bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bubble Test and Carotid Ultrasound to Guide Indication of Transesophageal Echocardiography in Young Patients With Stroke
Authors: Mayerhofer Ernst , Kanz Dirk , Guschlbauer Brigitte , Anderson Christopher D. , Asmussen Alexander , Grundmann Sebastian , Strecker Christoph , Harloff Andreas 
Published: March 2022

Background and PurposeIndication of transesophageal echocardiography (TEE) in patients ≤60 years with brain ischemia is uncertain.MethodsThis prospective double-blinded study included patients with cryptogenic acute ischemic stroke or transient ischemic attack (TIA) ≥18 and ≤60 years. After routine diagnostics, all patients underwent patent foramen ovale (PFO) screening by transcranial Doppler (TCD) bubble test, carotid ultrasound for atherosclerosis screening (intima-media-thickness &gt;0.90 mm or plaques), and TEE. We calculated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the combined non-invasive ultrasound to predict therapy-relevant TEE findings.ResultsWe included 240 consecutive patients (median 51 years, 39% women) of which 68 (28.3%) had both a negative bubble test and no carotid atherosclerosis. Of these, 66 (97.1%) had unremarkable TEE findings; in one patient a small PFO was found and closed subsequently, in another patient a 4.9 mm thick aortic atheroma was found, and double platelet inhibition initiated. Of the other 172 (71.7%) patients, 93 (54%) had PFO and 9 (5.2%) complex aortic plaques. No other therapy-relevant findings were present in both groups. Non-invasive ultrasound had a sensitivity of 98.0%, specificity of 47.8%, NPV of 97.1%, and PPV of 58.1% for therapy-relevant TEE findings.ConclusionsBubble test and carotid ultrasound could be used for the individual decision for/against TEE in patients with cryptogenic stroke ≤60 years. If they are unremarkable, TEE can be omitted with high safety regarding secondary prevention. If bubble test is positive and/or carotid ultrasound shows atherosclerosis, TEE should be carried out if PFO or aortic atheroma are potentially relevant for further patient management.
Design and Evaluation of a Custom-Made Electromyographic Biofeedback System for Facial Rehabilitation
Authors: Machetanz Kathrin , Grimm Florian , Schäfer Ruth , Trakolis Leonidas , Hurth Helene , Haas Patrick , Gharabaghi Alireza , Tatagiba Marcos , Naros Georgios 
Published: March 2022

BackgroundIn the rehabilitation of postoperative facial palsy, physical therapy is of paramount importance. However, in the early rehabilitation phase, voluntary movements are often limited, and thus, the motivation of patients is impacted. In these situations, biofeedback of facial electromyographic (EMG) signals enables the visual representation of the rehabilitation progress, even without apparent facial movements. In the present study, we designed and evaluated a custom-made EMG biofeedback system enabling cost-effective facial rehabilitation.MethodsThis prospective study describes a custom-made EMG system, consisting of a microcontroller board and muscle sensors, which was used to record the EMG of frontal and zygomatic facial muscles during frowning and smiling. First, the mean EMG amplitudes and movement onset detection rates (ACC) achieved with the custom-made EMG system were compared with a commercial EMG device in 12 healthy subjects. Subsequently, the custom-made device was applied to 12 patients with and without postoperative facial paresis after neurosurgical intervention. Here, the ratio [laterality index (LI)] between the mean EMG amplitude of the healthy and affected side was calculated and related to the facial function as measured by the House and Brackmann scale (H&amp;B) ranging from 1 (normal) to 6 (total paralysis).ResultsIn healthy subjects, a good correlation was measured between the mean EMG amplitudes of the custom-made and commercial EMG device for both frontal (r = 0.84, p = 0.001) and zygomatic muscles (r = 0.8, p = 0.002). In patients, the LI of the frontal and zygomatic muscles correlated significantly with the H&amp;B (r = −0.83, p = 0.001 and r = −0.65, p = 0.023). The ACC of the custom-made EMG system varied between 65 and 79% depending on the recorded muscle and cohort.ConclusionThe present study demonstrates a good application potential of our custom-made EMG biofeedback device to detect facial EMG activity in healthy subjects as well as patients with facial palsies. There is a correlation between the electrophysiological measurements and the clinical outcome. Such a device might enable cost-efficient home-based facial EMG biofeedback. However, movement detection accuracy should be improved in future studies to reach ranges of commercial devices.
Chronic Lactate Exposure Decreases Mitochondrial Function by Inhibition of Fatty Acid Uptake and Cardiolipin Alterations in Neonatal Rat Cardiomyocytes
Authors: San-Millan Iñigo , Sparagna Genevieve C. , Chapman Hailey L. , Warkins Valerie L. , Chatfield Kathryn C. , Shuff Sydney R. , Martinez Janel L. , Brooks George A. 
Published: March 2022

IntroductionLactate is an important signaling molecule with autocrine, paracrine and endocrine properties involved in multiple biological processes including regulation of gene expression and metabolism. Levels of lactate are increased chronically in diseases associated with cardiometabolic disease such as heart failure, type 2 diabetes, and cancer. Using neonatal ventricular myocytes, we tested the hypothesis that chronic lactate exposure could decrease the activity of cardiac mitochondria that could lead to metabolic inflexibility in the heart and other tissues.MethodsNeonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 5, 10, or 20 mM lactate and CPT I and II activities were tested using radiolabelled assays. The molecular species profile of the major mitochondrial phospholipid, cardiolipin, was determined using electrospray ionization mass spectrometry along with reactive oxygen species (ROS) levels measured by Amplex Red and mitochondrial oxygen consumption using the Seahorse analyzer.ResultsCPT I activity trended downward (p = 0.07) and CPT II activity significantly decreased with lactate exposure (p &lt; 0.001). Cardiolipin molecular species containing four 18 carbon chains (72 carbons total) increased with lactate exposure, but species of other sizes decreased significantly. Furthermore, ROS production was strongly enhanced with lactate (p &lt; 0.001) and mitochondrial ATP production and maximal respiration were both significantly down regulated with lactate exposure (p &lt; 0.05 and p &lt; 0.01 respectively).ConclusionsChronic lactate exposure in cardiomyocytes leads to a decrease in fatty acid transport, alterations of cardiolipin remodeling, increases in ROS production and decreases in mitochondrial oxygen consumption that could have implications for both metabolic health and flexibility. The possibility that both intra-, or extracellular lactate levels play roles in cardiometabolic disease, heart failure, and other forms of metabolic inflexibility needs to be assessed in vivo.
Comprehensive Analysis Identified Mutation-Gene Signature Impacts the Prognosis Through Immune Function in Hepatocellular Carcinoma
Authors: Lin Zhuo , Xu Qian , Song Xian , Zeng Yuan , Zeng Liuwei , Zhao Luying , Xu Jun , Miao Dan , Chen Zhuoyan , Yu Fujun 
Published: March 2022

BackgroundHepatocellular carcinoma (HCC) is a life-threatening and refractory malignancy with poor outcome. Genetic mutations are the hallmark of cancer. Thus far, there is no comprehensive prognostic model constructed by mutation-gene transcriptome in HCC. The prognostic value of mutation-gene signature in HCC remains elusive.MethodsRNA expression profiles and the corresponding clinical information were recruited from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was employed to establish gene signature. Kaplan–Meier curve and time-dependent receiver operating characteristic curve were implemented to evaluate the prognostic value. The Wilcoxon test was performed to analyze the expression of immune checkpoint genes, cell cycle genes, and tumor drug resistance genes in different risk groups. Finally, quantitative real-time PCR (qRT-RCR) and immunohistochemistry (IHC) were performed to validate the mRNA and protein expression between HCC and adjacent nontumorous tissues in an independent cohort.ResultsA prognostic model consisting of five mutated genes was established by LASSO Cox regression analysis. The prognostic model classified patients into high- and low-risk groups. Compared with the low‐risk group, patients in the high‐risk group had significantly worse survival results. The prognostic model can accurately predict the overall survival of HCC patients and predict overall survival more accurately when combined with stage. Furthermore, the immune checkpoint genes, cell cycle genes, and tumor drug resistance genes were higher expressed in the high-risk group compared in the low-risk group. In addition, the expression level of prognostic signature genes was validated in an independent sample cohort, which was consistent with RNA sequencing expression in the TCGA database.ConclusionThe prediction model of HCC constructed using mutation-related genes is of great significance for clinical decision making and the personalized treatment of patients with HCC.
Association of HER-2/CEP17 Ratio and HER-2 Copy Number With pCR Rate in HER-2-Positive Breast Cancer After Dual-Target Neoadjuvant Therapy With Trastuzumab and Pertuzumab
Authors: Li Fanfan , Ju Qian , Gao Cong , Li Jingjing , Wang Xiaolei , Yan Min , Zhang Liying , Huang Meiling , Long Qihe , Jin Xiangting , Li Nanlin 
Published: March 2022

ObjectiveTo explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab.MethodsA total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value.ResultsIHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p&lt;0.001) and the ratio of HER-2/cell number (p&lt;0.001) was significantly correlated with the pCR rate. ROC analysis showed that patients with an HER-2/CEP17 ratio ≥4.495 or HER-2/cell number ≥11.650 have a high pCR rate after dual anti-HER-2 neoadjuvant therapy, suggesting its predictive significance.ConclusionThe response to dual-targeted neoadjuvant therapy with trastuzumab and pertuzumab was adequate in hormone receptor-negative, HER-2-positive breast cancer patients. HER-2/CEP17 ratio and HER-2/cell number ratio were crucial for predicting efficacy.
Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis
Authors: Zhang Yu-fei , Fan Yu , Zhang Peng , Ruan Jia-ying , Mu Yi , Li Jin-ke 
Published: March 2022

ObjectiveTo compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT).MethodsWe systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.ResultsThe meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92).ConclusionsAC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).
Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis
Authors: Sun Chenyu , Ma Shaodi , Chen Yue , Kim Na Hyun , Kailas Sujatha , Wang Yichen , Gu Wenchao , Chen Yisheng , Tuason John Pocholo W. , Bhan Chandur , Manem Nikitha , Huang Yuting , Cheng Ce , Zhou Zhen , Zhou Qin , Zhu Yanzhe 
Published: March 2022

BackgroundLiver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis.ResultsThe expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC.ConclusionsFor LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.
A Promising Preoperative Prediction Model for Microvascular Invasion in Hepatocellular Carcinoma Based on an Extreme Gradient Boosting Algorithm
Authors: Liu Weiwei , Zhang Lifan , Xin Zhaodan , Zhang Haili , You Liting , Bai Ling , Zhou Juan , Ying Binwu 
Published: March 2022

BackgroundThe non-invasive preoperative diagnosis of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is vital for precise surgical decision-making and patient prognosis. Herein, we aimed to develop an MVI prediction model with valid performance and clinical interpretability.MethodsA total of 2160 patients with HCC without macroscopic invasion who underwent hepatectomy for the first time in West China Hospital from January 2015 to June 2019 were retrospectively included, and randomly divided into training and a validation cohort at a ratio of 8:2. Preoperative demographic features, imaging characteristics, and laboratory indexes of the patients were collected. Five machine learning algorithms were used: logistic regression, random forest, support vector machine, extreme gradient boosting (XGBoost), and multilayer perception. Performance was evaluated using the area under the receiver operating characteristic curve (AUC). We also determined the Shapley Additive exPlanation value to explain the influence of each feature on the MVI prediction model.ResultsThe top six important preoperative factors associated with MVI were the maximum image diameter, protein induced by vitamin K absence or antagonist-II, α-fetoprotein level, satellite nodules, alanine aminotransferase (AST)/aspartate aminotransferase (ALT) ratio, and AST level, according to the XGBoost model. The XGBoost model for preoperative prediction of MVI exhibited a better AUC (0.8, 95% confidence interval: 0.74–0.83) than the other prediction models. Furthermore, to facilitate use of the model in clinical settings, we developed a user-friendly online calculator for MVI risk prediction based on the XGBoost model.ConclusionsThe XGBoost model achieved outstanding performance for non-invasive preoperative prediction of MVI based on big data. Moreover, the MVI risk calculator would assist clinicians in conveniently determining the optimal therapeutic remedy and ameliorating the prognosis of patients with HCC.
Surfactant Therapy for Respiratory Distress Syndrome in High- and Ultra-High-Altitude Settings
Authors: Duan Xudong , Li Jiujun , Chen Long , Shi Yuan , Chen Xianyang , Xue Teng , Liu Chongde , Wang Xiaorong , Qiu Quanfang , Yu Zhen , Qiang Bacuozhen , Wu Hong , Wu Tianqi , Zhang Lihong , Chen Zhangsheng , Jigme Dobje , Xu Aili , Mima Zhuoga , Da Zhen , Ren Min , Gesang Deji , Pubu Zhaxi , Li Chun , Lv Yanchao , Zhou Haoquan , Zhang Xue , Dawa Zhuoma , Gongjue Wujin , Wang Li , Wu Li , Li Xuelian 
Published: March 2022

ObjectiveThe objective of this study is to investigate the therapeutic effect of surfactant replacement therapy (SRT) on respiratory distress syndrome (RDS) in premature infants in the Qinghai-Tibet Plateau.Materials and MethodsThis multi-center retrospective cohort study collected and screened reasonable clinical data of 337 premature infants with RDS from 10 hospitals in the Qinghai-Tibet Plateau from 2015 to 2017. We grouped the cases by rationally analyzing their baseline characteristics, using logistic analysis to evaluate each factor's effect on the prognosis of the infants, and comparing the short-term improvement in blood gas and mortality after SRT treatment at different altitudes, in high-altitude (1,500–3,500 m) and ultra-high-altitude (3,500–5,500 m) groups.ResultsIndependent of altitude, the mortality rate of children with RDS in the SRT group was significantly lower than that of children in the non-SRT group (both P &lt; 0.05). The effect of SRT on preterm infants with RDS in the high-altitude group [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.22–0.87, P = 0.02] was better than that in the infants in the ultra-high-altitude group (OR = 0.26, 95% CI = 0.13–0.58, P &lt; 0.01), with death rates of 34.34 and 49.71%, respectively. Similarly, after SRT, the improvement of PaO2/FiO2 and pH of children at high altitude was significantly better than those of children at ultra-high altitude (all P &lt; 0.01).ConclusionsSRT plays a prominent role in curing infants with RDS in both high- and ultra-high-altitude regions, although with better effects at high rather than ultra-high altitude. This study provides a basis for further large-scale studies on SRT for RDS treatment at high altitudes.
FGF4, A New Potential Regulator in Gestational Diabetes Mellitus
Authors: Fan Miaojuan , Pan Tongtong , Jin Wei , Sun Jian , Zhang Shujun , Du Yali , Chen Xinwei , Chen Qiong , Xu Wenxin , Choo Siew Woh , Zhu Guanghui , Chen Yongping , Zhou Jie 
Published: March 2022

Background: Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM.Methods: We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus.Results: We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation.Conclusions/interpretation: Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.
Controlling Nutritional Status (CONUT) Predicts Survival in Gastric Cancer Patients With Immune Checkpoint Inhibitor (PD-1/PD-L1) Outcomes
Authors: Chen Li , Sun Hao , Zhao Ruihu , Huang Rong , Pan Hongming , Zuo Yanjiao , Zhang Lele , Xue Yingwei , Song Hongjiang , Li Xingrui 
Published: March 2022

Objective: The controlling nutritional status (CONUT), based on total lymphocyte count (TL), total cholesterol level (T-CHOL), and serum albumin (ALB), can provide a useful immunological prognostic biomarker for cancer patients. The present study aims to investigate the correlation between CONUT and prognosis in gastric cancer patients receiving immune checkpoint inhibitor (ICI) treatment.Methods: We retrospectively enrolled 146 patients with gastric cancer treated with ICIs (PD-1/PD-L1 inhibitors) from August 2016 to December 2020. The clinicopathologic characteristics were analyzed by Chi-square test or Fisher’s exact test. The Kaplan–Meier and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The prognostic and predictive factors of PFS and OS were identified by univariate and multivariate analyses. A nomogram was developed to estimate 1-, 3-, and 5-year PFS and OS probability.Results: Through the CONUT score, there were 75 (51.37%) patients in the low CONUT group and 71 (48.63%) patients in the high CONUT group. There was a correlation between the CONUT score and age (p = 0.005), pathology (p = 0.043), ALB (p = 0.020), PALB (p = 0.032), and Hb (p = 0.001). The CA724, TNM stage, and treatment (ICIs vs. chemotherapy) were the independent prognostic factors for PFS and OS by multivariate analyses. Patients with high CONUT score had poorer PFS and OS (χ2 = 3.238, p = 0.072, and χ2 = 4.298, p = 0.038). In the subgroup analysis, the patients with high CONUT score were associated with shorter PFS and OS with ICIs or chemotherapy. With the PD-1/PD-L1 positive expression, the patients with high CONUT score had shorter PFS and OS than those with low CONUT score. Furthermore, the patients with high CA724 value were associated with shorter PFS and OS. The toxicity assessment in ICIs or chemotherapy was significantly associated with anemia. The nomograms were constructed to predict the probability of 1-, 3-, and 5-year PFS, and 1-, 3-, and 5-year OS with C-indices of 0.749 and 0.769, respectively.Conclusion: The CONUT, as a novel immuno-nutritional biomarker, may be useful in identifying gastric cancer patients who are unlikely to benefit from ICI treatment.