bluuebunny/crossref_metadata_2025_split huggingface dataset:
YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway
Authors: Shen Xudong , Zhao Kui , Xu Liming , Cheng Guilian , Zhu Jianhong , Gan Lei , Wu Yongyou , Zhuang Zhixiang 
Published: January 2021

BackgroundGastric cancer (GC) is one of the most common malignancies in the world, and the fourth most frequent malignancy worldwide. YTHDF2 (YTH domain family 2, YTHDF2) binds to mRNA containing m6A, thereby regulating the localization and stability of the bound mRNA. YTHDF2 was shown to be associated with some cancer patient prognosis. However, the effect of YTHDF2 on gastric cancer and the molecular mechanism of this effect have not been documented.MethodsTo conduct this research, YTHDF2 expression levels in public databases and gastric cancer patient samples were analyzed. The effects of YTHDF2 on the growth of gastric cancer cells were detectedin vivoandin vitro.RNA-seq was used to analyze the signal pathways regulated by YTHDF2, and experiments were carried out for verification.ResultsIn our study, we found that YTHDF2 has lower expression in GC tissues and GC cells, and inhibits the growth of GC cells. In addition, the analysis of clinical data found that the expression level of YTHDF2 is closely related to the stage of GC and the survival of patients with GC. RNA sequencing results showed that overexpression of YTHDF2 significantly reduced protein expression in the FOXC2 (Forkhead box protein C2, FOXC2) signaling pathway. Finally, we found that knockout of FOXC2 reversed the inhibitory effect of YTHDF2 on GC cells.ConclusionIn summary, YTHDF2 inhibits the growth of GC cells by negatively regulating FOXC2 and may serve as a prognostic marker in GC.
Distinct Cause of Death Profiles of Hospitalized Non-alcoholic Fatty Liver Disease: A 10 Years' Cross-Sectional Multicenter Study in China
Authors: Lin Yansong , Gong Xiaorong , Li Xin , Shao Congxiang , Wu Tingfeng , Li Minrui , Li Fuxi , Ma Qianqian , Ye Junzhao , Zhong Bihui 
Published: January 2021

Background: The clinical burden and natural history of non-alcoholic fatty liver disease (NAFLD) vary globally. We aimed to investigate NAFLD-related mortality profiles in hospitalized patients in southern China.Methods: A multicenter retrospective investigation with a 10-year study period (2009–2018) analyzed 10,071 deaths during hospitalization (NAFLD: 2,015; other liver diseases: 1,140; without liver diseases: 6,916) was performed using a multiple cause of death analysis. Medical histories and biochemistry and imaging findings were extracted from the electronic medical record system. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases (ICD-10) codes.Results: The distribution of death causes in patients with NAFLD has stabilized over time, with cardio- and cerebral vascular disease (CVD) ranked first (35.6%), followed by extrahepatic malignancies (22.6%), infection (11.0%), kidney disease (7.5%), liver-related diseases (5.2%), respiratory diseases (3.9%), digestive diseases (3.5%), endocrine diseases (3.5%), and other diseases (7.2%). NAFLD patients had more deaths attributable to CVD, extrahepatic malignancies, liver-related diseases (all P &lt; 0.001) and multiorgan failure than the deceased controls. The severity of steatosis was independently associated with these relationships (liver-related diseases: OR = 1.37, 95% CI: 1.20–1.59, cardio- and cerebrovascular diseases: OR = 1.23, 95% CI: 1.19–1.31, infectious diseases: OR = 1.14, 95% CI: 1.04–1.26, and renal diseases: OR = 1.21, 95% CI: 1.02–1.47, all P &lt; 0.05) after adjustment for sex, body mass index (BMI), fasting blood glucose, low-density lipoprotein cholesterol, uric acid, metabolic syndromes and fibrosis index based on the 4 factors.Conclusion : NAFLD patients had higher proportions of death due to underlying CVD and liver-related diseases than the general population in China; these proportions positively correlated with steatosis degree.
Dynamic Manugraphy as a Promising Tool to Assess the Outcome of Limited Aponeurectomy in Patients With Dupuytren's Contracture
Authors: Garkisch Angelina , Mittlmeier Thomas , Kalpen Axel , Mühldorfer-Fodor Marion , Fischer Dagmar-C. , Wichelhaus Alice 
Published: January 2021

Background: Dupuytren's contractures interfere with physiological gripping. While limited aponeurectomy is an accepted treatment modality to restore finger mobility, methods to objectify functional outcome beyond determination of the range of motion are scarce.Methods: Patients with Dupuytren's contracture being scheduled for unilateral limited aponeurectomy were invited to participate. Clinical data were gathered prospectively by chart review and interview. The DASH-score and flexion contracture for fingers were registered prior to surgery, 3 and 6 months afterwards. At the same time, dynamic manugraphy for simultaneous recording of the grip pattern and forces generated by the affected hand and anatomic areas (i.e., thumb, index finger, middle finger, ring finger, little finger and palm) were performed. All findings obtained during the follow-up period were compared to the situation at baseline. Comparison between paired samples was done using Wilcoxon rank test. All p-values are two-sided and p &lt; 0.05 was considered to be significant.Results: Out of 23 consecutively enrolled patients, 19 (15 men, 4 women) completed follow-up examinations. Manugraphy confirmed the impairment of physiological gripping with concomitant pathological load distribution at base line. Limited aponeurectomy significantly reduced flexion contractures. However, the DASH-score remained at an excellent level in one patient, indicated improvement in 11 and worsening in seven patients. Six patients had lower grip force at t6 compared to the preoperative condition, although the preoperative flexion contracture (≥110°) was considerably improved in all of them. In four of those, the DASH-score improved while it turned worse in two of them. The force of surgically treated fingers remained unchanged in three patients while it was improved and worsened in half of the remaining patients, respectively. Manugraphy revealed physiological gripping by enlargement of contact area and higher force transmission by the fingertips in 10 of 12 patients with constant or even improved DASH-score and in three of seven patients with a worsened DASH-score.Conclusions: Assessing the reduction of flexion contracture and grip force alone is not sufficient to comprehensively reflect the functional outcome of aponeurectomy for Dupuytren's disease. Visualizing physiological grip pattern provides an additional tool to objectify the success of surgical treatment.
ISEc69-Mediated Mobilization of the Colistin Resistance Gene mcr-2 in Escherichia coli
Authors: He Yu-Zhang , Long Teng-Fei , He Bing , Li Xing-Ping , Li Gong , Chen Liang , Liao Xiao-Ping , Liu Ya-Hong , Sun Jian 
Published: January 2021

ObjectivesThe emergence of mobile colistin resistance genes has compromised the efficacy of the last resort antibiotic, colistin, in clinical treatment. The mcr-2 gene was first identified in Belgium in association with the insertion sequence ISEc69. However, the molecular mechanisms of mcr-2 mobilization are not well understood.MethodsTo further explore the mobilization of mcr-2 gene via ISEc69, we constructed a conjugative plasmid that carries an intact composite transposon Tn7052. Transposition assays were performed by conjugation, the transposition sites were characterized by arbitrary primed PCR and DNA sequencing.ResultsIn this study, we experimentally demonstrated that mcr-2 could be mobilized as a composite transposon Tn7052 and its transposition generated 8-bp AT-rich duplications in the host genome.ConclusionThese results indicate that mcr-2 gene could be mobilized by ISEc69, the current investigations provide mechanistic insights in the transposition of mcr-2.
Plasma β-Amyloid Levels Associated With Structural Integrity Based on Diffusion Tensor Imaging in Subjective Cognitive Decline: The SILCODE Study
Authors: Wang Xiaoni , Zhao Mingyan , Lin Li , Han Ying 
Published: January 2021

Background: Accumulating evidence has demonstrated that plasma β-amyloid (Aβ) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer's disease (AD). Here, we investigated the microstructural changes in WM between subjects with low and high plasma Aβ levels among individuals with subjective cognitive decline (SCD).Methods: This study included 142 cognitively normal individuals with SCD who underwent a battery of neuropsychological tests, plasma Aβ measurements, and diffusion tensor imaging (DTI) based on the Sino Longitudinal Study on Cognitive Decline (SILCODE). Using tract-based spatial statistics (TBSS), we compared fractional anisotropy (FA), and mean diffusivity (MD) in WM between subjects with low (N = 71) and high (N = 71) plasma Aβ levels (cut-off: 761.45 pg/ml for Aβ40 and 10.74 pg/ml for Aβ42).Results: We observed significantly decreased FA and increased MD in the high Aβ40 group compared to the low Aβ40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p &lt; 0.05, familywise error (FWE) corrected]. Average FA values were associated with poor performance on executive and memory assessments. No significant differences were found in either MD or FA between the low and high Aβ42 groups.Conclusion: Our results suggest that a correlation exists between WM integrity and plasma Aβ40 levels in individuals with SCD.
Decompressive Hemicraniectomy Associated With Ultrasound-Guided Minimally Invasive Puncture and Drainage Has Better Feasibility Than the Traditional Hematoma Evacuation for Deteriorating Spontaneous Intracranial Hemorrhage in the Basal Ganglia Region: A Retrospective Observational Cohort Study
Authors: Cheng Yuan , Chen Jin , Zhao Guanjian , Xie Zongyi , Huang Ning , Yang Qiang , Chen Weifu , Huang Qin 
Published: January 2021

Objectives: Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with higher mortality and disability rates; however, ideal surgical management is still to be determined for critical ICH. The purpose of this study was to prove the feasibility and unique clinical value of a novel combination, decompressive hemicraniectomy associated with ultrasound-guided minimally invasive puncture and drainage (DH + MIPD), for deteriorating ICH in the basal ganglia region.Methods: According to the enrollment criteria, 168 ICH patients were analyzed retrospectively, of which 86 patients received DH + MIPD and 82 patients received DH associated with traditional hematoma evacuation as the control group. The change process of three parameters, including hematoma size, peri-hematoma edema, and intracranial pressure (ICP), in a period of time after operation, as well as the short- and long-term therapeutic effect, was compared.Results: The DH + MIPD method could effectively achieve the evacuation rate of hematoma up to 87% at 5 days post-operation and had the significant advantages of minimal injury to cerebral tissue, less degree of edema, better effect of decreasing ICP, shorter operation time, less blood loss, and lower mortality compared with the control method. The DH + MIPD group had a significantly higher survival rate within 1 year post-operation (P = 0.007) and better functional outcome at 90 and 180 days post-operation (P = 0.004). A subgroup analysis pointed out that the DH + MIPD method had a definite survival advantage for critical ICH patients older than 60 years old and with hematoma located in the left dominant hemisphere.Conclusions: Our results proved the better feasibility of DH + MIPD on hematoma evacuation and implicated its significant advantages of reducing mortality and improving functional recovery. This method provides one more choice for the individualized therapy of ICH in the basal ganglia region.
Association of the CHA2D(S2)-VASc Score and Its Components With Overt and Silent Ischemic Brain Lesions in Patients With Atrial Fibrillation
Authors: Steiner Fabienne , Meyre Pascal B. , Aeschbacher Stefanie , Coslovsky Michael , Sinnecker Tim , Blum Manuel R. , Rodondi Nicolas , Cereda Carlo W. , di Valentino Marcello , Wenger Florence , Cussigh Andrea , Krisai Philipp , Roten Laurent , Reichlin Tobias , Conen David , Osswald Stefan , Bonati Leo H. , Kühne Michael ,   The Swiss-AF Investigators
Published: January 2021

Background: Silent and overt ischemic brain lesions are common and associated with adverse outcome. Whether the CHA2DS2-VASc score and its components predict magnetic resonance imaging (MRI)-detected ischemic silent and overt brain lesions in patients with atrial fibrillation (AF) is unclear.Methods: In this cross-sectional analysis, patients with AF were enrolled in a multicenter cohort study in Switzerland. Outcomes were clinically overt, silent [in the absence of a history of stroke/transient ischemic attack (TIA)] and any MRI-detected ischemic brain lesions. Logistic regression analyses were performed to assess the relationship of the CHA2DS2-VASc score and its components with ischemic brain lesions. An adapted CHA2D-VASc score (excluding history of stroke/TIA) for the analyses of clinically overt and silent ischemic brain lesions was used.Results: Overall, 1,741 patients were included in the analysis (age 73 ± 8 years, 27.4% female). At least one ischemic brain lesion was observed in 36.8% (clinically overt: 10.5%; silent: 22.9%; transient ischemic attack: 3.4%). The CHA2D-VASc score was strongly associated with clinically overt and silent ischemic brain lesions {odds ratio (OR) [95% confidence interval (CI)] 1.32 (1.17–1.49), p &lt; 0.001 and 1.20 (1.10–1.30), p &lt; 0.001, respectively}. Age 65–74 years (OR 2.58; 95%CI 1.29–5.90; p = 0.013), age ≥75 years (4.13; 2.07–9.43; p &lt; 0.001), hypertension (1.90; 1.28–2.88; p = 0.002) and diabetes (1.48; 1.00–2.18; p = 0.047) were associated with clinically overt brain lesions, whereas age 65–74 years (1.95; 1.26–3.10; p = 0.004), age ≥75 years (3.06; 1.98–4.89; p &lt; 0.001) and vascular disease (1.39; 1.07–1.79; p = 0.012) were associated with silent ischemic brain lesions.Conclusions: A higher CHA2D-VASc score was associated with a higher risk of both overt and silent ischemic brain lesions.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02105844.
Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model
Authors: Bader Werner , Gottfried Timo , Degenhart Gerald , Johnson Chacko Lejo , Sieber Daniel , Riechelmann Herbert , Fischer Natalie , Hoermann Romed , Glueckert Rudolf , Schrott-Fischer Anneliese , Schmutzhard Joachim 
Published: January 2021

Introduction: Cochlea implants can cause severe trauma leading to intracochlear apoptosis, fibrosis, and eventually to loss of residual hearing. Mild hypothermia has been shown to reduce toxic or mechanical noxious effects, which can result in inflammation and subsequent hearing loss. This paper evaluates the usability of standard surgical otologic rinsing as cooling medium during cochlea implantation as a potential hearing preservation technique.Material and Methods: Three human temporal bones were prepared following standard mastoidectomy and posterior tympanotomy. Applying a retrocochlear approach leaving the mastoidectomy side intact, temperature probes were placed into the basal turn (n = 4), the middle turn (n = 2), the helicotrema, and the modiolus. Temperature probe positions were visualized by microcomputed tomography (μCT) imaging and manually segmented using Amira® 7.6. Through the posterior tympanotomy, the tympanic cavity was rinsed at 37°C in the control group, at room temperature (in the range between 22 and 24°C), and at iced water conditions. Temperature changes were measured in the preheated temporal bone. In each temperature model, rinsing was done for 20 min at the pre-specified temperatures measured in 0.5-s intervals. At least five repetitions were performed. Data were statistically analyzed using pairwise t-tests with Bonferroni correction.Results: Steady-state conditions achieved in all three different temperature ranges were compared in periods between 150 and 300 s. Temperature in the inner ear started dropping within the initial 150 s. Temperature probes placed at basal turn, the helicotrema, and middle turn detected statistically significant fall in temperature levels following body temperature rinses. Irrigation at iced conditions lead to the most significant temperature drops. The curves during all measurements remained stable with 37°C rinses.Conclusion: Therapeutic hypothermia is achieved with standard surgical irrigation fluid, and temperature gradients are seen along the cochlea. Rinsing of 120 s duration results in a therapeutic local hypothermia throughout the cochlea. This otoprotective procedure can be easily realized in clinical practice.
Safety and Efficacy of Magnetic Resonance-Guided Focused Ultrasound Surgery With Autofocusing Echo Imaging
Authors: Chang Kyung Won , Rachmilevitch Itay , Chang Won Seok , Jung Hyun Ho , Zadicario Eyal , Prus Oleg , Chang Jin Woo 
Published: January 2021

ObjectiveMagnetic resonance-guided focused ultrasound surgery (MRgFUS) lesioning is a new treatment for brain disorders. However, the skull is a major barrier of ultrasound sonication in MRgFUS because it has an irregular surface and varies its size and shape among individuals. We recently developed the concept of skull density ratio (SDR) to select candidates for MRgFUS from among patients with essential tremor (ET). However, SDR is not the only factor contributing to successful MRgFUS lesioning treatment—refining the target through exact measurement of the ultrasonic echo in the transducer also improves treatment efficacy. In the present study, we carried out MRgFUS lesioning using an autofocusing echo imaging technique. We aimed to evaluate the safety and efficacy of this new approach, especially in patients with low SDR in whom previous focusing methods have failed.MethodsFrom December 2019 to March 2020, we recruited 10 patients with ET or Parkinson’s disease (PD) who had a low SDR. Two patients dropped out of the trial due to the screening failure of other medical diseases. In total, eight patients were included: six with ET who underwent MRgFUS thalamotomy and two with PD who underwent MRgFUS pallidotomy. The autofocusing echo imaging technique was used in all cases.ResultsThe mean SDR of the patients with ET was 0.34 (range: 0.29–0.39), while that of the patients with PD was 0.41 (range: 0.38–0.44). The mean skull volume of patients with ET was 280.57 cm3 (range: 227–319 cm3), while that of the patients with PD was 287.13 cm3 (range: 271–303 cm3). During MRgFUS, a mean of 15 sonications were performed, among which a mean of 5.63 used the autofocusing technique. The mean maximal temperature (Tmax) achieved was 55.88°C (range: 52–59°C), while the mean energy delivered was 34.75 kJ (range: 20–42 kJ) among all patients. No serious adverse events occurred during or after treatment. Tmax or sonication factors (skull volume, SDR, sonication number, autofocusing score, similarity score, energy range, and power) were not correlated with autofocusing technique (p &gt; 0.05, autofocusing score showed a p-value of 0.071).ConclusionUsing autofocusing echo imaging lesioning, a safe and efficient MRgFUS treatment, is available even for patients with a low SDR. Therefore, the indications for MRgFUS lesioning could be expanded to include patients with ET who have an SDR &lt; 0.4 and those with PD who have an SDR &lt; 0.45.Clinical Trial Registrationclinicaltrials.gov, identifier: NCT03935581.
Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma
Authors: Cai Lei , Wang Jiangfeng , Yan Junrong , Zeng Jian , Zhu Liang , Liang Jinxiao , Pan Chao , Huang Xiancong , Jin Ju , Xu Yang , Wang Fufeng , Shao Yang , Xu Qinqin , Xia Guojie , Xing Minyan , Xu Xiaoling , Jiang Youhua 
Published: January 2021

BackgroundInvasive mucinous adenocarcinoma (IMA) of the lung is a distinct histological subtype with unique clinical and pathological features. Despite previous genomic studies on lung IMA, the genetic characteristics and the prognosis-related biomarkers in Chinese surgically resected lung IMA remain unclear.MethodsWe collected 76 surgically resected primary tumors of invasive lung adenocarcinoma, including 51 IMA and 25 non-mucinous adenocarcinomas (non-IMA). IMA was further divided into pure-IMA (mucinous features≥90%) and mixed-IMA subgroups. Comprehensive genomic profiling based on targeted next-generation sequencing (NGS) of 425 genes was explored and genomic characteristics were evaluated for the correlation with postoperative disease-free survival (DFS).ResultsIMA had a unique genetic profile, with more diverse driver mutations and more tumor drivers/suppressors co-occurrence than that of non-IMA. The frequency of EGFR (72.0% vs. 40.0% vs. 23.1%, p=0.002) and ALK (undetected vs. 20.0% vs. 26.9%, p=0.015) alterations showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. The frequency of KRAS mutations in pure-IMA was higher than that in mixed-IMA, albeit statistically insignificant (23.1% vs. 4.0%, p=0.10). TP53 mutation was significantly less in pure-IMA compared to mixed-IMA and non-IMA (23.1% vs. 52.0% vs. 56.0%, p=0.03). Besides, IMA exhibited less arm-level amplifications (p=0.04) and more arm-level deletions (p=0.004) than non-IMA, and the frequency of amplification and deletion also showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. Furthermore, prognosis analysis in stage III IMA patients showed that patients harboring alterations in EGFR (mDFS=30.3 vs. 16.0 months, HR=0.19, P=0.027) and PI3K pathway (mDFS=36.0 vs. 16.0 months, HR=0.12, P=0.023) achieved prolonged DFS, while patients with poorly differentiated tumors (mDFS=14.1 vs. 28.0 months, HR=3.75, p=0.037) or with KRAS mutations (mDFS=13.0 vs. 20.0 months, HR=6.95, p=0.027) had shorter DFS. Multivariate analysis showed that KRAS mutations, PI3K pathway alterations, and tumor differentiation status were independent factors that have statistically significant influences on clinical outcomes of IMA patients.ConclusionOur study provided genomic insights into Chinese surgically resected lung IMA. We also identified several genomic features that may serve as potential biomarkers on postoperative recurrence in IMA patients with stage III disease.