and survival and prognostic performance were analyzed based on the Kaplan-Meier test and ROC curve. Estimate calculations were used to assess the immune status of this model, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed for investigating the functions and terms associated with the model-related genes in GC.Results:The six ARGs,DYNLL1,PGK2,HPR,PLOD2,PHYHIP, andCXCR4, were identified using Lasso and Cox regression analyses. Survival analysis revealed that the OS of GC patients in the high-risk group was significantly lower than that of the low-risk group (p&lt; 0.05). The ROC curves revealed that the risk score model exhibited better prognostic performance with respect to OS. Multivariate Cox regression analysis indicated that the model was an independent predictor of OS and was not affected by most of the clinical traits (p&lt; 0.05). The model-related genes were associated with immune suppression and several biological process terms, such as extracellular structure organization and matrix organization. Moreover, the genes were associated with the P13K-Akt signaling pathway, focal adhesion, and MAPK signaling pathway.Conclusions:This study presents potential prognostic biomarkers for GC patients that would aid in determining the best patient-specific course of treatment.
Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels
Authors: Gill Erin E. , Smith Maren L. , Gibson Kristen M. , Morishita Kimberly A. , Lee Amy H. Y. , Falsafi Reza , Graham Jinko , Foell Dirk , Benseler Susanne M. , Ross Colin J. , Luqmani Raashid A. , Cabral David A. , Hancock Robert E. W. , Brown Kelly L. ,   The PedVas Initiative Investigators
Published: February 2021

Objectives: Chronic primary vasculitis describes a group of complex and rare diseases that are characterized by blood vessel inflammation. Classification of vasculitis subtypes is based predominantly on the size of the involved vessels and clinical phenotype. There is a recognized need to improve classification, especially for small-to-medium sized vessel vasculitides, that, ideally, is based on the underlying biology with a view to informing treatment.Methods: We performed RNA-Seq on blood samples from children (n = 41) and from adults (n = 11) with small-to-medium sized vessel vasculitis, and used unsupervised hierarchical clustering of gene expression patterns in combination with clinical metadata to define disease subtypes.Results: Differential gene expression at the time of diagnosis separated patients into two primary endotypes that differed in the expression of ~3,800 genes in children, and ~1,600 genes in adults. These endotypes were also present during disease flares, and both adult and pediatric endotypes could be discriminated based on the expression of just 20 differentially expressed genes. Endotypes were associated with distinct biological processes, namely neutrophil degranulation and T cell receptor signaling.Conclusions: Phenotypically similar subsets of small-to-medium sized vessel vasculitis may have different mechanistic drivers involving innate vs. adaptive immune processes. Discovery of these differentiating immune features provides a mechanistic-based alternative for subclassification of vasculitis.
Effect of High-Flow Oxygen on Exercise Performance in COPD Patients. Randomized Trial
Authors: Bitos Konstantinos , Furian Michael , Mayer Laura , Schneider Simon R. , Buenzli Simone , Mademilov Maamed Z. , Sheraliev Ulan U. , Marazhapov Nuridin H. , Abdraeva Ainura K. , Aidaralieva Shoira D. , Muratbekova Aybermet M. , Sooronbaev Talant M. , Ulrich Silvia , Bloch Konrad E. 
Published: February 2021

Background: High-flow oxygen therapy (HFOT) provides oxygen-enriched, humidified, and heated air at high flow rates via nasal cannula. It could be an alternative to low-flow oxygen therapy (LFOT) which is commonly used by patients with chronic obstructive pulmonary disease (COPD) during exercise training.Research Question: We evaluated the hypothesis that HFOT improves exercise endurance in COPD patients compared to LFOT.Methods: Patients with stable COPD, FEV1 40–80% predicted, resting pulse oximetry (SpO2) ≥92%, performed two constant-load cycling exercise tests to exhaustion at 75% of maximal work rate on two different days, using LFOT (3 L/min) and HFOT (60 L/min, FiO2 0.45) in randomized order according to a crossover design. Primary outcome was exercise endurance time, further outcomes were SpO2, breath rate and dyspnea.Results: In 79 randomized patients, mean ± SD age 58 ± 9 y, FEV1 63 ± 9% predicted, GOLD grades 2-3, resting PaO2 9.4 ± 1.0 kPa, intention-to-treat analysis revealed an endurance time of 688 ± 463 s with LFOT and 773 ± 471 s with HFOT, mean difference 85 s (95% CI: 7 to 164, P = 0.034), relative increase of 13% (95% CI: 1 to 28). At isotime, patients had lower respiratory rate and higher SpO2 with HFOT. At end-exercise, SpO2 was higher by 2% (95% CI: 2 to 2), and Borg CR10 dyspnea scores were lower by 0.8 points (95% CI: 0.3 to 1.2) compared to LFOT.Interpretation: In mildly hypoxemic patients with COPD, HFOT improved endurance time in association with higher arterial oxygen saturation, reduced respiratory rate and less dyspnea compared to LFOT. Therefore, HFOT is promising for enhancing exercise performance in COPD.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03955770.
Assessment of Image Quality and Lesion Detectability With Digital PET/CT System
Authors: Delcroix Olivier , Bourhis David , Keromnes Nathalie , Robin Philippe , Le Roux Pierre-Yves , Abgral Ronan , Salaun Pierre-Yves , Querellou Solène 
Published: February 2021

Purpose: The aim of this study was to assess image quality and lesion detectability acquired with a digital Positron Emission Tomography/Computed Tomography (PET/CT) Siemens Biograph Vision 600 system.Material and Methods: Consecutive patients who underwent a FDG PET/CT during the first week of use of a digital PET/CT (Siemens Biograph Vision 600) at the nuclear medicine department of the university hospital of Brest were analyzed. PET were realized using list mode acquisition. For all patients, 4 datasets were reconstructed. We determined, according to phantom measurements, an equivalent time acquisition/reconstruction parameters pair of the digital PET/CT corresponding to an analog PET/CT image quality (“analog-like”) as reference dataset. We compared the reference dataset with 3 others digital PET/CT reconstruction parameters, allowing a decrease of emission duration: 60, 90, and 120 s per bed position. Three nuclear medicine physicians evaluated independently, for each dataset, overall image quality [Maximal Intensity Projection (MIP), noise, sharpness] using a 4-point scale. Physicians assessed also lesion detection capability by reporting new visible lesions on each digital datasets with their confidence level in comparison with analog-like dataset.Results: Ninety-eight patients were analyzed. Image quality of MIP (IQMIP), sharpness (IQSHARPNESS), and noise (IQNOISE) of all digital datasets (60, 90, and 120 s) were better than those evaluated with analog-like reconstruction. Moreover, digital PET/CT system improved IQMIP, IQNOISE, and IQSHARPNESS whatever the BMI. Lesion detection capability and confidence level were higher for 60, 90, 120 s per bed position, respectively, than for analog-like images.Conclusion: Our study demonstrated an improvement of image quality and lesion detectability with a digital PET/CT system.
Early Treatment Initiation With Oral Prednisolone for Relapse Prevention Alleviates Depression and Fatigue in Aquaporin-4–Positive Neuromyelitis optica Spectrum Disorder
Authors: Akaishi Tetsuya , Takahashi Toshiyuki , Fujihara Kazuo , Misu Tatsuro , Fujimori Juichi , Takai Yoshiki , Nishiyama Shuhei , Abe Michiaki , Ishii Tadashi , Aoki Masashi , Nakashima Ichiro 
Published: February 2021

Background:Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune-related neurological disorder of the central nervous system. Most patients with NMOSD have serum anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). In addition to optic neuritis and myelitis, other insidious symptoms such as depressive state and chronic fatigue in NMOSD are gradually being recognized.Methods: To elucidate the impact of low- to medium-dose oral prednisolone (PSL) as a relapse prevention therapy for psychiatric disturbances and chronic fatigue in NMOSD, we evaluated clinical data from 39 patients with AQP4-IgG-positive NMOSD, along with the details of present and cumulative oral PSL dosage.Results: Thirty-six of the 39 patients were treated with low- to medium-dose oral PSL, and the mean and standard deviation of the present daily dose of oral PSL were 7.9 ± 4.0 mg/day. None of the patients were treated with a daily PSL dose of &gt;15 mg. As a result, the disease duration and the untreated period before starting oral PSL showed weak to moderate correlations with the subsequent severities of psychiatric disturbance and fatigue level. Meanwhile, none of the other treatment-related variables evaluated, such as the present oral PSL daily dose, cumulative PSL dose, months of oral PSL administration, previous courses of steroid pulse therapy, and coadministered immunosuppressants, were correlated with these insidious symptoms.Conclusion: Our results suggest that the use of long-term low- to medium-dose oral PSL ≤15 mg daily for relapse prevention in AQP4-IgG-positive NMOSD would not aggravate the psychiatric and fatigue conditions. On the contrary, early initiation of oral PSL for relapse prevention, together with significantly decreased relapse rate, alleviated the subsequent depressive state and fatigue from the disease.
CT Angiography-Based Radiomics for Classification of Intracranial Aneurysm Rupture
Authors: Alwalid Osamah , Long Xi , Xie Mingfei , Yang Jiehua , Cen Chunyuan , Liu Huan , Han Ping 
Published: February 2021

Background: Intracranial aneurysm rupture is a devastating medical event with a high morbidity and mortality rate. Thus, timely detection and management are critical. The present study aimed to identify the aneurysm radiomics features associated with rupture and to build and evaluate a radiomics classification model of aneurysm rupture.Methods: Radiomics analysis was applied to CT angiography (CTA) images of 393 patients [152 (38.7%) with ruptured aneurysms]. Patients were divided at a ratio of 7:3 into retrospective training (n = 274) and prospective test (n = 119) cohorts. A total of 1,229 radiomics features were automatically calculated from each aneurysm. The feature number was systematically reduced, and the most important classifying features were selected. A logistic regression model was constructed using the selected features and evaluated on training and test cohorts. Radiomics score (Rad-score) was calculated for each patient and compared between ruptured and unruptured aneurysms.Results: Nine radiomics features were selected from the CTA images and used to build the logistic regression model. The radiomics model has shown good performance in the classification of the aneurysm rupture on training and test cohorts [area under the receiver operating characteristic curve: 0.92 [95% confidence interval CI: 0.89–0.95] and 0.86 [95% CI: 0.80–0.93], respectively, p &lt; 0.001]. Rad-score showed statistically significant differences between ruptured and unruptured aneurysms (median, 2.50 vs. −1.60 and 2.35 vs. −1.01 on training and test cohorts, respectively, p &lt; 0.001).Conclusion: The results indicated the potential of aneurysm radiomics features for automatic classification of aneurysm rupture on CTA images.
Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience
Authors: Lin Sheng-Feng , Hu Han-Hwa , Ho Bo-Lin , Chen Chih-Hung , Chan Lung , Lin Huey-Juan , Sun Yu , Lin Yung-Yang , Chen Po-Lin , Lin Shinn-Kuang , Wei Cheng-Yu , Lin Yu-Te , Lee Jiunn-Tay , Chao A-Ching ,   Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group
Published: February 2021

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT).Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes.Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28–18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01–25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0–1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0–2 (adjusted OR: 1.39, 95% CI, 0.97–1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77–12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT.Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.
Age-Related Cognitive Decline and the Olfactory Identification Deficit Are Associated to Increased Level of Depression
Authors: Sanna Fabrizio , Loy Francesco , Piras Raffaella , Moat Alan , Masala Carla 
Published: February 2021

PurposePrevious studies reported a correlation between olfactory function and depression. However, in literature, no data are available for the correlation between depression and all other factors such as age, sex, olfactory, gustatory, and cognitive function in healthy subjects taken together. The aim of this study was to provide a systematic account regarding the association between those variables in a non-clinical population.MethodsTwo hundred and seventy-three participants were recruited with an age range of 19–84 years. Olfactory, gustatory, cognitive function, and depression level were evaluated by means of the following tests: the Sniffin’ Sticks test, Taste Strips test, Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI).ResultsIn our data, an age-related decrease in olfactory and gustatory function and a decline in cognitive functions such as attention, memory, and language were observed. Instead, no significant differences were observed for the depression level in relation to the different age ranges. However, our results indicated that the depression level could be associated to sex, odor identification impairment, and decreased attention and language.ConclusionSex, the odor identification impairment, and an age-related decrease in attention and language are associated with increased level of depression in healthy subjects. Our data can be useful and informative for health care workers, that is, to have adequate preventive strategies to be used whenever these conditions are detected and recognized.
Efficacy of BRAF Inhibitors in Combination With Stereotactic Radiosurgery for the Treatment of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis
Authors: Khan Muhammad , Zheng Tao , Zhao Zhihong , Arooj Sumbal , Liao Guixiang 
Published: February 2021

BackgroundBRAF inhibitors have improved the outcome for patients with BRAF mutant metastatic melanoma and have shown intracranial responses in melanoma brain metastases. Stereotactic radiosurgery (SRS) is being used as a local treatment for melanoma brain metastasis (MBM) with better local control and survival. We searched for studies comparing the combination of two treatments with SRS alone to detect any clinical evidence of synergism.Materials and MethodsPubMed, EMBASE, Medline, and Cochrane library were searched until May 2020 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included survival as the primary, and local control as the secondary outcome.ResultsA total of eight studies involving 976 patients with MBM were selected. Survival was significantly improved for patients receiving BRAF inhibitor plus SRS in comparison to SRS alone as assessed from the time of SRS induction (SRS survival: hazard ratio [HR] 0.67 [0.58–0.79], p &lt;0.00001), from the time of brain metastasis diagnosis (BM survival: HR 0.65 [0.54, 0.78], p &lt; 0.00001), or from the time of primary diagnosis (PD survival: HR 0.74 [0.57–0.95], p = 0.02). Dual therapy was also associated with improved local control, indicating an additive effect of the two treatments (HR 0.53 [0.31–0.93], p=0.03). Intracranial hemorrhage was higher in patients receiving BRAF inhibitors plus SRS than in those receiving SRS alone (OR, 3.16 [1.43–6.96], p = 0.004).ConclusionsBRAF inhibitors in conjunction with SRS as local treatment appear to be efficacious. Local brain control and survival improved in patients with MBM receiving dual therapy. Safety assessment would need to be elucidated further as the incidence of intracranial hemorrhage was increased.
A Novel Treatment Concept for Advanced Stage Mandibular Osteoradionecrosis Combining Isodose Curve Visualization and Nerve Preservation: A Prospective Pilot Study
Authors: van Baar Gustaaf J. C. , Leeuwrik Lars , Lodders Johannes N. , Liberton Niels P. T. J. , Karagozoglu K. Hakki , Forouzanfar Tymour , Leusink Frank K. J. 
Published: February 2021

BackgroundOsteoradionecrosis (ORN) of the mandible is a severe complication of radiation therapy in head and neck cancer patients. Treatment of advanced stage mandibular osteoradionecrosis may consist of segmental resection and osseous reconstruction, often sacrificing the inferior alveolar nerve (IAN). New computer-assisted surgery (CAS) techniques can be used for guided IAN preservation and 3D radiotherapy isodose curve visualization for patient specific mandibular resection margins. This study introduces a novel treatment concept combining these CAS techniques for treatment of advanced stage ORN.MethodsOur advanced stage ORN treatment concept includes consecutively: 1) determination of the mandibular resection margins using a 3D 50 Gy isodose curve visualization, 2) segmental mandibular resection with preservation of the IAN with a two-step cutting guide, and 3) 3D planned mandibular reconstruction using a hand-bent patient specific reconstruction plate. Postoperative accuracy of the mandibular reconstruction was evaluated using a guideline. Objective and subjective IAN sensory function was tested for a period of 12 months postoperatively.ResultsFive patients with advanced stage ORN were treated with our ORN treatment concept using the fibula free flap. A total of seven IANs were salvaged in two men and three women. No complications occurred and all reconstructions healed properly. Neither non-union nor recurrence of ORN was observed. Sensory function of all IANs recovered after resection up to 100 percent, including the patients with a pathologic fracture due to ORN. The accuracy evaluation showed angle deviations limited to 3.78 degrees. Two deviations of 6.42° and 7.47° were found. After an average of 11,6 months all patients received dental implants to complete oral rehabilitation.ConclusionsOur novel ORN treatment concept shows promising results for implementation of 3D radiotherapy isodose curve visualization and IAN preservation. Sensory function of all IANs recovered after segmental mandibular resection.