bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study
Authors: Qiao Shan , Wu Huai-kuan , Liu Ling-ling , Zhang Ran-ran , Wang Mei-ling , Han Tao , Zhang Shan-chao , Liu Xue-wu 
Published: May 2021

Objective: This study aimed to investigate epidemiological characteristics, clinical manifestations, and long-term outcomes of patients with autoimmune encephalitis (AE) in the east of China.Methods: From January 2015 to December 2019, 226 potential AE patients were recruited from five clinical centers, and a total of 185 patients who met the diagnostic criteria were included in the study. We retrospectively reviewed clinical features, auxiliary examinations, details of treatments, and outcomes of AE, and identified risk factors of poor prognosis. Modified Rankin Scale scores were used to evaluate neurological function, and scores of 3–6 indicated a poor-prognosis.Results: Patients with five main subtypes of AE were enrolled in the study, as follows: anti-NMDAR (79), anti-LGI1 (55), anti-CASPR2 (30), anti-GABABR (16), and anti-AMPAR (5). Among 185 patients, 58.38% (108/185) were male and 41.62% (77/185) were female. The median age at disease onset was 41 years (interquartile range, 17–62). The most common clinical manifestations of AE were seizures (146, 78.92%) and memory deficit (123, 66.49%). A total of 95 (51.35%) patients had abnormal brain magnetic resonance imaging results. Electroencephalographic findings were abnormal in 131 (70.81%) patients, and 168 (90.81%) and 26 (14.05%) patients were treated with first- and second-line immunotherapies, respectively. All surviving patients were followed-up for at least 1 year (range 12–36 months). Good clinical outcomes were achieved in 117 (63.24%), while 68 (36.76%) patients had a poor prognosis. Further, 33 (17.84%) patients relapsed and 10 (5.41%) died within 1 year post-discharge. Older patients tended to have a poorer prognosis, and the occurrence of mental behavioral disorders, movement disorders, disturbance of consciousness, central hypoventilation, and tumors were overrepresented in the poor-prognosis group.Conclusions: AE is a treatable disease, and most patients have a good prognosis. There are differences in the clinical manifestations of patients with different AE subtypes. Some with AE will relapse, and long-term follow-up is of great significance for further research.
The Association Between Clinical Characteristics and Motor Symptom Laterality in Patients With Parkinson's Disease
Authors: Zhu Sha , Zhong Min , Bai Yu , Wu Zhuang , Gu Ruxin , Jiang Xu , Shen Bo , Zhu Jun , Pan Yang , Dong Jingde , Xu Pingyi , Yan Jun , Zhang Li 
Published: May 2021

Background and Purpose: The unilateral onset and persistent asymmetry of motor symptoms are important characteristics of Parkinson's disease (PD). By using scales and wearable sensors, this study explored whether motor symptom laterality could affect non-motor symptom and gait performance.Methods: A total of 130 right-handed patients with PD were enrolled in our study and were divided into two groups according to the side of predominant motor symptom presentation by using the Unified Parkinson's Disease Rating Scale part III. We measured the non-motor symptoms with the Non-motor symptoms Scale, sleep quality with the Parkinson's Disease Sleep Scale and Pittsburgh sleep quality index, cognitive function with the Mini-mental State Examination and Montreal Cognitive Assessment, quality of life with the Parkinson's Disease Questionnaire-39, and the severity of anxiety and depression with the Hamilton Anxiety Scale and Hamilton Depression Scale, respectively. All participants underwent the instrumented stand and walk test, and gait data were collected using a set of JiBuEn gait analysis system.Results: We observed that left-dominant symptom PD patients (LPD) were associated with a greater impairment of sleep quality than right-dominant symptom PD patients (RPD). We found no difference between LPD and RPD in terms of gait performance. However, compared with the severe asymmetry RPD patients (RPD-S), severe asymmetry LPD patients (LPD-S) showed a shorter stride length and decreased range of motion of hip joints.Conclusions: In this study, LPD was associated with a more severe sleep-related dysfunction than RPD. In addition, LPD-S exhibited more gait impairments than RPD-S. Considering that motor symptom laterality may affect the non-motor symptom and gait performance, it should be taken into account when evaluating and treating PD patients.
CACNA1A-Linked Hemiplegic Migraine in GLUT 1 Deficiency Syndrome: A Case Report
Authors: Scoppola Chiara , Magli Giorgio , Conti Marta , Fadda Maria , Luzzu Giovanni M. , Simula Delia M. , Carta Alessandra , Sotgiu Stefano , Casellato Susanna 
Published: May 2021

Background: Glucose-transporter-1 deficiency syndrome (GLUT1-DS), due to SLC2A1 gene mutation, is characterized by early-onset seizures, which are often drug-resistant, developmental delay, and hypotonia. Hemiplegic migraine (HM) is a rare form of migraine, defined by headache associated with transient hemiplegia, and can be caused by mutations in either CACNA1A, ATP1A2, or SCN1A. Paroxysmal movements, other transient neurological disorders, or hemiplegic events can occur in GLUT1-DS patients with a mild phenotype.Case: We report on a girl with GLUT1-DS, due to SLC2A1 mutation, with a mild phenotype. In early childhood, she developed epilepsy and mild cognitive impairment, balance disorders, and clumsiness. At the age of 9, the patient reported a first hemiplegic episode, which regressed spontaneously. Over the next 3 years, two similar episodes occurred, accompanied by headache. Therefore, in the hypothesis of HM, genetic testing was performed and CACNA1A mutation was identified. The treatment with Lamotrigine avoided the recurrence of HM episodes.Discussion: To our knowledge, among the several cases of GLUT1-DS with HM symptoms described in the literature, genetic testing was only performed in two of them, which eventually proved to be negative. In all other cases, no other genes except for SLC2A1 were examined. Consequently, our patient would be the first description of GLUT1-DS with HM due to CACNA1A mutation. We would emphasize the importance of performing specific genetic testing in patients with GLUT1-DS with symptoms evocative of HM, which may allow clinicians to use specific pharmacotherapy.
Blocking Tics in Gilles de la Tourette Syndrome
Authors: Kaczyńska Justyna , Janik Piotr 
Published: May 2021

Introduction: Patients with Gilles de la Tourette syndrome (GTS) may experience blocking tics (BTs) defined as recurrent, brief cessations of motor acts. The aim of this study was to assess the prevalence, age of onset, and clinical correlates of BTs in GTS patients.Materials and Methods: We performed a one-time registration study in a cohort of 195 consecutive GTS patients aged 5–66 years (mean age: 15.0 ± 9.2; 47 females, 24.1%). All patients were personally interviewed and examined.Results: At least one BT occurred at some point in the lifetime of 73 patients (37.4%) with a mean age of onset of 10.4 ± 5.9 years. BTs occurred an average of 4.8 ± 5.3 years after tic onset. The most common BT was cessation of walking (n = 59, 80.8%), followed by speech (n = 19, 26.0%), running (n = 18, 24.7%), and writing (n = 9, 12.3%). Most of the patients (n = 52, 71.2%) reported cessation of only one activity. Clinical associations of BTs included more severe tics, overall greater number of tics, and, to a lesser extent, higher age at evaluation and comorbid obsessive-compulsive disorder.Conclusions: BTs represent complex tics, early and common symptoms of GTS, and are associated with a more severe form of GTS.
Association of Phase Angle, but Not Inflammation and Overhydration, With Physical Function in Peritoneal Dialysis Patients
Authors: Silva Vanessa Mota , Silva Maryanne Zilli Canedo , Vogt Barbara Perez , Reis Nayrana Soares Carmo , Costa Fabiana Lourenço , Dorna Mariana Souza , Minicucci Marcos Ferreira , Caramori Jacqueline Costa Teixeira 
Published: May 2021

Introduction: Muscle mass depletion, overhydration, and inflammatory state have been related to impaired physical function in chronic kidney disease patients. The relationship between bioelectrical impedance analysis (BIA) parameters, such as hydration status and phase angle (PhA), with physical function in peritoneal dialysis (PD), is still not well-established. Therefore, the objective was to evaluate the association of BIA parameters (overhydration index and PhA) and inflammatory markers with physical function in patients on PD.Methods: The present cross-sectional study enrolled PD patients. Multifrequency BIA was performed to obtain overhydration index and PhA. The Short Physical Performance Battery (SPPB) test battery was applied to assess physical function. The time to complete the 4-m gait test and sit-to-stand test was also considered for physical function assessment. The inflammatory markers tumor necrosis factor-alpha and C-reactive protein levels were determined. Multiple linear regression models were performed, with the physical function variables as dependent variables, adjusted for age, diabetes, and sex.Results: Forty-nine PD patients were enrolled, 53.1% (n = 26) women; mean age, 55.5 ± 16.3 years. There were significant correlations between PhA and SPPB (r = 0.550, p &lt; 0.001), time of 4-m gait test (r = −0.613, p &lt; 0.001) and sit-to-stand test and (r = −0.547, p &lt; 0.001). Overhydration index was significantly correlated with SPPB, 4-m gait test (r = 0.339, p = 0.017), and sit-to-stand test (r = 0.335, p = 0.019). Inflammatory markers were not significantly correlated with physical function parameters. In the multiple linear regression analysis, PhA was associated with physical function parameters, even after adjustments. Overhydration index was associated with all physical function tests only in the models with no adjustments.Conclusion: PhA was independently associated with physical function in PD patients. Inflammatory markers and overhydration index were not associated with physical function.
Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-Stage Lung Cancer Diagnosis
Authors: Wan Lingling , Liu Qingyi , Liang Di , Guo Yongdong , Liu Guangjie , Ren Jinxia , He Yutong , Shan Baoen 
Published: May 2021

BackgroundLung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis.MethodsIn this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients. To screen potential diagnostic markers for early lung cancer.Results62.5% (30/48) of lung cancer patients had ≥1 CTC. By CTC NGS, we found that &gt; 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC &gt;0.9).ConclusionsOur results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer.
A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
Authors: Huang Shenq-Shyang , Liao Wen-Ying , Hsu Chung-Chi , Chan Tze-Sian , Liao Tai-Yan , Yang Pei-Ming , Chen Li-Tzong , Sung Shian-Ying , Tsai Kelvin K. 
Published: May 2021

IntroductionStem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation.MethodsThe cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies.ResultsWe showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1+ CSCs have stronger mesenchymal properties than their sENO1- counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1+ CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness.ConclusionsOur study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers.
Prevalence of TP-53/Rb-1 Co-Mutation in Large Cell Neuroendocrine Carcinoma
Authors: Saghaeiannejad Esfahani Hoda , Vela Cory M. , Chauhan Aman 
Published: May 2021

IntroductionLarge cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive high-grade neuroendocrine neoplasm, which can arise from anywhere in the body. Due to its rarity there is a lacuna in our understanding of LCNEC’s molecular biology. In 2016, Rekhtman and colleagues presented one of the largest molecular sequencing series of pulmonary LCNEC. They differentiated genomic profiles of LCNEC into two major subsets: small cell lung cancer (SCLC)-like, characterized by TP53 + RB1 co-mutation/loss, and non-small cell lung cancer (NSCLC)-like, characterized by the lack of co-altered TP53 + RB1. This finding is of significance because at present LCNEC patients are often treated like SCLC. However, the universal genomic SCLC biomarker of TP53 and RB1 co-mutation was only found in 40% of their cohort. Since then various other scientists have looked into molecular profiling of LCNEC with markedly discordant results. The objective of this study was to conduct a systematic review of publicly available next generation sequencing (NGS) data to evaluate the prevalence of TP53 + RB1 co-mutation in LCNEC.MethodWe conducted a literature search using PubMed. Seven studies including 302 patients with pulmonary LCNEC and four studies including 20 patients with extra-pulmonary LCNEC underwent final analysis.ResultsThe prevalence of TP53 + RB1 co-mutation was 36% (109/302) among pulmonary LCNEC patients and 35% (7/20) among the extra-thoracic LCNEC cohort. This finding is in stark contrast to &gt;90% TP53 + RB1 co-mutation in SCLC.ConclusionIt is now well established that LCNEC is molecularly distinct from SCLC. LCNEC seems to have two molecularly defined sub-cohort based on TP53 + RB1 co-mutation status. Future studies should look into prognostic and predictive implication of TP53 + RB1 co-mutation status in LCNEC. Prospective studies should be designed to characterize molecular subtypes and direct treatment accordingly. We are currently conducting a prospective pilot clinical trial wherein LCNEC patients are treated based on TP53 + RB1 co-mutation status. The study is currently enrolling. “Next Generation Sequencing-Based Stratification of Front Line Treatment of Neuroendocrine Carcinoma (PRECISION-NEC).Systematic ReviewClinicalTrials.gov, identifier NCT04452292.
Preoperative Predictors of Lymph Node Metastasis in Colon Cancer
Authors: Xu Yansong , Chen Yi , Long Chenyan , Zhong Huage , Liang Fangfang , Huang Ling-xu , Wei Chuanyi , Lu Shaolong , Tang Weizhong 
Published: May 2021

BackgroundLymph node metastasis (LNM) is a well-established prognostic factor for colon cancer. Preoperative LNM evaluation is relevant for planning colon cancer treatment. The aim of this study was to construct and evaluate a nomogram for predicting LNM in primary colon cancer according to pathological features.Patients and MethodsSix-hundred patients with clinicopathologically confirmed colon cancer (481 cases in the training set and 119 cases in the validation set) were enrolled in the Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to December 2019. The expression of molecular markers (p53 and β-catenin) was determined by immunohistochemistry. Multivariate logistic regression was used to screen out independent risk factors, and a nomogram was established. The accuracy and discriminability of the nomogram were evaluated by consistency index and calibration curve.ResultsUnivariate logistic analysis revealed that LNM in colon cancer is significantly correlated (P &lt;0.05) with tumor size, grading, stage, preoperative carcinoembryonic antigen (CEA) level, and peripheral nerve infiltration (PNI). Multivariate logistic regression analysis confirmed that CEA, grading, and PNI were independent prognostic factors of LNM (P &lt;0.05). The nomogram for predicting LNM risk showed acceptable consistency and calibration capability in the training and validation sets.ConclusionsPreoperative CEA level, grading, and PNI were independent risk factor for LNM. Based on the present parameters, the constructed prediction model of LNM has potential application value.
N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver Tumorigenesis via Differentially Regulating Ubiquitination of Targets
Authors: Zhu Guoqing , Wang Feng , Li Haojie , Zhang Xiao , Wu Qi , Liu Ya , Qian Mingping , Guo Susu , Yang Yueyue , Xue Xiangfei , Sun Fenyong , Qiao Yongxia , Pan Qiuhui 
Published: May 2021

BackgroundA tremendous amount of studies have suggested that post-translational modifications (PTMs) play pivotal roles during tumorigenesis. Compared to other PTMs, lipid modification is less studied. Recently, N-myristoylation, one type of lipid modification, has been paid attention to the field of cancer. However, whether and how N-myristoylation exerts its roles in liver tumorigenesis still remains unclear.MethodsParallel reaction monitoring (PRM) was conducted to evaluate the expression of protein modification enzymes in paired tissues. Liver conditionally knocking NMT1 out mice model was used to assess the critical roles of N-myristoylation during liver tumorigenesis. Proteomics isobaric tags for relative and absolute quantification (iTraq) was performed to identify proteins that changed while NMT1 was knocked down. The click chemistry assay was used to evaluate the N-myristoylation levels of proteins.ResultsHere, N-myristolyation and its enzyme NMT1, but not NMT2, were found to be critical in liver cancer. Two categories of proteins, i.e., N-myristolyation down-regulated proteins (NDP, including LXN, RPL29, and FAU) and N-myristolyation up-regulated proteins (NUP, including AHSG, ALB, and TF), were revealed negatively and positively regulated by NMT1, respectively. Both NDP and NUP could be N-myristolyated by NMT1 indispensable of POTEE. However, N-myristolyation decreased and increased stability of NDP and NUP, respectively. Mechanistically, NDP-specific binding protein RPL7A facilitated HIST1H4H, which has ubiquitin E3 ligase function, to ubiquitinate NDP. By contrast, NUP-specific binding protein HBB prevented NUP from ubiquitination by HIST1H4H. Notably, function of RPL7A and HBB was all NMT1-dependent. Moreover, NDP suppressed while NUP stimulated transformative phenotypes. Clinically, higher levels of NMT1 and NUP with lower levels of NDP had worse prognostic outcome.ConclusionCollectively, N-myristolyation by NMT1 suppresses anti-tumorigenic NDP, whereas it stimulates pro-tumorigenic NUP by interfering their ubiquitination to finally result in a pro-tumorigenic outcome in liver cancer. Targeting N-myristolyation and NMT1 might be helpful to treat liver cancer.
Development and Validation of a Nomogram Based on Nutritional Indicators and Tumor Markers for Prognosis Prediction of Pancreatic Ductal Adenocarcinoma
Authors: Li Haoran , Zhou Fang , Cao Zhifei , Tang Yuchen , Huang Yujie , Li Ye , Yi Bin , Yang Jian , Du Peng , Zhu Dongming , Zhou Jian 
Published: May 2021

PurposeThis study aimed to develop and validate a nomogram with preoperative nutritional indicators and tumor markers for predicting prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).MethodsWe performed a bicentric, retrospective study including 155 eligible patients with PDAC. Patients were divided into a training group (n = 95), an internal validation group (n = 34), an external validation group (n = 26), and an entire validation group (n = 60). Cox regression analysis was conducted in the training group to identify independent prognostic factors to construct a nomogram for overall survival (OS) prediction. The performance of the nomogram was assessed in validation groups and through comparison with controlling nutritional status (CONUT) and prognostic nutrition index (PNI).ResultsThe least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate Cox regression analysis revealed that serum albumin and lymphocyte count were independent protective factors while CA19-9 and diabetes were independent risk factors. The concordance index (C-index) of the nomogram in the training, internal validation, external validation and entire validation groups were 0.777, 0.769, 0.759 and 0.774 respectively. The areas under curve (AUC) of the nomogram in each group were 0.861, 0.845, 0.773, and 0.814. C-index and AUC of the nomogram were better than those of CONUT and PNI in the training and validation groups. The net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis showed improvement of accuracy of the nomogram in predicting OS and better net benefit in guiding clinical decisions in comparison with CONUT and PNI.ConclusionsThe nomogram incorporating four preoperative nutritional and tumor markers including serum albumin concentration, lymphocyte count, CA19-9 and diabetes mellitus could predict the prognosis more accurately than CONUT and PNI and may serve as a clinical decision support tool to determine what treatment options to choose.