bluuebunny/crossref_metadata_2025 huggingface dataset:
CLEC10A is a Potential Prognostic Biomarker and Immune Regulator of Tumor Microenvironment in Breast Cancer
Authors: He Jincheng , Jiang Lei , Wang Jun , Min Guangtao , Wang Xiangwen , Chen Wei , Wang Hongpeng , Yao Nan
Published: March 2021

The communication between tumor cells and immune cells influences the ecology of the tumor microenvironment in breast cancer, as well as the disease progression and clinical outcome. The aim of this study was to investigate the prognostic value of the immunomodulatory factor CLEC10A in breast cancer. We applied the CIBERSORT and ESTIMATE calculation methods to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal components in 1053 BRCA cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, CLEC10A was identified as a prognostic factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that CLEC10A expression was negatively correlated with the clinical pathologic characteristics (age, clinical stage) and positively correlated with survival of BRCA patients. Gene set enrichment analysis (GSEA) showed that genes in the high CLEC10A expression group were mainly enriched in immune-related activities. Genes in the low CLEC10A expression group were enriched in biochemical functions. CIBERSORT analysis of the proportion of TICs revealed that Macrophages M1, B cells memory, B cells naive, T cells CD4+ memory activated, T cells CD8+, and T cells gamma delta were positively correlated with CLEC10A expression, and Macrophages M0, Macrophages M2, Neutrophils, and NK cells resting were positively correlated with CLEC10A expression was negatively correlated, suggesting that CLEC10A may be an important factor in the immune regulation of the tumor microenvironment, especially in mediating the anti-tumor immune response of tumor-infiltrating immune cells at the tumor initiation stage. Therefore, CLEC10A expression may contribute to the prognosis of BRCA patients and provide a new idea for the immunotherapy of BRCA.
Analysis of Equivalent Thickness of Geological Media for Lab-scale Study of Radon Exhalation
Authors: Hong Changshou , Yang Yini , Wang Hong , Liu Yong , Li Xiangyang , Lei Bo , Lan Ming , Chen Yifan , Dai Xingwang
Published: March 2021

Geological media are widely distributed in nature. Lab-scale tests are frequently employed in radon studies for these media. Thus, it is critical to find the thickness of the medium at an experimental scale that is equivalent to the medium thickness in a real geological system. Based on the diffusion–advection transport of radon, theoretical models of the surface radon exhalation rate for homogeneous semi-infinite and finite-thickness systems were derived (denoted as Jse and Jfi, respectively). Analysis of the equivalency of Jse and Jfi was subsequently carried out by introducing several dimensionless parameters, including the ratio of the exhalation rates for the semi-infinite and finite-thickness models, ε, and the number of diffusion lengths required to achieve a desired ε value, n. The results showed that when radon transport in geological media is dominantly driven by diffusion, if n > 3.6626, then ε > 95% (and if n > 5.9790, then ε > 99.5%). When radon migration is dominantly driven by advection, if n > 2.5002, then ε > 95% (and if n > 4.0152, then ε > 99.5%). Therefore, if the thickness of the geological media (x0) is greater than a certain n times the radon diffusion length of the media (L), the media can be modeled as semi-infinite. To validate the model, a pure radon diffusion experiment (no advection) was developed using uranium mill tailings, laterite, and radium-bearing rocklike material with different thicknesses (x0). The theoretical model was demonstrated to be reliable and valid. This study provides a basis for determining the appropriate thickness of geological media in lab-scale experiments of radon exhalation.
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

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

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

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

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

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

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

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

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

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

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

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

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
Activation of Cx-43 Hemichannels Induces the Generation of Ca2+-Oscillations in White Adipocytes and Stimulates Lipolysis.
Authors: Turovskaya Maria , Turovsky Egor
Published: March 2021

With fluorescence microscopy, it was revealed that a decrease in the concentration of extracellular calcium ([Ca2+]ex) results in two types of Ca2+-responses in white adipocytes: Ca2+-oscillations and transient Ca2+-signals. Activation of connexin hemichannels is involved in the mechanism of generation of Ca2+-oscillations, since the blockers of connexin hemichannels - carbenoxolone, octanol and proadifen, as well as Cx43 gene knock-down lead to complete suppression of these signals. TIRF microscopy confirmed activation of Cx-43 in response to the reduction of [Ca2+]ex. In response to the activation of Cx-43, the secretion of ATP-containing vesicles from adipocytes occurs. And this ATP release is suppressed in adipocytes along with the Cx43 gene knock-down and is inhibited by Bafilomycin A1, a vacuolar ATPase inhibitor. At the level of intracellular signaling, the generation of Ca2+-oscillations in white adipocytes in response to a decrease in [Ca2+]ex takes place due to the mobilization of Ca2 + ions from the thapsigargin-sensitive Ca2+-pool in the endoplasmic reticulum via IP3R as a result of the activation of P2Y1 purinergic receptors and the phosphoinositide signaling pathway. Such paracrine activation of white adipose tissue in response to the opening of Cx43 hemichannels leads to local signal propagation and regulation of gene expression. At 24 hours after activation of Cx-43 and generation of Ca2+-oscillations in white adipocytes, there is a change in the expression of key genes involved in the regulation of lipolysis, which is accompanied by a decrease in the number of adipocytes that contained lipid droplets. Meanwhile, inhibition or knock-down of Cx-43 leads to inhibition of lipolysis and accumulation of lipid droplets. In this study, we elucidate and research the mechanism of generation of Ca2+-oscillations in white adipocytes in response to decreased concentration of Ca2 + ions in the external environment and show the correlation between periodic Ca2+-modes and lipolysis/lipogenesis balance regulation.
Insulin Resistance and Muscle Weakness Are Synergistic Risk Factors for Silent Lacunar Infarcts: the Bunkyo Health Study: a Cross Sectional Study
Authors: someya Yuki , Tamura Yoshifumi , Kaga Hideyoshi , Sugimoto Daisuke , kadowaki Satoshi , Suzuki Ruriko , Aoki Shigeki , Hattori Nobutaka , Motoi Yumiko , Shimada Kazunori , Daida Hiroyuki , Ishijima Muneaki , Kaneko Kazuo , Nojiri Shuko , Kawamori Ryuzo , Watada Hirotaka
Published: March 2021

Background: Previous studies showed that insulin resistance and reduced muscle strength are risk factors for silent lacunar infarcts, but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on silent lacunar infarcts is completely unknown.Methods: We evaluated silent lacunar infarcts, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM (an index for insulin sensitivity), and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Results: Among the study subjects, 251 (16.4%) had silent lacunar infarcts. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI): 0.94-2.48], Low; 1.86 [95%CI: 1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [95%CI: 0.98-2.02], Low; 1.49 [95%CI: 1.04-2.15], p for trend 0.037) were independently associated with increased risk for silent lacunar infarcts in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95%CI: 1.64-11.45) more likely to have a silent lacunar infarct than those classified as having the highest insulin sensitivity and highest strength.Conclusions: Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of silent lacunar infarcts in elderly subjects, and their combination synergistically increased this risk.
A First-in-human Phase I Study of TAS0728, an Oral Covalent Binding Inhibitor of HER2, in Patients With Advanced Solid Tumors With HER2 or HER3 Aberrations.
Authors: Piha-Paul Sarina A , Azaro Analía , Arkenau Hendrik Tobias , Oh Do-Youn , Galsky Matthew D , Pal Sumanta Kumar , Hamada Kensuke , He Yaohua , Yamamiya Ikuo , Benhadji Karim , Hollebecque Antoine
Published: March 2021

TAS0728 is an oral covalent binding inhibitor of human epidermal growth factor receptor 2 (HER2). A first-in-human open-label, dose-escalation, phase I study (NCT03410927) was initiated to investigate the safety and dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of TAS0728 in adults with advanced solid tumors with HER2 or HER3 overexpression, amplification or mutation. In total, 19 patients received TAS0728 at escalating doses from 50 to 200 mg BID for 21-day cycles. Following escalation of the dose to 200 mg BID, a total of two DLTs were observed, both cases of Grade 3 diarrhea (lasting >48 hours and not responsive to aggressive antidiarrheal treatment). Following de-escalation of the dose to 150 mg BID, another DLT of Grade 3 diarrhea was observed in one patient. Additionally, at 150 mg BID, one patient had a fatal cardiac arrest after receiving 1 cycle (21 days) of TAS0728. The etiology of the cardiac arrest event was not clear, however causal relationship to TAS0728 could not be excluded due to the temporal association observed. Partial responses were observed in 2 of 14 patients evaluable for TAS0728 treatment response. The study was stopped due to unacceptable toxicity during the dose-escalation as the overall risk-benefit ratio no longer favored the dose level being tested, therefore the MTD was not determined. ClinicalTrials.gov registration number: NCT03410927; registered on January 25, 2018.
Underestimation of Luminal Eosinophilia by Quantitative Sputum Cytometry
Authors: Kjarsgaard Melanie , Adatia Adil , Bhalla Anurag , LaVigne Nicola , Radford Katherine , Huang Chynna , Mukherjee Manali , Nair Parameswaran
Published: March 2021

Rationale: On Wright-stained sputum cytospins, eosinophil differential of >1.2% is considered abnormal and ≥3% clinically relevant. We hypothesized that failure to consider free eosinophil granules (FEG), and the re-emergence of eosinophilia (at ≥1.2 and ≥2.3%) underestimate the prevalence of the eosinophilic phenotype.Methods: This is a retrospective analysis of our Institutional Review Board-approved clinical sputum database. Of the 24,176 examinations, 17,693 had viable cell counts from 9570 patients (6604 on one occasion, 2967 with two or more) with various airway diseases. In all samples, FEGs were semi-quantified to estimate the prevalence of eosinophilia at <1.2 and <2.3%. In those patients with sputum examined on more than one occasion, subsequent results identified re-emergence of eosinophilia at ³1.2 and ³2.3%.Results: Of those with intact cell counts (n=15,278), 8562 (56.0%) and 9690 (63.4%) would have been classified as clinically non-relevant eosinophilia of <1.2% and <2.3% respectively. Among those with two or more intact cell counts, 1142 (38.5%) and 1083 (36.5%) of samples had re-emergence of eosinophilia (at 1.2 and 2.3%), either when a previous neutrophilia resolved (n= 218/19.1%, n=312/28.8%) or due to a reduction in the dose of corticosteroids (n=634/21.4%, n=666/22.4%) with no significant differences between groups (p=0.018). There was a significant difference between the proportions of eosinophilic versus non-eosinophilic at 1.2 and 2.3%, using the presence of FEG and the non-intact cell count (p<0.001).Conclusions: A total of 3180 (32.8%) samples identified as non-eosinophilic, had clinically relevant airway eosinophilia that would not have been identified if the phenotypic classification was limited to ≥2.3% intact eosinophils on one occasion. This underestimation is likely to be significantly more if other means of airway eosinophilic activity were included and if mast cell activity and lymphocyte numbers, (not routinely quantified by sputum cytometry), could be contributing to the under-appreciation of airway T2 inflammatory processes.
An investigation on discharge servo parameters and machining servo mode optimization of MS-WEDM
Authors: Ma Huliang , Wang Yanqing , Lv Ming , Yang Shengqiang
Published: March 2021

Increasing the machining efficiency of middle speed wire electrical discharge machining (MS-WEDM) is usually through optimizing process parameters, but the discharge servo parameters of the servo controller can also be optimized to achieve the same purpose. This paper develops a multi-mode servo controller for MS-WEDM to investigate discharge servo parameters. Firstly, the structure and control principle of the servo controller are introduced, and the core functions are described in detail. Secondly, it introduces the discharge servo parameters that can be optimized: gap state threshold and feedback period. At the same time, the platform specifications and parameters for optimization experiments are introduced. Thirdly, the experimental scheme and result analysis of parameter optimization are described, and the optimized parameters are obtained. Finally, different machining experiments are carried out for the multi-mode of the servo controller to investigate the effectiveness and practicability of the different machining servo modes. In the parameter optimization and machining experiments, the recording function of the servo controller was used to draw the speed curve, and the servo response effects of different servo modes was obtained.
Influence of Mercury Exposure During Pregnancy to Neurodevelopmental Disorder: A Systematic Review Protocol
Authors: Nasruddin Nhelvy Kumala , Amqam Hasnawati , Wirayuda Agus Bintara Wirayuda , Natsir Muh. Fajaruddin , Syamsuar Syamsuar
Published: March 2021

Background: The general population might expose to Hg through various pathways. Prenatal or postnatal exposure to mercury might affect the fetus's neurodevelopment and then further affect the growth and development of the children. There are many reports on mercury exposure, but systematic reviews to conclude the result are still limited, particularly concerning pregnancy. Previous studies focus on one exposure path to Hg and biomarker. The objective is to systematically summarize the relevant records from systematic studies on the relationship between the exposure pattern during pregnancy to pregnant women's Hg concentration and neurodevelopmental disorder that occurred in the children.Method: We will search online databases (Google Schoolar, PUBMED, Sciencedirect, Proquest, Web of Science, Springerlink, DOAJ (Directory of Open Access Journals) and EBSCO MEDLINE) and reference lists of included articles. Two reviewers will independently screen the titles and abstracts and select the research involving pregnant women with mercury exposure and neurodevelopmental disorder fetus or children. These reviewers will also independently extract and manage the obtained data using a data extraction form that will cover information on characteristic, exposure, and outcomes. Meta-analysis will also be applied when homogeneous group of studies found.Discussion: This study will describe the available epidemiological evidence and summarise prevalence and incidence rates of mercury exposure and neurodevelopmental disorder. Mean difference of mercury level will be also presented. A better understanding of the relationship between mercury exposure and any neurodevelopmental disorder form will be helpful in the development of guidelines for mercury exposure management.Systematic review registration: It has been submitted to PROSPERO on February, 10th 2021.
Prevalence of intestinal parasitic infection and its associated factors among children in Puducherry, South India: A community-based study
Authors: Jeyaram Suganya , Saya Ganesh Kumar , Rajkumari Nonika , Ulaganeethi Revathi , Roy Pritam Kumar , Mathavaswamy Vijayageetha
Published: March 2021

There is paucity of studies at community level on prevalence of intestinal parasitic infection among under eighteen years age group. This cross-sectional community-based research aimed to determine the prevalence of intestinal worm infections and its associated risk factors among 1 to 18 years age group in Puducherry, India. Sociodemographic, behavioral and other associated factors were collected using a structured questionnaire. One stool sample was collected from each participant and examined using direct (saline/iodine wet mount) and concentration (floatation/sedimentation) microscopic techniques. Log binomial regression analysis was used to find the factors independently associated with intestinal parasitic infection. Of 187 participants who provided the stool sample, 25 (13.4%) had at least one of the parasitic infections and among them 12 (6.4%) had Soil Transmitted Helminth infection (STH) and 13 (6.9%) had intestinal protozoan parasites. Parasitic infection is marginally higher among 1 to 7 years age group (14.4%) compared to 8 to 18 years age group (12.1%). After adjusting for confounding, urban residence (APR = 3.3, 95% CI: 1.4-8.0) and open-air defecation (APR = 3.3, 95 % CI 1.4–7.5) were significantly associated with intestinal parasitic infections. One out of eight children had any of the parasitic infection and nearly 50% of parasitic infections were caused by STH. Those children residing in urban areas and practice of open-air defecation had higher prevalence of parasitic infection.
Effect of Prophylactic Ligation of the Thoracic Duct on Long-Term Survival in Patients Undergoing Esophagectomy: A Meta-Analysis
Authors: kun Mei , Chao Ce , Xuanren Long , Chao Ma , Rui Zhou , Bin Wang , Dongmei DI
Published: March 2021

Objective: To evaluate the existing literature by comparing long-term survival between patients who underwent prophylactic thoracic duct ligation (PLG) and non-prophylactic thoracic duct ligation (NPLG) during esophagectomy for esophageal cancer, a meta-analysis of relevant studies was conducted.Background: The effect of PLG and NPLG on the long-term survival in patients undergoing esophagectomy for treatment of esophageal cancer has not been established.Methods: All articles searches were performed in PubMed, Cochrane, Embase, and Web of Science, and the deadline is August 31, 2020. The search terms included esophagectomy AND thoracic duct. The selected articles compared the long-term survival of patients undergoing esophagectomy to treat esophageal cancer with prophylactic thoracic duct ligation (PLG) and non-prophylactic thoracic duct ligation (NPLG). The I2 test and X2 test were used to determine statistical heterogeneity. Publication bias was assessed using the Egger test. The results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). All data analysis was performed using Stata12.0 software.Result: A total of 4418 patients from eight studies were included in this meta-analysis. Pooled analysis revealed that a high overall survival (OS) was significantly associated with NPLG (HR=0.81, 95% CI: 0.74-0.88, P<.001), while the recurrence- free survival (RFS) and disease-free survival (DFS) were not significantly different (HR=1.02, 95% CI: 0.71-1.45, P<.001). There was no statistical difference in long-term survival among patients with different stages of esophageal cancer, while patients who underwent esophagectomy after 2019 had a better long-term prognosis (HR=0.57, 95% CI: 0.57-0.79). In addition, there was no significant difference in prognosis and survival between patients in Japan and China based on regional analysis.Conclusions: Our meta-analysis showed that NPLG was associated with better long-term survival. Thus, we should preserve the thoracic duct during esophageal cancer surgery.
IDH1R132H Mutation Inhibits the Proliferation and Glycolysis of Glioma Cells by Regulating the HIF-1α/LDHA Pathway
Authors: Li Hailong , Wang Shuwei , Wang Yonggang
Published: March 2021

Background: This study aims to explore the role and underlying mechanism of the IDH1R132H in the growth, migration, and glycolysis of glioma cells.Methods: The alternation of IDH1, HIF-1α, and LDHA genes in 283 LGG sample (TCGA LGG database) was analyzed on cBioportal. The expression of these three genes in glioma tissues with IDH1R132H mutation or IDH1 wild type (IDH1-WT) and normal brain tissues was also assessed using immunohistochemistry assay. In addition, U521 glioma cells were transfected with IDH1-WT or IDH1R132H to explore the role of IDH1 in the proliferation and migration of glioma cells in vitro. Cell growth curve, Transwell mitigation assay, and assessment of glucose consumption and lactate production were conducted to evaluate the proliferation, migration, and glycolysis of glioma cells.Results: The expression of HIF-1α and LDHA in IDH1R132H mutant was significantly lower than that in glioma cells with wild type IDH1 (P<0.05). IDH1R132H inhibited the proliferation and glycolysis of U521 glioma cells.Conclusion: The IDH1 mutation IDH1R132H plays an important role in the occurrence and development of glioma through inhibiting the expression of HIF-1α and glycolysis.
A Preliminary Study of Constructing Tissue Engineered Oral Mucosa
Authors: Zhang Qin , Tian Yu-Jing , Ding Tao , Femg De-Hong
Published: March 2021

Background: Adipose derived stem cells (ADSCs) have a great potential for tissue-engineering purposes, and they may be introduced in oral mucosa tissue engineering for urethroplasty. This study was aim to develop a tissue-engineered oral mucosa through seeding oral keratinocytes (OKs) and adipose derived stem cells (ADSCs) on small intestine submucosa (SIS). Methods: SIS was obtained from porcine small intestine, and OKs and ADSCs were obtained from canine sources and were cultured and expanded in vitro. The two cell lines were seeded on the two surfaces of the SIS, and the cell-scaffold compound graft was cultured in an air fluid level for 1 week.Results: The SIS exhibited a porous membrane, and no cells were found through HE staining. The model cultured with OK-SIS only formed a thin and loose epithelium. Whereas the model cultured with OK-SIS-ADSC was much thicker and denser. Conclusion: The co-cultured of ADSC and OK grew well on the SIS in which the OKs formed a multilayer of epithelium. So it is feasible to construct a tissue-engineered oral mucosa graft with ADSCs, OKs and SIS. The ADSCs contribute to a thicker epithelium formation.
Treatment of Posterolateral Tibial Plateau Fractures With a Rotational Support Plate and Special Pressurizer: a Technical Note and 12 Cases 
Authors: Chen Yu-Feng , Ren Dong , Geng Lin-Dan , Yao Shuang-Quan , Song Zhao-Hui , Guang Liang , Wang Tian-Ci , Wang Peng-Cheng
Published: March 2021

Background: Posterolateral tibial plateau fractures are uncommon fractures and challenging to treat. Although there are many surgical approaches and fixation methods for the treatment of these fractures, all of these methods have limitations. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes.Methods: From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analysed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score was used to evaluate knee function at the last follow-up.Results: The average follow-up time of all patients was 16.5 months (range, 12-25 months). The average bony union time was 3.2 months (range, 3-4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107°-145°). The average HSS score was 91 (range, 64-98). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period.Conclusions: With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.