bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and verification of IGFBP3 and YTHDC1 as biomarkers associated with immune infiltration and mitophagy in hypertrophic cardiomyopathy
Authors: Li Yao , Zhang Wei , Dai Yan , Chen Keping 
Published: October 2022

Background: Hypertrophic cardiomyopathy (HCM) is the main cause of sudden cardiac death among young adults, yet its pathogenesis remains vague. N6-methyladenosine (m6A) methylation modification was involved in various cardiovascular diseases such as coronary heart disease and heart failure, although its influence on HCM remains unclear. This study aimed to explore the potential role of m6A in the diagnosis and pathogenesis of HCM.Methods: GSE36961 including 106 HCM and 39 controls was used in the study. The HCM-related m6A regulators were selected using support vector machine recursive feature elimination and random forest algorithm. A significant gene signature was then established using least absolute shrinkage and selection operator and then verified by GSE130036. Subgroup classification of HCM was performed based on the expression of m6A biomarkers. Gene set variation analysis was employed to explore the functional difference between distinct subgroups. Weighted gene co-expression network analysis was used to determine the m6A-related hub module. Single-sample gene set enrichment analysis was conducted to assess the immune and mitophagy features between subgroups. Besides, transfection of recombinant plasmids with targeted genes into H9c2 cells was performed to further verify the function of the significant biomarkers.Results: Significant difference existed in m6A landscape between HCM and control patients, among which IGFBP3 and YTHDC1 were identified as the independent biomarkers of HCM. Highly infiltrated immune cells (MDSC, macrophages, etc.), more enriched immune-related pathways (TNFα signaling via NFκB and IL6-JAK-STAT3 signaling) and cardiac remodeling-associated pathways (epithelial mesenchymal transition, angiogenesis, etc.) were identified in the subgroup with higher IGFBP3. Consistently, overexpression of IGFBP3 in H9c2 cells led to upregulation of extracellular-matrix-related genes (COL1A2, COL3A1 and MMP9) and inflammation-related genes (TNFα and IL6). Besides, higher YTHDC1 expression seemed to be consistent with less-activated mitophagy (PINK1-PRKN mediated mitophagy) and energy metabolism. Further experiments demonstrated that overexpression of YTHDC1 resulted in up-regulation of PINK and PRKN in cardiomyocytes, which are essential genes mediating mitophagy.Conclusion: Two m6A readers (IGFBP3 and YTHDC1) well distinguished HCM and may facilitate clinical diagnosis. IGFBP3 may play a role in the immune-microenvironments and remodeling of cardiac tissues, while YTHDC1 may influence mitophagy and energy metabolism in HCM.
MiR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF
Authors: Wang Yunwei , Li Ming , Zeng Jiaoxia , Yang Yunshu , Li Zengshan , Hu Sijun , Yang Fangfang , Wang Na , Wang Wenlan , Tie Jun 
Published: October 2022

BackgroundGastric cancer (GC) is one of the most malignant and lethal cancers worldwide. Multiple microRNAs (miRNAs) have been identified as key regulators in the progression of GC. However, the underlying pathogenesis that miRNAs govern GC malignancy remains uncertain. Here, we identified a novel miR-585-5p as a key regulator in GC development.MethodsThe expression of miR-585-5p in the context of GC tissue was detected by in situ hybridization for GC tissue microarray and assessed by H-scoring. The gain- and loss-of-function analyses comprised of Cell Counting Kit-8 assay and Transwell invasion and migration assay. The expression of downstream microphthalmia-associated transcription factor (MITF), cyclic AMP-responsive element-binding protein 1 (CREB1) and mitogen-activated protein kinase 1 (MAPK1) were examined by Immunohistochemistry, quantitative real-time PCR and western blot. The direct regulation between miR-585-5p and MITF/CREB1/MAPK1 were predicted by bioinformatic analysis and screened by luciferase reporter assay. The direct transcriptional activation of CREB1 on MITF was verified by luciferase reporter assay, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs). The interaction between MAPK1 and MITF was confirmed by co-immunoprecipitation (Co-IP) and immunofluorescent double-labelled staining.ResultsMiR-585-5p is progressively downregulated in GC tissues and low miR-585-5p levels were strongly associated with poor clinical outcomes. Further gain- and loss-of-function analyses showed that miR-585-5p possesses strong anti-proliferative and anti-metastatic capacities in GC. Follow-up studies indicated that miR-585-5p targets the downstream molecules CREB1 and MAPK1 to regulate the transcriptional and post-translational regulation of MITF, respectively, thus controlling its expression and cancer-promoting activity. MiR-585-5p directly and negatively regulates MITF together with CREB1 and MAPK1. According to bioinformatic analysis, promotor reporter gene assays, ChIP and EMSAs, CREB1 binds to the promotor region to enhance transcriptional expression of MITF. Co-IP and immunofluorescent double-labelled staining confirmed interaction between MAPK1 and MITF. Protein immunoprecipitation revealed that MAPK1 enhances MITF activity via phosphorylation (Ser73). MiR-585-5p can not only inhibit MITF expression directly, but also hinder MITF expression and pro-cancerous activity in a CREB1-/MAPK1-dependent manner indirectly.ConclusionsIn conclusion, this study uncovered miR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF.
Role of N-acetylcysteine treatment in women with advanced age undergoing IVF/ICSI cycles: A prospective study
Authors: Li Xiufang , Wang Zhongqing , Wang Huidan , Xu Haiyan , Sheng Yan , Lian Fang 
Published: October 2022

ObjectiveThe main objective of this study was to explore the efficacy of a new antioxidant N-acetylcysteine (NAC) supplementation in reproductive outcomes of advanced age women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET), and the effect on the expression of L-glutathione (GSH) in follicular fluid (FF) and mitochondrial DNA (mtDNA) copy number of granulosa cells.MethodsThe present prospective randomized controlled study was conducted in 200 patients with advanced age women undergoing GnRH antagonist protocol. The treatment group (group A) consisted of 100 women who received N-acetylcysteine treatment from the menstrual phase of the previous cycle for about 45 days using the GnRH antagonist protocol. The control group (group B) consisted of 100 women who received the same protocol without N-acetylcysteine. Total gonadotrophin dosage the number of oocyte received, high-quality blastocysts, and pregnancy outcomes were compared between two groups. Pregnancy outcomes included biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate, ectopic pregnancy rate, multiple pregnancy rate, and ongoing pregnancy rate. Follicular fluid (FF) was collected after oocytes were gathered. The GSH content in the FF was tested with enzyme linked immunosorbent assay (ELISA). The mtDNA copy number of the granulosa cells was measured using real-time PCR techniques.ResultsTotal doses of Gn in the NAC treatment group were less than those in the control group (2385.50 ± 879.19 vs. 2527.63 ± 1170.33, P = 0.047). Compared with the control, the number of high-quality blastocysts in NAC treatment increased significantly (1.82 ± 2.12 vs. 1.43 ± 1.58, p = 0.014). Clinical pregnancy rates did not differ in both groups (all P &gt; 0.05). At the same time, the GSH content in the FF differed significantly between the two groups (1.88 ± 1.23 vs. 1.07 ± 0.70, p = 0.001). There was no significant difference in the mtDNA copy number between the two groups (P = 0.157).ConclusionA combination of NAC and Gn treatment is capable of improving the ovarian response to superovulation drugs in assisted reproductive technologies (ARTs) and also in aged populations. The addition of NAC during IVF can improve the quality of blastocysts in advanced age female subjects. However, more clinical trials are required to be designed to confirm this conclusion in future.Ethics and disseminationThe experiment solicited approval from the Institutional ethics committee of the Affiliated Reproductive Hospital of Shandong University. All the participants provided written informed consent. This survey was conducted as per the Declaration of Helsinki and relevant amendments.Trial registration numberwww.chictr.org.cn, identifier ChiCTR2100048297.
The effectiveness and safety of the rapid titration strategy of background controlled-release oxycodone hydrochloride for patients with moderate-to-severe cancer pain: A retrospective cohort study
Authors: Feng Weineng , Wang Yufeng , Ran Fengming , Mao Yong , Zhang Helong , Wang Qifeng , Lin Wen , Wang Zhidong , Hu Jianli , Liao Wangjun , Zhang Tao , Chu Qian , Xiong Weijie , Yi Tienan , Yi Jiqun , Ma Shoucheng , Sun Yi , Meng Lingzhan , Liu Chunling , Zhou Silang , Zheng Dengyun , Wang Shubin , Lin Haifeng , Fang Wenzheng , Li Jun , Wu Minhui 
Published: October 2022

BackgroundOxycodone hydrochloride is a semisynthetic narcotic analgesic agent. This study aimed to explore optimal titration strategy of controlled-release (CR) oxycodone hydrochloride in patients with cancer pain.Methods258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied. The patients were divided into 4 groups according to treatment regimens titrated. The pain remission rate and numeric rating scale (NRS) of cancer pain was recorded at 0, 12, 24, 36, 48, 60, 72 h after opioid titration. The incidence of adverse events (AEs) with therapy were also observed.Results12 h after treatment, pain remission rate of Group B, C and D was significantly higher (P &lt; 0.001) than Group A. For the complete remission rate, there were also significant differences among the four groups (P &lt; 0.001). No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P &lt; 0.01), with the most frequent AEs in Group A, lowest in Group B.ConclusionThe rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain.
Case report: Endovascular embolization of a cerebral pseudoaneurysm caused by SARS-CoV2 infection
Authors: García-Carmona Juan Antonio , von Quednow Enzo , Hernández-Fernández Francisco , Molina-Nuevo Juan David , García-García Jorge , Palao María , Segura Tomás 
Published: October 2022

BackgroundSevere COVID-19 has been shown to produce convulsions, encephalitis, Guillain-Barré syndrome, or cerebrovascular disease. However, only 4 case reports described subarachnoid or brain hemorrhage caused by ruptured cerebral aneurysms or pseudoaneurysms in patients with COVID-19. Cerebral pseudoaneurysms represent &lt;1% of all intracranial aneurysms and have been related to radiation therapy, vasculitis, rupture of true saccular aneurysms, arteriovenous malformations, and infections by bacteria and viruses, such as Epstein-Bar and Herpes virus.Case presentationA 28-year-old Caucasian woman, with no medical history of interest and completely vaccinated against SARS-CoV-2, was admitted to Neurology due to progressive tetraparesis with areflexia, a cough, and a fever of 38°C. SARS-CoV2 PCR was positive while lumbar puncture, blood tests, and electromyogram showed criteria for Guillain-Barré syndrome. Despite the treatment, the patient developed dyspnea and tetraplegia requiring invasive mechanical ventilation. There was motor neurological improvement but a decreased level of consciousness was observed on day 13. A brain CT scan demonstrated an acute haematoma and cerebral arteriography showed a 4-mm pseudoaneurysm located in a branch of the left middle cerebral artery. Given the high risk of rebleeding, endovascular treatment was decided upon. Therefore, complete embolization of the pseudoaneurysm was carried out by using the synthetic glue N-butyl-cyanocrylate. Two days later, the patient was clinically and neurologically recovered and was discharged. Lastly, a new angiography showed no evidence of the pseudoaneurysm 3-weeks later.ConclusionsWe report, for the first time, a patient suffering a severe immune reaction caused by SARS-CoV2 infection and developing a cerebral pseudoaneurysm treated with endovascular embolization without complications.
Aberrant interhemispheric functional reciprocities of the default mode network and motor network in subcortical ischemic stroke patients with motor impairment: A longitudinal study
Authors: Li Yongxin , Yu Zeyun , Zhou Xuan , Wu Ping , Chen Jiaxu 
Published: October 2022

PurposeThe purpose of the present study was to explore the longitudinal changes in functional homotopy in the default mode network (DMN) and motor network and its relationships with clinical characteristics in patients with stroke.MethodsResting-state functional magnetic resonance imaging was performed in stroke patients with subcortical ischemic lesions and healthy controls. The voxel-mirrored homotopic connectivity (VMHC) method was used to examine the differences in functional homotopy in patients with stroke between the two time points. Support vector machine (SVM) and correlation analyses were also applied to investigate whether the detected significant changes in VMHC were the specific feature in patients with stroke.ResultsThe patients with stroke had significantly lower VMHC in the DMN and motor-related regions than the controls, including in the precuneus, parahippocampus, precentral gyrus, supplementary motor area, and middle frontal gyrus. Longitudinal analysis revealed that the impaired VMHC of the superior precuneus showed a significant increase at the second time point, which was no longer significantly different from the controls. Between the two time points, the changes in VMHC in the superior precuneus were significantly correlated with the changes in clinical scores. SVM analysis revealed that the VMHC of the superior precuneus could be used to correctly identify the patients with stroke from the controls with a statistically significant accuracy of 81.25% (P ≤ 0.003).ConclusionsOur findings indicated that the increased VMHC in the superior precuneus could be regarded as the neuroimaging manifestation of functional recovery. The significant correlation and the discriminative power in classification results might provide novel evidence to understand the neural mechanisms responsible for brain reorganization after stroke.
Vibrotactile enhancement in hand rehabilitation has a reinforcing effect on sensorimotor brain activities
Authors: Du Qiang , Luo Jingjing , Cheng Qiying , Wang Youhao , Guo Shijie 
Published: October 2022

ObjectiveStroke patients often suffer from hand dysfunction or loss of tactile perception, which in turn interferes with hand rehabilitation. Tactile-enhanced multi-sensory feedback rehabilitation is an approach worth considering, but its effectiveness has not been well studied. By using functional near-infrared spectroscopy (fNIRS) to analyze the causal activity patterns in the sensorimotor cortex, the present study aims to investigate the cortical hemodynamic effects of hand rehabilitation training when tactile stimulation is applied, and to provide a basis for rehabilitation program development.MethodsA vibrotactile enhanced pneumatically actuated hand rehabilitation device was tested on the less-preferred hand of 14 healthy right-handed subjects. The training tasks consisted of move hand and observe video (MO), move hand and vibration stimulation (MV), move hand, observe video, and vibration stimulation (MOV), and a contrast resting task. Region of interest (ROI), a laterality index (LI), and causal brain network analysis methods were used to explore the brain’s cortical blood flow response to a multi-sensory feedback rehabilitation task from multiple perspectives.Results(1) A more pronounced contralateral activation in the right-brain region occurred under the MOV stimulation. Rehabilitation tasks containing vibrotactile enhancement (MV and MOV) had significantly more oxyhemoglobin than the MO task at 5 s after the task starts, indicating faster contralateral activation in sensorimotor brain regions. (2) Five significant lateralized channel connections were generated under the MV and MOV tasks (p &lt; 0.05), one significant lateralized channel connection was generated by the MO task, and the Rest were not, showing that MV and MOV caused stronger lateralization activation. (3) We investigated all thresholds of granger causality (GC) resulting in consistent relative numbers of effect connections. MV elicited stronger causal interactions between the left and right cerebral hemispheres, and at the GC threshold of 0.4, there were 13 causal network connection pairs for MV, 7 for MO, and 9 for MOV.ConclusionVibrotactile cutaneous stimulation as a tactile enhancement can produce a stronger stimulation of the brain’s sensorimotor brain areas, promoting the establishment of neural pathways, and causing a richer effect between the left and right cerebral hemispheres. The combination of kinesthetic, vibrotactile, and visual stimulation can achieve a more prominent training efficiency from the perspective of functional cerebral hemodynamics.
Comparison of complications and long-term survival after minimally invasive esophagectomy versus open esophagectomy in patients with esophageal cancer and chronic obstructive pulmonary disease
Authors: Rong Yu , Hao Yanbing , Xue Jun , Li Xiaoyuan , Li Qian , Wang Li , Li Tian 
Published: October 2022

ObjectiveTo compare the complications and long-term survival of esophageal cancer patients with chronic obstructive pulmonary disease (COPD) after minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) using propensity score matching (PSM).MethodsEsophageal cancer patients who underwent esophagectomy at the Thoracic Surgery Department of the First Affiliated Hospital of Hebei North University from January 2010 to December 2018 were retrospectively enrolled. The incidence of postoperative complications and prognosis of the MIE (n = 132) and OE (n = 138) groups were compared. To reduce bias, 1:1 PSM was adopted for the analysis.ResultsThe median disease-free survival (DFS) of the MIE and OE groups were 24 months and 26 months, respectively, and neither group reached median survival. There was no significant difference between the two groups in terms of 3-year DFS and overall survival (OS). The stratification of the patients on the basis of the percentage of estimated forced expiratory volume in the first second (%FEV1) did not result in significant differences in the survival rates. A total of 42 patients (50%) in the MIE group and 55 patients (65.48%) in the OE group experienced complications, and the difference was statistically significant (OR=0.527, 95% CI: 0.283–0.981, P=0.042). The incidence of acute COPD exacerbation (OR=0.213, 95% OR, CI: 0.068–0.666, P=0.004) and pulmonary atelectasis requiring bronchoscopic aspiration (OR=0.232, 95% OR, CI: 0.082–0.659, P=0.004) were significantly higher in the OE versus the MIE group. In addition, the distribution of the various grades of complications also differed significantly between the two groups (P=0.016). While the incidence of minor complications (≤Grade II) was similar in both groups (P=0.503), that of severe complications (≥Grade III) was markedly higher in the OE group (P=0.002) and the Grade-IIIa complications were predominant (P=0.001). The severity of complications was correlated with the postoperative duration of hospital stay in both groups (r=0.187, P=0.015). No significant difference was observed in the incidence of minor complications (≤Grade II) between the two groups following stratification on the basis of %FEV1, whereas severe complications were more frequent in the OE group among patients with %FEV1 between 60% and 70% (P=0.001&lt;0.05).ConclusionThere was no significant difference in the postoperative DFS and OS of esophageal cancer patients with COPD after undergoing MIE or OE. However, MIE significantly reduced the incidence of severe postoperative complications among patients with %FEV1 between 60% and 70%.
Knowledge-based planning for multi-isocenter VMAT total marrow irradiation
Authors: Ahn Kang-Hyun , Rondelli Damiano , Koshy Matthew , Partouche Julien A. , Hasan Yasmin , Liu Hongtao , Yenice Kamil , Aydogan Bulent 
Published: October 2022

PurposeTotal marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges.MethodsFifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model.ResultsKBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03).ConclusionsKBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.