bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Novel Biomarkers for Diagnosing and Predicting the Progression of Multiple Sclerosis Using TMT-Based Quantitative Proteomics
Authors: Shi Yijun , Ding Yaowei , Li Guoge , Wang Lijuan , Osman Rasha Alsamani , Sun Jialu , Qian Lingye , Zheng Guanghui , Zhang Guojun 
Published: August 2021

ObjectiveHere, we aimed to identify protein biomarkers that could rapidly and accurately diagnose multiple sclerosis (MS) using a highly sensitive proteomic immunoassay.MethodsTandem mass tag (TMT) quantitative proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples collected from 10 patients with MS and 10 non-inflammatory neurological controls (NINCs). The DEPs were analyzed using bioinformatics tools, and the candidate proteins were validated using the ELISA method in another cohort comprising 160 samples (paired CSF and plasma of 40 patients with MS, CSF of 40 NINCs, and plasma of 40 healthy individuals). Receiver operating characteristic (ROC) curves were used to determine the diagnostic potential of this method.ResultsCompared to NINCs, we identified 83 CSF-specific DEPs out of a total of 343 proteins in MS patients. Gene ontology (GO) enrichment analysis revealed that these DEPs are mainly involved in platelet degranulation, negative regulation of proteolysis, and post-translational protein modification. Pathway enrichment analysis revealed that the complement and coagulation cascades, Ras signaling pathway, and PI3K-Akt signaling pathway are the main components. Insulin-like growth factor-binding protein 7 (IGFBP7), insulin-like growth factor 2 (IGF2), and somatostatin (SST) were identified as the potential proteins with high scores, degree, and centrality in the protein-protein interaction (PPI) network. We validated the expression of these three proteins using ELISA. Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group.ConclusionOur results suggest that SST and IGFBP7 might be associated with the pathogenesis of MS and would be helpful in diagnosing MS. Since IGFBP7 was used to classify relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients, therefore, it may act as a potential key marker and therapeutic target in MS.
Hierarchical Structure Fabrication of IPMC Strain Sensor With High Sensitivity
Authors: Chang Longfei , Wang Dongping , Hu Jiajia , Li Yan , Wang Yanjie , Hu Ying 
Published: August 2021

In this paper, a biological template method is introduced and investigated to fabricate ionic polymer-metal composite (IPMC) strain sensor with bionic hierarchical structures. We utilized the multi-level structure of reed leaf surface, which can improve the contact area between the substrate and the electrode layers. Hierarchical structures were observed on the IPMC samples, including pyramid strips with the width in the range of 60–80 μm as well as synaptic scatters with diameter around 10 μm. In addition, five kinds of sensors with different interface structures were obtained by combining the traditional microneedle roller roughening and chemical plating processes. It was found that the IPMC sensor with reed-leaf and microneedle structure on each side presented the best performance, along with a high linearity, a sensitivity of 62.5 mV/1% and a large generated voltage peak under given mechanical stimuli, which is 3.7 times that of the sample fabricated without roughening.
The Association in Myopic Tractional Maculopathy With Myopic Atrophy Maculopathy
Authors: Tian Jiaxin , Qi Yue , Lin Caixia , Cao Kai , Wang Ningli 
Published: August 2021

Purpose: To investigate the relationship between myopic tractional maculopathy (MTM) and myopic atrophy maculopathy (MAM).Method: Two hundred and six eyes with definitive myopic retinoschisis were assessed in the retrospective observational case series study and the atrophic and tractional features were further evaluated. Atrophic changes were analyzed according to the atrophic component in the ATN classification and the occurrence of gamma zones and delta zones. Tractional changes were evaluated based on different retinoschisis layers, the location and range of outer retinoschisis, retinal detachment, inner lamellar macular hole (ILMH), outer lamellar MH (OLMH), full-thickness MH (FTMH), and paravascular abnormalities.Results: Of all the eyes, 29.6, 42.7, 19.4, and 8.3% presented MAM grades with A1, A2, A3, and A4, respectively. The three layers of retinoschisis and the entire macular retinoschisis had the highest incidences in A2 (38.6%; 54.5%). The numbers of retinoschisis layers and the grades of outer retinoschisis had a weak negative correlation with MAM (r = −0.138, P = 0.048; r = −0.139, P = 0.047). All the eyes had gamma zones, and 82.52% of eyes also had delta zones. The incidence of retinal detachment and OLMH reached the peak in A2 and then decreased gradually. With MAM aggravation, the prevalence of ILMH decreased. Eyes with A1 and A2 were more likely to have OLMH, and those with A3 and A4 were more likely to have FTMH (P = 0.028; OR, 3.423; 95% CI, 1.144–10.236; P = 0.004; OR, 7.752; 95% CI, 1.951–30.803). With the MAM grades growing, the types of paravascular abnormalities increased (r = 0.165, P = 0.018).Conclusion: Diffuse chorioretinal atrophy was the dominant MAM grade in eyes with MTM. In the study, 72.3% of eyes with MTM presented with diffuse chorioretinal atrophy and a tessellated fundus. Over 80% of eyes with MTM had both gamma zones and delta zones. Diffuse chorioretinal atrophy might be a complicated stage for MTM with the highest rate of three layers of retinoschisis, the entire macular retinoschisis, RD, and OLMH. Atrophic progression might involve the development of MH. When MTM combines with well-defined atrophy, the occurrence of FTMH should be noted.
Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era
Authors: Campbell Cori , Andersson Monique I. , Ansari M. Azim , Moswela Olivia , Misbah Siraj A. , Klenerman Paul , Matthews Philippa C. 
Published: August 2021

Objectives:Tocilizumab (TCZ), an IL-6 receptor antagonist, is used in the treatment of severe COVID-19 caused by infection with SARS-CoV-2. However, unintended consequences of TCZ therapy include reactivation of tuberculosis (TB) or hepatitis B virus (HBV), and worsening of hepatitis C virus (HCV). We set out to assimilate existing data for these complications, in order to help inform evidence-based risk assessments for the use of TCZ, and thus to reduce the risk of serious but preventable complications.Methods:We searched the global WHO database of Individual Case Safety Reports (ICSRs) and adverse drug reactions (ADRs) (“VigiBase”) and undertook a systematic literature review, in accordance with PRISMA guidelines. We generated mean cumulative incidence estimates for infection complications.Results:Mean cumulative incidence of HBV and TB were 3.3 and 4.3%, respectively, in patients receiving TCZ. Insufficient data were available to generate estimates for HCV. These estimates derive from heterogeneous studies pre-dating SARS-CoV-2, with differing epidemiology and varied approaches to screening and prophylaxis, so formal meta-analysis was not possible.Conclusions:We underline the need for careful individual risk assessment prior to TCZ prescription, and present an algorithm to guide clinical stratification. There is an urgent need for ongoing collation of safety data as TCZ therapy is used in COVID.
Abnormal Neural Activity in Different Frequency Bands in Parkinson’s Disease With Mild Cognitive Impairment
Authors: Rong Siming , Zhang Piao , He Chentao , Li Yan , Li Xiaohong , Li Ruitao , Nie Kun , Huang Sifei , Wang Limin , Wang Lijuan , Zhang Yuhu 
Published: August 2021

Background: Abnormal spontaneous neural activity is often found in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps.Methods: Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups.Results: In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III).Conclusion: Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI.
Effect of Body Mass Index on the Prognosis of Liver Cirrhosis
Authors: Yin Yue , Li Yiling , Shao Lichun , Yuan Shanshan , Liu Bang , Lin Su , Yang Yida , Tang Shanhong , Meng Fanping , Wu Yunhai , Chen Yu , Li Bimin , Zhu Qiang , Qi Xingshun 
Published: August 2021

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI &lt;18.5 kg/m2), normal weight (18.5 ≤ BMI &lt; 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2).Results: In the first part, Kaplan–Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405–0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child–Pugh score (HR = 0.758; 95%CI: 0.479–1.199; p = 0.236). In the second part, Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups.Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.
Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers
Authors: Hamdi Yosr , Mighri Najah , Boujemaa Maroua , Mejri Nesrine , Ben Nasr Sonia , Ben Rekaya Mariem , Messaoud Olfa , Bouaziz Hanen , Berrazega Yosra , Rachdi Haifa , Jaidane Olfa , Daoud Nouha , Zribi Aref , Ayari Jihene , El Benna Houda , Labidi Soumaya , Ben Hassouna Jamel , Haddaoui Abderazzek , Rahal Khaled , Benna Farouk , Mrad Ridha , Ben Ahmed Slim , Boussen Hamouda , Boubaker Samir , Abdelhak Sonia 
Published: August 2021

BackgroundBreast cancer is the world’s most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations.MethodsA total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated.ResultsIn the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T&gt;A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations.ConclusionOur study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.
Prognostic Role of Programmed Death Ligand-1 on Tumor-Infiltrating Immune Cells in “High-Risk” Patients Following Radical Cystectomy: A Retrospective Cohort Study
Authors: Lee Chung Un , Lee Dong Hyeon , Song Wan 
Published: August 2021

PurposeThe aim of this study is to investigate the prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TIICs) in patients after radical cystectomy (RC) for bladder cancer (BCa).Materials and MethodsWe retrospectively reviewed 92 “high-risk” (≥pT3a and/or pN+) patients who underwent RC for BCa, without adjuvant chemotherapy (AC), between April 2014 and December 2019. PD-L1 on TIICs was measured only using the VENTANA (SP-142) immunohistochemistry assay. Patients were categorized into three groups based to the percentage of the tumor area covered by PD-L1 on TIICs: IC0 (&lt;1%), IC1 (≥1% and &lt;5%), and IC2/3 (≥5%). Positive PD-L1 was defined as IC2/3 (≥5%). Kaplan–Meier survival analysis was used to illustrate recurrence-free survival (RFS), and Cox proportional hazard models were used to identify predictive factors of tumor recurrence.ResultsWithin the cohort, the proportions of PD-L1 IC0, IC1, and IC2/3 were 21.7%, 23.9%, and 54.4%, respectively. At follow-up (mean 31.3 months), tumor recurrence was identified in 49 patients (53.3%). Using multivariable analysis, tumor stage (pT4; P=0.005), positive lymph nodes (P=0.021), and positive PD-L1 on TIICs (P=0.010) were independent predictors of tumor recurrence. The 2- and 3-year RFS rates were 67.7% and 64.2% in negative PD-L1 on TIICs, while 27.8% and 22.3% in positive PD-L1 on TIICs, respectively.ConclusionsPositive PD-L1 on TIICs was significantly associated with poorer RFS in “high-risk” patients after RC without AC. Our results support the use of adjuvant immunotherapy in “high-risk” patients with positive PD-L1 on TIICs after RC.
Diagnosis of Invasive Meningioma Based on Brain-Tumor Interface Radiomics Features on Brain MR Images: A Multicenter Study
Authors: Xiao Dongdong , Zhao Zhen , Liu Jun , Wang Xuan , Fu Peng , Le Grange Jehane Michael , Wang Jihua , Guo Xuebing , Zhao Hongyang , Shi Jiawei , Yan Pengfei , Jiang Xiaobing 
Published: August 2021

BackgroundMeningioma invasion can be preoperatively recognized by radiomics features, which significantly contributes to treatment decision-making. Here, we aimed to evaluate the comparative performance of radiomics signatures derived from varying regions of interests (ROIs) in predicting BI and ascertaining the optimal width of the peritumoral regions needed for accurate analysis.MethodsFive hundred and five patients from Wuhan Union Hospital (internal cohort) and 214 cases from Taihe Hospital (external validation cohort) pathologically diagnosed as meningioma were included in our study. Feature selection was performed from 1,015 radiomics features respectively obtained from nine different ROIs (brain-tumor interface (BTI)2–5mm; whole tumor; the amalgamation of the two regions) on contrast-enhanced T1-weighted imaging using least-absolute shrinkage and selection operator and random forest. Principal component analysis with varimax rotation was employed for feature reduction. Receiver operator curve was utilized for assessing discrimination of the classifier. Furthermore, clinical index was used to detect the predictive power.ResultsModel obtained from BTI4mm ROI has the maximum AUC in the training set (0.891 (0.85, 0.932)), internal validation set (0.851 (0.743, 0.96)), and external validation set (0.881 (0.833, 0.928)) and displayed statistically significant results between nine radiomics models. The most predictive radiomics features are almost entirely generated from GLCM and GLDM statistics. The addition of PEV to radiomics features (BTI4mm) enhanced model discrimination of invasive meningiomas.ConclusionsThe combined model (radiomics classifier with BTI4mm ROI + PEV) had greater diagnostic performance than other models and its clinical application may positively contribute to the management of meningioma patients.
Effect and Safety of Therapeutic Regimens for Patients With Germline BRCA Mutation-Associated Breast Cancer: A Network Meta-Analysis
Authors: Jiang Ying , Meng Xiang-Yu , Deng Ning-Ning , Meng Chen , Li Lu-Hui , He Zi-Kang , Wang Xing-Yun , Song Zhe-Yao , Cui Rong-Jun 
Published: August 2021

PurposeBreast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis.MethodsPublic databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies.ResultsSeventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 – 0.79), platinum (HR: 0.45; 95% CI: 0.22 – 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 – 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 – 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo.ConclusionThe PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.
Bibliometric Analysis of Bronchopulmonary Dysplasia in Extremely Premature Infants in the Web of Science Database Using CiteSpace Software
Authors: Zhou Qin , Kong Hai-Bo , He Bao-Mei , Zhou Su-Ya 
Published: August 2021

Objectives: To review the literature related to bronchopulmonary dysplasia in extremely pre-mature infants, summarize research direction, and report trends.Methods: CiteSpace is a Java application which supports visual exploration with knowledge discovery in bibliographic databases. Relevant articles from 2008 to 2020 were retrieved from the Web of Science Core Collection database, and we extracted the following data: title, abstract, year, keywords, author, organization, journal and cited literature. We downloaded the data into CiteSpace (version 5.7.R3) to summarize countries, institutions, journals, and authors. We visualized the data with a knowledge map, collaborative network analysis, cluster analysis, and burst keyword analysis.Results: We identified 610 articles on bronchopulmonary dysplasia in extremely pre-mature infants. The United States had the most articles on this topic (302 articles), followed by Canada (49 articles) and Germany (44 articles). The top three institutions, high-yield journals, and authors were all from the United States. The most common keywords were neurodevelopmental disorders, active perinatal care, mechanical ventilation, inflammation, pulmonary hypertension, low-dose hydrocortisone, development, and patent ductus arteriosus.Conclusions: This study illustrates the trends and frontiers in the study of bronchopulmonary dysplasia in extremely pre-mature infants. The current research direction is to identify the risk factors in developing bronchopulmonary dysplasia in extremely pre-mature infants.