bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proteomic Platform to Identify Off-Target Proteins Associated with Therapeutic Modalities that Induce Protein Degradation or Gene Silencing
Authors: Liu Xin , Zhang Ye , Ward Lucas D. , Yan Qinghong , Bohnuud Tanggis , Hernandez Rocio , Lao Socheata , Yuan Jing , Fan Fan 
Published: March 2021

Abstract
Novel modalities such as Proteolysis Targeting Chimera (PROTAC) and RNA interference (RNAi) have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate abundance of off-target proteins. The first part of the study involves selecting a panel of off-target proteins and a platform of cell lines using evidence from genetics and pharmacology. This process yielded 2,813 proteins, forming the basis of a panel that we refer to as the “selected off-target proteome” (SOTP). An iterative algorithm was then used to identify appropriate cell lines. Four human cell lines out of 932 were selected that, collectively, expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins of interest in the 4 selected cell lines. Among over 10,000 quantifiable proteins identified, 1,828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing rationale selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.
Development and Validation of a Risk Prediction Model for Postoperative Pneumonia in Adult Patients Undergoing Stanford Type a Acute Aortic Dissection Surgery: A Case Control Study
Authors: Wang Dashuai , Huang Xiaofan , Wang Hongfei , Chen Xing , Le Sheng , Du Xinling 
Published: March 2021

Abstract
BackgroundPneumonia is a common complication after Stanford type A acute aortic dissection surgery (AADS) and contributes significantly to morbidity, mortality, and length of stay. The purpose of this study was to identify independent risk factors associated with pneumonia after AADS and to develop and validate a risk prediction model.MethodsAdults undergoing AADS between 2016 and 2019 were identified in a single-institution database. Patients were randomly divided into training and validation sets at a ratio of 2:1. Preoperative and intraoperative variables were included for analysis. A multivariate logistic regression model was constructed using significant variables from univariate analysis in the training set. A nomogram was constructed for clinical utility and the model was validated in an independent dataset.ResultsPostoperative pneumonia developed in 170 of 492 patients (34.6%). In the training set, multivariate analysis identified seven independent predictors for pneumonia after AADS including age, smoking history, chronic obstructive pulmonary disease, renal insufficiency, leucocytosis, low platelet count, and intraoperative transfusion of red blood cells. The model demonstrated good calibration (Hosmer-Lemeshow χ2 = 3.31, P = 0.91) and discrimination (C-index = 0.77) in the training set. The model was also well calibrated (Hosmer-Lemeshow χ2 = 5.73, P = 0.68) and showed reliable discriminatory ability (C-index = 0.78) in the validation set. By visual inspection, the calibrations were good in both the training and validation sets.ConclusionWe developed and validated a risk prediction model for pneumonia after AADS. The model may have clinical utility in individualized risk evaluation and perioperative management.Clinical Trial Registry NumberChiCTR1900028127.
Disentangling Predictive Processing in the Brain: A Meta-analytic Study in Favour of a Predictive Network
Authors: Ficco Linda , Mancuso Lorenzo , Manuello Jordi , Teneggi Alessia , Liloia Donato , Duca Sergio , Costa Tommaso , Kovacs Gyula Zoltán , Cauda Franco 
Published: March 2021

Abstract
According to the predictive coding (PC) theory, the brain is constantly engaged in predicting its upcoming states and refining these predictions through error signal. Despite extensive research has investigated the neural bases of this theory, to date no previous study has systematically attempted to define the neural mechanisms of predictive coding across studies and sensory channels, focussing on functional connectivity. In this study, we employ a coordinate-based meta-analytical approach to address this issue. We first use the Activation Likelihood Estimation (ALE) algorithm to detect spatial convergence across studies, related to prediction error and encoding. Overall, our ALE results suggest the ultimate role of the left inferior frontal gyrus and left insula in both processes. Moreover, we employ a task-based meta-analytic connectivity method (Seed-Voxel Correlations Consensus). This technique reveals a large, bilateral predictive network, which resembles large-scale networks involved in task-driven attention and execution. In sum, we find that: i) predictive processing seems to occur more in certain brain regions than others, when considering different sensory modalities at a time; ii) there is no evidence, at the network level, for a distinction between error and prediction processing.
Quantitative Analysis of Neuronal Mitochondrial Movement Reveals Patterns Resulting from Neurotoxicity of Rotenone and 6-hydroxydopamine
Authors: Simões Rui F. , Pino Rute , Moreira-Soares Maurício , Kovarova Jaromira , Neuzil Jiri , Travasso Rui , Oliveira Paulo J. , Cunha-Oliveira Teresa , Pereira Francisco B. 
Published: March 2021

Abstract
Alterations in mitochondrial dynamics, including their intracellular trafficking, are common early manifestations of neuronal degeneration. However, current methodologies used to study mitochondrial trafficking events rely on parameters that are mostly altered in later stages of neurodegeneration. Our objective was to establish a reliable computational methodology to detect early alterations in neuronal mitochondrial trafficking. We propose a novel quantitative analysis of mitochondria trajectories based on innovative movement descriptors, including straightness, efficiency, anisotropy, and kurtosis. Using biological data from differentiated SH-SY5Y cells treated with the mitochondrial toxicants 6-hydroxydopamine and rotenone, we evaluated time- and dose-dependent alterations in trajectory descriptors. MitoTracker Red CMXRos-labelled mitochondria movement was analyzed by total internal reflection fluorescence microscopy followed by computational modelling to describe the process. This innovative analysis of mitochondria trajectories, based on the aforementioned trajectory descriptors, provides insights into mitochondrial movement characteristics and can be a consistent and sensitive method to detect alterations in mitochondrial trafficking occurring in the earliest time points of neurodegeneration.
Efficacy and safety of CT-P59 plus standard of care: a phase 2/3 randomized, double-blind, placebo-controlled trial in outpatients with mild-to-moderate SARS-CoV-2 infection
Authors: Eom Joong Sik , Ison Michael , Streinu-Cercel Anca , Săndulescu Oana , Preotescu Liliana-Lucia , Kim Yeon-Sook , Kim Jin Yong , Cheon Shin Hyea , Jang Young Rock , Lee Sang Joon , Kim Sung Hyun , Chang Ilsung , Suh Jee Hye , Lee Seul Gi , Kim Mi Rim , Chung Da Rae , Kim Han Na , Streinu-Cercel Adrian 
Published: March 2021

Abstract
CT-P59, a monoclonal antibody with potent neutralizing activity against severe acute respiratory syndrome coronavirus 2, may ameliorate symptoms and prevent hospitalization in outpatients with mild-to-moderate disease. We report findings from part one of a two-part randomized, placebo-controlled, double-blind study (NCT04602000; EudraCT: 2020-003369-20). Outpatients with mild-to-moderate COVID-19 received a single dose of CT-P59 40 mg/kg (n=101), CT-P59 80 mg/kg (n=103), or placebo (n=103). Median (95% confidence interval [CI]) time to conversion to negative RT-qPCR result (coprimary endpoint) was 12.8 days (9.00–12.84) with CT-P59 40 mg/kg, 11.9 days (8.94–12.91) with CT-P59 80 mg/kg, and 12.9 days (12.75–13.99) with placebo. Median (95% CI) time to clinical recovery (coprimary endpoint) was 5.4 days (3.97–6.78) with CT-P59 40 mg/kg, 6.2 days (5.53–7.85) with CT-P59 80 mg/kg, and 8.8 days (6.72–11.73) with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with CT-P59 40 mg/kg (4.0% [1.6–9.7%]) and CT-P59 80 mg/kg (4.9% [2.1–10.9%]) versus placebo (8.7% [4.7–15.8%). CT-P59 was well tolerated and no serious treatment-emergent adverse events or deaths occurred. In summary, CT-P59 accelerated viral and clinical recovery from COVID-19 and was well tolerated in patients with mild-to-moderate infection.
Cumulative Exposure Characteristics of Vegetable Farmers Exposed to Chlorpyrifos in Central Java – Indonesia; A Cross-sectional Study
Authors: Liem Jen Fuk , Mansyur Muchtaruddin 
Published: March 2021

Abstract
BackgroundAgriculture is a major economic sector in Indonesia. Chemical pesticides are widely being used in agriculture for the control of the pest. There is a growing concern that pesticide exposure, particularly chlorpyrifos (CPF) exposure combined with other occupational characteristics that determine the level of exposure, can lead to further health impacts for farmers. Our objective was to evaluate the cumulative exposure characteristics among farmers exposed to CPF using a validated algorithm.MethodsWe conducted a cross-sectional study of 152 vegetable farmers aged 18-65 who actively used CPF for at least one year in Central Java, Indonesia. Subject characteristics were obtained using a structured interviewer-administered questionnaire addressed for sociodemographic and work-related characteristics. The cumulative exposure level (CEL) was measured as a function of the intensity level of pesticide exposure (IL), lifetime years of pesticide use and the number of days spraying per years. CEL then classified into two groups, high and low exposure group. The difference in characteristics of the study population was measured using Chi-square, independent-t or Mann-Whitney test. Association between CEL and its characteristics variables were performed by multiple linear regression.ResultsSeventy-one subjects (46.7%) were classified as the high exposure group. The use of multiple pesticide mixtures was common among our study population, with 94% of them using 2 or more pesticides. 73% reported direct contact with pesticides, and over 80% reported being splashed or spilt during preparation or spraying activity. However, we found that the proportion of proper personal protective equipment (PPE) use in our subjects was low. Higher volume of mixture applied (p < 0.001) and broader acres of land (p = 0.001) were associated with higher cumulative exposure level, while using the long sleeve and long trousers (p < 0.05) during pesticide spraying were associated with lower cumulative exposure after adjusted for age and gender.ConclusionsThese findings indicate a lack of knowledge and understanding of the proper use of pesticides. Thus, we recommend comprehensive training on pesticide use and encourage proper PPE to reduce the exposure level.
Adsorption of Cellulases on BHKP Fibers during Pretreatment for MFC Film Preparation
Authors: Zhang Zhengjian , Wang Xiaojuan , Yan Hongyue , Qiu Lixin 
Published: March 2021

Abstract
Adsorption of cellulase on fibers is a key factor in determining its efficiency on fiber treatment and microfibrillated cellulose (MFC) preparation. Different adsorption behavior, treatment efficiency and performance of MFC and MFC film were observed due to the different properties of cellulases. Herein, bleached eucalyptus kraft pulp (BHKP) was pretreated by complex cellulase (D cellulase) and endocellulase (R cellulase) with different dosages for MFC preparation. Enzyme activity, adsorption ratio, adsorption kinetics and adsorption thermodynamic of the two cellulases were comprehensively studied, and the impacts of the cellulase pretreatment on the properties of MFC and MFC film were investigated. The results showed that D cellulase possessed higher adsorption ratio than R cellulase, but R cellulase demonstrated higher adsorption rate than D cellulase. High temperature discouraged the adsorption of the two cellulases because of their exothermic natures. The crystallinity index (CrI), specific surface area (SSA) and morphology of MFC were tuned by the combination of two cellulases at different dosages. The CrI of MFC treated by D cellulase and R cellulase increased from 40.45% to 66.50% and 66.67% respectively when the cellulase dosage was 10 U/g. The elongation at break (E) and tensile strength (TS) of MFC film treated by D cellulase were decreased first and then increased slightly, but the MFC film treated by R cellulase decreased continuously. The MFC film prepared by D cellulase possessed the best barrier property at 20 U/g and the corresponding oxygen permeability coefficient was 4.37×10-14 cm3·cm/cm2·s·Pa. However, the oxygen permeability coefficient of MFC film pretreated by R cellulase at a dosage of 10 U/g was 4.13×10-14 cm3·cm/cm2·s·Pa. This work shows that R cellulase was more suitable than D cellulase for BHKP pretreatment to prepare MFC film.
Adaptive Neural Consensus Tracking Control for Multi-agent Systems with Unknown State and Input Hysteresis
Authors: Lin Zhuangbi , Liu Zhi , Zhang Yun , Chen C.L.Philip 
Published: March 2021

Abstract
An indirect adaptive consensus control method is presented for MASs with Unknown Bouc-Wen hysteresis states and input. All states of MASs are measured by sensors subjected to hysteresis. In order to reduce the effect of hysteresis with multi-value and rate-dependent characteristics, an adaptive compensated scheme is proposed. NNs are introduced to approximate the time-varying control gain which is coupled by input hysteresis and states hysteresis. The parameters of inverse compensation model are approximated by adaptive laws. The proposed control scheme can guarantee that the consensus errors of followers converge to a predefined interval of zero asymptotically. In addition, the transient performance of MASs can be further ensured. A simulation example is included to verify the effectiveness of the presented control approach.
One-stage posterior laminectomy with instrumented fusion and foraminotomy for cervical ossification of posterior longitudinal ligament with radiculopathy pain
Authors: Su Bao , Shen Jieliang , Luo Xiaoji , Quan Zhengxue , Jiang Dianming , Peng Xiaohua , Tang Ke 
Published: March 2021

Abstract
ObjectiveTo explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs.MethodsBetween January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF Group (laminectomy with instrumented fusion without foraminotomy) and LFF Group (laminectomy with instrumented fusion and foraminotomy). ໿Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Achievement of fusion and changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of spinal cord was evaluated based on postoperative MRI.ResultsAll the 48 patients were followed up for 24-42months with an average follow-up time of 31.1 ± 5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 case (83.3%) with 1 intervertebral foramens enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, ໿postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The ໿VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two group in terms of C2–C7 SVA, cervical lordosis, ໿focal angulation at the foraminotomy segment and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group.ConclusionsOne-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.
Relationship of Body Fat and Left ventricular hypertrophy with the Risk of All-cause Death in Patients with Coronary Artery Disease
Authors: Huang Baotao , Yang Lu , Yang Bosen , Huang Fangyang , Xiao Qianfeng , Pu Xiaobo , Peng Yong , Chen Mao 
Published: March 2021

Abstract
Background and aimsLeft ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. However, little is known about the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD).MethodsIn this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using formulas. Higher body fat was defined as the percentage of body fat was greater than 75th percentile. LVH was defined according to guidelines’ definition. Patients were divided into four groups: group 1, lower body fat and no LVH; group 2, lower body fat and LVH; group 3, higher body fat and no LVH; group 4, higher body fat and LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.ResultsOver 2.2 years, there were 120 deaths. Patients with higher body fat and no LVH (group 3) had similar risk of death (adjusted HR 1.83, 95%CI 1.00-3.38, P = 0.054) compared to the reference group (group 1), while patients with lower body fat and LVH (group 2) had the highest risk (adjusted HR 2.15, 95%CI 1.26–3.64, P = 0.005) of death. The results were robust after different degree of adjustment.ConclusionCertain amount of BF was not associated with increased risk of all-cause death in patients with CAD, even seems protective in those concomitant with LVH.
Investigation of Surface Quality in Cost of Goods Manufactured (COGM) method of µ-Al2O3 Powder-Mixed-EDM Process on Machining of Ti-6Al-4V
Authors: Taherkhania Aboulfazl , Ilani Mohsen Asghari , Ebrahimi Faramarz , Nguyen Phan Huu , Tien Long Banh , Van Dong Pham , Chi Tam Nguyen , Duc Minh Nguyen , Van Duc Nguyen 
Published: March 2021

Abstract
It is very essential to form such high stregth and hard-to-cut materials by using modern machining methods. It is important to introduce the efforts on modification of the process for improving the machining quality. In the present investigation, an effort was made to analyze the effects of micro size aluminium particles mixed dielectric medium under different powder concentration on machining titanium alloy in electro erosion process. The response-surface-methodology(RSM) based algorithm was utilized to analyze the performance measures by considering machinning time with Cost of Goods Manufactured (COGM) method in PMEDM process. It was found that the micron size powders can significantly help to enhance the surface quality of the Ti-6Al-4V surface during machining in EDM process. The presence of carbon, oxygen elements and the formation of surface oxides and carbides has been found due to the decomposition of dielectric fluid in PMEDM process. The lower deep cavities and uniform machining surface have been produced with the aluminum oxide powder EDM process owing to lower surface cracks density, conductivity. To sum up, investigation and comparison of surface scanning showed that this setting has been implied could be considered by the industries needs more precision.
Protocol for a randomized controlled trial of pre-pregnancy lifestyle intervention to reduce recurrence of gestational diabetes: Gestational Diabetes Prevention/Prevención de la Diabetes Gestacional
Authors: Phelan Suzanne , Jelalian Elissa , Coustan Donald , Castorino Kristin , Caughey Aaron , Shields Laurence , Hagobian Todd , Muñoz-Christian Karen , Schaffner Andrew , Heaney Casey , McHugh Angelica , Wing Rena 
Published: March 2021

Abstract
BackgroundGestational diabetes mellitus (GDM) is associated with several maternal complications in pregnancy, including preeclampsia, preterm labor, need for induction of labor, and cesarean delivery as well as increased long-term risks of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM raises the risk for complications in offspring as well, including stillbirth, macrosomia, and birth trauma and long-term risk of metabolic disease. One of the strongest risk factors for GDM is the occurrence of GDM in a prior pregnancy. Preliminary data from epidemiologic and bariatric surgery studies suggest that reducing body weight before pregnancy can prevent development of GDM, but no adequately powered trial has tested the effects of a maternal lifestyle intervention before pregnancy to reduce body weight and prevent GDM recurrence.MethodsThe principal aim of Gestational Diabetes Prevention/Prevención de la Diabetes Gestacional is to determine whether a lifestyle intervention to reduce body weight before pregnancy can reduce GDM recurrence. This two-site trial targets recruitment of 252 women with overweight and obesity who have previous histories of GDM and who plan to have another pregnancy in the next 1–3 years. Women are randomized within site to a comprehensive pre-pregnancy lifestyle intervention to promote weight loss with ongoing treatment until conception or an educational control group. Participants are assessed preconceptionally (at study entry, after 4 months, and at brief quarterly visits until conception), during pregnancy (at 26 weeks’ gestation) and at 6 weeks postpartum. The primary outcome is GDM recurrence and secondary outcomes include fasting glucose, biomarkers of cardiometabolic disease, prenatal and perinatal complications, and changes over time in weight, diet, physical activity and psychosocial measures.DiscussionGestational Diabetes Prevention /Prevención de la Diabetes Gestacional is the first randomized controlled trial to evaluate the effects of a lifestyle intervention delivered before pregnancy to prevent GDM recurrence. If found effective, the proposed lifestyle intervention could lay the groundwork for shifting current treatment practices towards the interconception period and provide evidence-based preconception counseling to optimize reproductive outcomes and prevent GDM and associated health risks.Trial registrationClinicalTrials.gov Identifier: NCT02763150