bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Sex-Specific Risk Scoring System for Predicting Cognitive Normal to Mild Cognitive Impairment (SRSS-CNMCI)
Authors: Luo Wen , Wen Hao , Ge Shuqi , Tang Chunzhi , Liu Xiufeng , Lu Liming 
Published: May 2021

Abstract
Objective: We aim to develop a sex-specific risk scoring system for predicting cognitive normal (CN) to mild cognitive impairment (MCI), abbreviated SRSS-CNMCI, to provide a reliable tool for the prevention of MCI.Methods: Participants aged 61-90 years old with a baseline diagnosis of CN and an endpoint diagnosis of MCI were screened from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database with at least one follow-up. Multivariable Cox proportional hazards models were used to identify risk factors associated with conversion from CN to MCI and to build risk scoring systems for male and female groups. Receiver operating characteristic (ROC) curve analysis was applied to determine the risk probability cutoff point corresponding to the optimal prediction effect. We ran an external validation of the discrimination and calibration based on the Harvard Aging Brain Study (HABS) database.Results: A total of 471 participants, including 240 women (51%) and 231 men (49%), aged 61 to 90 years, were included in the study cohort for subsequent primary analysis. The final multivariable models and the risk scoring systems for females and males included age, APOE ε4, Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). The scoring systems for females and males revealed C statistics of 0.902 (95% CI 0.840-0.963) and 0.911 (95% CI 0.863-0.959), respectively, as measures of discrimination. The cutoff point of high and low risk was 33% in females, and more than 33% was considered high risk, while more than 9% was considered high risk for males. The external validation effect of the scoring systems was good: C statistic 0.950 for the females and C statistic 0.965 for the males. Conclusions: Our parsimonious model accurately predicts conversion from CN to MCI with four risk factors and can be used as a predictive tool for the prevention of MCI.
Pseudogene HSPA7 is a Poor Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and Correlated With Immune Infiltrates
Authors: Ding Chunjin , He Rundong , Zhang Jinghan , Dong Zhan , Wu Jun 
Published: May 2021

Abstract
Background: Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer. Methods: Firstly,we used Logistic regression,the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the level of HSPA7 expressed in KIRC,then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival(OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC. Results: The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRCpatints.GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell.Conclusions: Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.
A Single Stage Spool Valve for the Pressure Compensator of a Variable Displacement Pump – Design, Dynamic Simulation and Comparative Study With A Real Pump
Authors: Mondal Nitesh , Saha Rana , Sanyal Dipankar 
Published: May 2021

Abstract
The study is focused on the design of a simplified spool valve to be incorporated in the pressure compensator of a variable displacement axial piston pump in order to perform a comparative study with a commercial pump having a two stage spool valve in its compensator. The design involves evaluation of the spool size and selection of spring from static equilibrium condition to satisfy cut-in and cut-off pressure. Following the development of dynamic model of the system, a design sensitivity analysis of the spool valve has been carried out through simulation to identify the critical sizes of the parameters, which affect the pump performance. By systematic design, it is possible to have a single stage spool valve controlled pressure compensator that can produce performance of the variable displacement axial piston pump at par with the similar commercially available pump.
Pt-Rh Alloy Catalysts for Hydrogen Generation developed by Direct Current/Pulse Method
Authors: bm praveen , Devendra Bharath K , S Tripathi V , DH Nagaraju , O Nayana K 
Published: May 2021

Abstract
Highly active Pt-Rh alloy catalyst coatings were developed by direct current (DC) and pulse current (PC) electrodeposition method for efficient hydrogen evolution reaction (HER) catalysts. The coatings were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) linear sweep voltammetry (LSV) studies. Pt-Rh alloy catalyst coatings showed almost similar behavior as pure platinum metal.The Pt-Rh coating were obtained by PC method showed low over potentialfor HER. Very low slope of 41.2 mV/dec is obtained represents the Volmer-Tafel mechanistic path way for HER process. Chronopotentiometry was conducted and amount of hydrogen collected during these experiments was 24 ml for PC method 75% duty cycle sample.
Levetiracetam Serum Concentrations in Pediatric Patients: Is There a Role in Clinical Decision Making?
Authors: Arslan Müjgan , Yılmaz Murat , Karaibrahimoğlu Adnan 
Published: May 2021

Abstract
Monitoring of levetiracetam is not frequently used in clinical practice. This study evaluated the LEV blood level concentrations, correlation with dose, and co-medication effect to decide the need for blood concentration monitoring in pediatric patients. The children with epileptic seizures on levetiracetam therapy, aged one month-18 years, were enrolled and evaluated for gender, age, body weight, daily drug dose, comedication, and drug concentration records. 57.9% of one hundred and forty patients were on monotherapy. The mean dose of LEV was 35.40 mg/kg/day, while the mean drug concentration was 14.06 μg/ mL. The correlation between the dose and the serum concentration in the polytherapy group was poorly significant, whereas it was positive and highly significant in the monotherapy group. The mean drug concentration was within the established reference range, but concentration monitoring revealed children with serum concentrations below and above the therapeutic range. All cases in our study had the typical range of drug dose per body weight with no side effects. Conclusion: We point out that monitoring is not practical for most patients. Due to its tolerability over an extensive concentration range, the clinical assessment remains the monitoring strategy for patients with epilepsy on LEV therapy.
A Machine-learning Signature Performs as Well as Experts' Consensus to Diagnose Pelvic Lymph Node Involvement in Bladder Cancer on [18F]-FDG PET/CT: A Pathology-controlled Study
Authors: GIRARD Antoine , DERCLE Laurent , VILA-REYES Helena , SCHWARTZ Lawrence H. , GIRMA Astrid , BERTAUX Marc , RADULESCU Camelia , LEBRET Thierry , DELCROIX Olivier , ROUANNE Mathieu 
Published: May 2021

Abstract
The authors have requested that this preprint be removed from Research Square.
Astragaloside Iv Suppresses Histamine-induced Inflammatory Factors and MUC5AC Overproduction in Nasal Epithelial Cells via Regulation of Inflammation-related Genes
Authors: Guo Jie , Xu Shuai 
Published: May 2021

Abstract
Allergic rhinitis (AR) is a symptomatic allergic disease that leads to severe inflammation. Astragaloside IV (AS-IV) is a primary active component of Astragalus membranaceus and exerts immune-regulation and anti-inflammatory effects. However, the pharmacological effect of AS-IV in the nasal epithelial cells (NECs) has not been reported. The present study aimed to assess the effect of AS-IV on inflammatory cytokines and mucin 5 subtype AC (MUC5AC) overproduction in histamine (His)-stimulated NECs and its underlying mechanism. NECs were stimulated with or without His for 24 h in the absence or presence of AS-IV. The levels of inflammatory cytokines including IL-6, IL-8, MCP-1, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUC5AC were assayed. Our findings indicated that AS-IV inhibited His-evoked release and expression of inflammatory cytokines and MUC5AC in NECs. RNA-SEQ analyses indicated the significant changes in expression levels involved in inflammation genes upon treatment of His-induced NECs with AS-IV. Our findings indicated that AS-IV inhibited His-evoked inflammatory cytokines secretion and MUC5AC overproduction in NECs, which were partly mediated by regulation of inflammation-related genes. AS-IV might be a therapeutic agent for the treatment of AR.
Risk Factors for Lymphedema After Breast Surgery: a Prospective Cohort Study in the Era of Sentinel Lymph Node Biopsy
Authors: Huertas Sira Salinas , Luzardo-González A. , Vazquez-Gallego S. , Pernas Sonia , Falo C. , Pla MJ. , Gil-Gil M. , Beranuy-Rodriguez M , Perez-Montero H. , Gomila-Sancho M. , Manent-Molina N. , Arencibia-Domínguez A. , Gonzalez-Pineda B. , Tormo-Collado F. , Ortí-Asencio M. , Terra J. , Martinez-Perez E. , Benítez-Segura A. , Campos-Delgado M. , Fernández-Montolí ME. , Valverde-Alcántara Y. , Rodriguez A. , Campos-Delgado G. , Guma A. , Ponce-Sebastià J. , Planas-Balagué R. , Catasús-Clavé M.LL , García-Tejedor A. 
Published: May 2021

Abstract
Introduction: We aimed to investigate the incidence of lymphedema after breast cancer treatment, to analyze the risk factors involved, and to improve existing protocols for the prevention of lymphedema. Patients and methods: This was a prospective cohort study of 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, as well as local and systemic therapies, were analyzed as possible risk factors for lymphedema. Results: In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1–54 months). Most cases of lymphedema cases appeared in the first 2 years. 13.9% developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92–18.16) and 3.9 (1.60–9.49), respectively. Conclusions: The main risk factors for lymphedema were the most radical surgeries (ALND and mastectomy), while the risk associated with these appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND for at least two years, where these risk factors are recognized, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.
Diagnosis and Surgical Treatment of Intradiaphragmatic Extralobar Pulmonary Sequestration: a Report of 10 Cases
Authors: Han Xu , Gao Yue , Tan Zheng 
Published: May 2021

Abstract
Background Intradiaphragmatic extralobar pulmonary sequestration(IDEPS) is a rare type of pulmonary sequestration (PS) and has been reported in very few studies. The purpose of this study is to access diagnosis and operative treatment of an IDEPS.Methods Patients with PS who were diagnosed and treated in our center from January 2015 to December 2020 were retrospectively analyzed, in order to identify patients with IDEPS. Clinical datas regarding diagnosis, surgical procedures and outcomes were documented.Results From January 2015 to December 2020, 215 patients with PS were surgically treated in our center, including 87 patients with extralobar pulmonary sequestration(EPS). 10 cases were identifed as IDEPS ( 2 males, 8 females; age, 5 months to 21 months). Prenatal ultrasounds and enhanced computed tomography (CT) showed the presence of IDEPS in 4 cases and 7 cases, respectively, and a three-dimensional (3D) reconstruction software was perfectly performed to identify the location of the lesions in 3 cases. The surgeries were smoothly performed by laparoscopic surgery in 1 case, video-assisted thoracic surgery (VATS) in 5 cases(Group 1) and Da Vinci robot-assisted thoracoscopic surgery(DVRATS) in 4 cases(Group 2). In Group 1 (5 females; the mean age, 8.0 months), the average operative duration, intraoperative blood loss volume, length of stay after operation, and postoperative thoracic catheter indwelling duration were 48 minutes, 3.8ml, 6.4 days and 2.2 days, respectively. That of Group 2(1 male, 3 females; the mean age, 9.5 months) were 80 minutes, 3.5ml, 4.3 days and 1.5 days, respectively. The IDEPS cases who followed up rang from 3 months to 36 months were included in this retrospective study and no side effect had appeared.Conclusions It’s challenging to diagnose an IDEPS through prenatal ultrasound or CT, and a 3D reconstruction software was proved to be capable to assist on the assessment of an IDEPS. We suggested early surgery to removel of an IDEPS, and the best path was accessing the mass from the chest. DVRATS or VATS for the treatment of an IDEPS is safe, feasible and effective. Furthermore, compared with VATS, DVRATS is 3D magnified view, more flexibility and precision.
miR-203a-3p and MMP-2 protein are highly expressed in circulating tumor cells from patients with pancreatic carcinoma
Authors: Tarazona José Gabriel Rodríguez , Abdallah Emne Ali , Flores Bianca C. T. , Coutinho-Camillo Cláudia Malheiros , Marchi Fabio Albuquerque , Chinen Ludmilla Thomé Domingos 
Published: May 2021

Abstract
Objectives: to explore the morphological, molecular and phenotypical characteristics of circulating tumor cells (CTCs) from blood of patients with pancreatic carcinoma, and to correlate the findings with response to treatment, progression-free survival, overall survival (OS) and deep vein thrombosis (DVT). Methods: peripheral blood (10mL) was analyzed before the beginning of treatment, and after 60 and 120 days. CTCs were detected by ISET® and characterized by immunocytochemistry. For miRNAs analysis, peripheral leukocytes from the same patients and healthy individuals (controls) were collected in parallel at baseline. The expression of miRNAs was evaluated (in pool) using TaqMan™ Array Human MicroRNA Cards v2.0. Results: there were included 9 patients. The proteins MMP2 and TGFβ-RI were highly expressed (77.7%) in CTCs at baseline; at the first follow-up, MMP2 was predominant (80%) and at second follow-up, MMP2 and vimentin were predominant (50%). Circulating tumor microemboli (CTM) were found in two patients and both presented DVT. The miR-203a-3p was highly expressed in CTCs. miR-203a-3p is involved in the stimulation of epithelial-to-mesenchymal transition (EMT) and related to worse OS in pancreatic cancer (TCGA data). Conclusion: Due to the low number of patients and short follow-up, we did not observe a correlation between CTCs and response to treatment. However, there was a correlation between CTM and DVT as also miR-203a-3p was highly expressed in CTCs, corroborating the findings of EMT proteins. This study opens perspectives concerning the dynamic change in the pattern of proteins expressed along treatment and the use of miRNAs as new targets in pancreatic carcinoma.
Hypoxia-Responsive Nanoreactors to Amplify Oxidative Damage Through Multiple Cascaded Pathways for Promoting Photodynamic/Ferroptosis-Induced ROS Generation and Simultaneously Disrupting Tumor Antioxidant Defense System
Authors: Wang Xiaoyan , Wu Ming , Zhang Xiaolong , Li Feida , Zeng Yongyi , Lin Xinyi , Liu Xiaolong , Liu Jingfeng 
Published: May 2021

Abstract
Background: Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current systems still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy.Results: The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo.Conclusion: BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.
Machine learning-based prediction of cognitive trajectories among middle-aged and elderly Chinese adults
Authors: Wu Yafei , Jia Maoni , Xiang Chaoyi , Lin Shaowu , Jiang Zhongquan , Fang Ya 
Published: May 2021

Abstract
Background

Cognition represents heterogeneous in trajectories with increasing age. Early identification of such trend is essential for the prevention of high risk population related to cognition decline. This study aimed to explore the heterogeneity and determinants of cognitive trajectories, and construct prediction models for distinguishing cognitive trajectories among the middle-aged and elderly Chinese people at a community level.
Methods

Data was retrospectively collected from the China Health and Retirement Longitudinal Study with a consecutive survey in 3 waves (2011, 2013, 2015). The Mini-mental State Examination (MMSE) scale was used for cognitive measurement. The heterogeneity of cognitive trajectories was identified through mixed growth model, and the determinants of cognitive trajectories were analyzed by logistic regression. Machine learning (ML) algorithms, namely logistic regression (LR), support vector machine (SVM), and random forest (RF), combined with recursive feature elimination were used to predict cognitive trajectories using epidemiological variables. Area under the receiver operating characteristic curve (AUROC) and brier score were used to assess discrimination and calibration, respectively.
Results

Three cognitive trajectories were identified: “persistently-high” (PH, 83.3%) class with a high cognitive score in baseline and remained high subsequently, “medium-decrease” (MD, 6.6%) class with a medium cognitive score in baseline and a rapid decline subsequently, “low-increase” (LI, 10.1%) with the lowest baseline cognitive score and a rapid growth subsequently. For classification of PH vs. LI and MD vs. LI, the AUROCs of three ML methods were almost larger than 0.90, and brier scores were almost less than 0.10. For PH vs. MD, ML performed less well with the maximum AUROCs close to 0.68, while the calibration was still good. The initial MMSE score was the most significant predictors for distinguishing MD vs. LI and PH vs. LI, while age was the most important predictors in distinguishing MD vs. PH.
Conclusions

Prediction of cognitive trajectories and identification of its key predictors are of great significance for understanding the heterogeneity of cognitive trajectories as well as interventions for cognitive decline.
Machine Learning-Based Direct Solver for One-To-Many Problems on Temporal Shaping of Electron Beams
Authors: Wan Jinyu , Jiao Yi , Wu Juhao 
Published: May 2021

Abstract
To control the temporal profile of an electron beam to meet requirements of various advanced scientific applications, a widely-used technique is to manipulate the dispersion terms which turns out to be one-to-many problems. Due to their intrinsic one-to-many property, current popular stochastic optimization approaches on temporal shaping are not very effective, for being trapped into local optima or suggesting only one solution. Here we propose a real-time solver for one-to-many problems of temporal shaping, with the aid of a semi-supervised machine learning method, the conditional generative adversarial network (CGAN). We demonstrate that the CGAN solver can learn the one-to-many dynamics and is able to accurately and quickly predict the required dispersion terms for different custom temporal profiles. This machine learning-based solver overcomes the limitation of the stochastic optimization methods and is expected to have the potential for wide applications to one-to-many problems in other scientific fields.
Fine Structure Constant derived from Principle Theory.
Authors: Geilhaupt Manfred 
Published: May 2021

Abstract
Derivation of mass (m), charge (e) and fine structure constant (FSC) from theory are unsolved problems in physics up to now. Neither the Standard Model (SM) nor the General theory of Relativity (GR) has provided a complete explanation for the existence of the rest mass, i.e. restmass of the electron. The question “of what is rest mass” is therefore still essentially unanswered. We will show that the combination of two Principle Theories, General Relativity and Thermodynamics (TD), is able to derive the restmass of an electron (m) which surprisingly depends on the (Sommerfeld) FSC. Same to the charge (e).