bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Lupus Erythematosus Activity and Hydroxychloroquine Use Before and After End Stage Renal Disease
Authors: Guerrero Maria Salgado , Jimenez Alejandra Londono , Dobrowolski Chrisanna , Mowrey Wenzhu B. , Goilav Beatrice , Wang Shudan , Broder Anna
Published: August 2020

Background: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been studied. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. Methods: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development. Results: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission.Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD and 10/17(59%) patients with no manifestations of active disease post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p=0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p=0.005), CNS manifestations (6 [20%] vs 1 [4%], p=0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p=0.029).Conclusions: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized post-ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.
Improved Oncologic Outcomes Following Laparoscopic Surgery for Small T4 Colon Cancer : A Multi-center Comparative Study
Authors: Park Sung Sil , Lee Joon Sang , Park Hyoung-Chul , Park Sung Chan , Sohn Dae Kyung , Oh Jae Hwan , Han Kyung Su , Lee Dong-Won , Kang Sung-Bum , Park Kyu Joo , Jeong Seung‑Yong
Published: August 2020

Background: Laparoscopic surgery for T4 colon cancer may be safe in selected patients. Based on the theory that small tumor size might preoperatively predict a good laparoscopic surgery outcome, we herein compare the clinicopathologic and oncologic outcomes of open and laparoscopic surgery in small T4 colon cancer.Methods: In a retrospective multicenter study, we reviewed the data of 449 patients, including 117 patients with tumors ≤4 cm, who underwent T4 colon cancer surgery between January 2014 and December 2017. We compared the clinicopathologic and 3-year oncologic outcomes between the laparoscopic and open surgery groups.Results: Blood loss, length of hospital stay, and postoperative morbidity were lower in the laparoscopic group than in the open group (86 mL vs. 278 mL, p < 0.001; 10.0 days vs. 12.5 days, p = 0.003; and 18.0% vs. 29.5%, p = 0.005, respectively). There were no intergroup differences in overall survival (OS) and 3-year disease-free survival (DFS; 87.8% vs. 83.2%, p = 0.117; 69.5% vs. 68.1%, p = 0.408, respectively). Among patients with tumors of size ≤4 cm, blood loss was lower in the laparoscopic surgery group than in the open group (80 mL vs. 208 mL, p = 0.001); despite no statistical difference observed in the 3-year OS (84.4% vs 78.7%, p = 0.442), the laparoscopic group had a better 3-year DFS (73.8% vs. 46.0%, p = 0.004).Conclusions: Laparoscopic surgery showed similar outcomes to open surgery in T4 colon cancer patients, and may have favorable short-term oncologic outcomes in patients with small T4 tumors.
Evaluation and improvement of emergency capacity of medical staff for the COVID-19: A cross-sectional study in China
Authors: Hu Shu-Xiao , Chen Chang-Fu , Liu Qing , Zhang Gao-Fei , Cheng Hua-Lin , Zhang Yan-Xin
Published: August 2020

Background: The coronavirus disease 2019 (COVID-19) has spread to 215 countries around the world. In the studies of responding to public health emergencies, most of them are focused on health systems, local governments or medical organizations, but less on individuals. Medical staff, however, are the core strength for responding to public health emergencies. The aims of this study are to investigate the status of medical staff’s emergency capacity during the Pandemic and to provide intellectual support for further enhancing the medical staff's ability to ensure the smooth operation of medical rescue. Methods: This study conducted a cross-sectional survey of four hospitals, which were designated to treat patients with COVID-19 in China. Based on the emergency capacity system for infectious diseases of medical staff, an improved Emergency Preparedness Information Questionnaire was used to evaluate the emergency capacity of medical staff. Linear regression and one-way analysis of variance were used to test the difference in the emergency capacity of medical staff; Spearman correlation analysis was used to study the correlation between self-efficacy and emergency capacity of medical staff. Results: The overall emergency capacity of the surveyed medical staff was at a medium level. There was a correlation between emergency capacity and age, working years, position, educational background and area where medical staff work. Emergency capacity was not related to the hospital grades. Emergency capacity was significantly related to whether medical staff had participated in frontline Pandemic prevention work. There was also a positive correlation between emergency capacity and self-efficacy of medical staff. Conclusions: The results highlighted the importance of the training mechanism for emergency personnel. The emergency input for public health emergencies should be increased to improve the emergency capacity of medical staff. In addition, it is necessary to pay attention to the mental health of medical staff.
Clinical pharmacist interventions in managing Key Monitoring Drugs in China
Authors: Yang Jing , Zheng Lei , Guan Yuyao , Zhang Xiaoli , Song Chao , Gu Yuchao
Published: August 2020

Background Drug-related problems (DRPs) are common in hospitalized patients using Key Monitoring Drugs. Clinical pharmacy services could minimize drug-related harm and improve patient care.Objective The aim of this study was to standardize the clinical application of Key Monitoring Drugs, reduce the Drug-related problems (DRPs) and drug costs by clinical pharmacist interventions.Methods Clinical pharmacist formulate management measures for Key Monitoring Drugs using evidence-based medicine and analyze the DRPs of Key Monitoring Drugs over a period of 5 years from 2015 to 2019. The drug cost and DRPs of Key Monitoring Drugs within five years after interventions by clinical pharmacist.Results In 2019, the total cost of the use of Key Monitoring Drugs decreased by 10.12 million CNY, in comparison to that in 2015. The proportion of revenue from Key Monitoring Drugs decreased by 11.49% from 2015 to 2019. The per capita drug cost of Key Monitoring Drugs gradually decreased, this resulted in a saving of 580.07 CNY from 2015 to 2019. The DRPs of Key Monitoring Drugs decreased by 45.50% from 2015 to 2019. Through administrative intervention, prescription review, information management, and pharmaco-economicevaluation, a scientific management system of Key Monitoring Drugs has been established, which can standardize the use of Key Monitoring Drugs and reduce their cost. Conclusion Clinical pharmacists’ interventions assisted in early detection Drug-related problems of Key Monitoring Drugs and prevention of the consequent patient harms.
Ultrafast imaging of spontaneous symmetry breaking in a photoionized molecular system
Authors: Li Min , Zhang Ming , Vendrell Oriol , Guo Zhenning , Zhu Qianru , Gao Xiang , Cao Lushuai , Guo Keyu , Su Qinqin , Cao Wei , Luo Siqiang , Yan Jiaqing , Zhou Yueming , Liu Yunquan , Lu Peixiang , Li Zheng
Published: August 2020

The Jahn-Teller effect is an essential mechanism of spontaneous symmetry breaking in molecular and solid state systems, and has far-reaching consequences in many fields. Up to now, to direct image the onset of Jahn-Teller symmetry breaking remains unreached. Employing ultrafast ion-coincidence Coulomb explosion imaging with sub-10 fs resolution, we unambiguously imaged the ultrafast dynamics of Jahn-Teller deformations of CH4+ cation in real space. It is unraveled that the Jahn-Teller deformation from C3v to C2v geometries takes a characteristic time of about 20 femtoseconds for this system. Classical and quantum molecular dynamics simulations agree well with the measurement, and reveal dynamics for the build-up of the C2v structure involving complex phasing process of multiple vibrational pathways of the CH4+ cation.
Gait Analysis of Healthy Rhesus Monkeys Using a Pressure-sensing Walkway System
Authors: Won Jinyoung , Kim Keonwoo , Yeo Hyeon-Gu , Park Junghyung , Seo Jincheol , Kim Yu Gyeong , Park Sung-Hyun , Choi Won Seok , Jeon Chang-Yeop , Lim Kyung Seob , Jeong Jinwoo , Choi Ji-Woong , Lee Youngjeon
Published: August 2020

Background: Gait analysis in non-human primate models has been performed to elucidate the neural systems involved in controlling quadrupedal locomotor behavior. This study aimed to use a pressure-sensing walkway to identify characteristics of species-specific quadrupedal locomotion in rhesus monkeys. A total of nine healthy adult female rhesus monkeys (Macaca mulatta) were used for gait analysis. We measured the temporo-spatial and kinetic parameters of quadrupedal gait using a custom-built pressure-sensing walkway and compared the left- and right-side parameters to assess the symmetry of the gait pattern. Results: All temporo-spatial and kinetic parameter values showed no significant differences among the nine rhesus monkeys for both the forelimbs and hindlimbs. However, significant differences were observed between forelimb and hindlimb kinetic parameters such as peak vertical force, vertical impulse, and the percentage of body weight distribution. All kinetic parameter values were higher for the forelimbs than for the hindlimbs. These data indicated that the center of gravity in healthy rhesus monkeys is located at the forelimbs rather than at the hindlimbs while walking. Furthermore, the symmetry indices considered for symmetric gait pattern showed a low variability. Most median symmetry index values were nearly zero, indicating no difference between the right and left sides. Conclusions: This study described valid methods for assessing gait parameters and demonstrated rhesus-specific characteristics of quadrupedal locomotion, providing a basis for the assessment of gait normality in rhesus monkeys.
Location Inference for Hidden Population with Online Text Analysis
Authors: Chuchu Liu , Ziqiang Cao , Xin Lu
Published: August 2020

Understanding the demographics of hidden population, such as men who have sex with men (MSM), sex workers, or injecting drug users, are of great importance for the adequately deployment of intervention strategies and public health decision making. However, due to the hard-to-access properties, e.g., lack of a sampling frame, sensitivity issue, reporting error, etc., traditional survey methods are largely limited when studying such populations. With data extracted from the very active online community of MSM in China, in this study we adopt and develop location inferring methods to achieve a high-resolution mapping of users in this community at national level. The performances of popular inference algorithms are compared to elucidate the most suitable approach. In addition, we propose a new hybrid model, which is proven to achieve the highest accuracy for inferring locations of online users only based on text content. This method is conducive to overcoming the sparse location labeling problem in user profiles, and can be extended to the inference of geo-statistics for other hidden populations.
Small molecule inhibitor of OGG1 blocks oxidative DNA damage repair at telomeres and potentiates Methotrexate anticancer effects
Authors: Baquero Juan Miguel , Benítez-Buelga Carlos , Rajagopal Varshni , Zhenjun Zhao , Torres-Ruiz Raúl , Mueller Sarah , Hanna Bishoy Magdi Fekry , Loseva Olga , Wallner Olov , Michel Maurice , Rodríguez-Perales Sandra , Gad Helge , Visnes Torkild , Helleday Thomas , Benítez Javier , Osorio Ana
Published: August 2020

Background: The most common oxidative DNA lesion is 8-oxoguanine (8-oxoG) which is mainly recognized and excised by the glycosylase OGG1, initiating the Base Excision Repair (BER) pathway. Telomeres are particularly sensitive to oxidative stress which disrupts telomere homeostasis triggering genome instability. Methods: We used U2OS OGG1-GFP osteosarcoma cell line to study the role of OGG1 at the telomeres in response to oxidative stress. Next, we investigated the effects of inactivating pharmacologically the BER during oxidative stress (OS) conditions by using a specific small molecule inhibitor of OGG1 (TH5487) in different human cell lines. Results: We have found that during OS, TH5487 effectively blocks BER initiation at telomeres causing accumulation of oxidized bases at this region, correlating with other phenotypes such as telomere losses, micronuclei formation and mild proliferation defects. Besides, the antimetabolite Methotrexate synergizes with TH5487 through induction of intracellular ROS formation, which potentiates TH5487 mediated telomere and genome instability in different cell lines. Conclusions: Our findings demonstrate that OGG1 is required to protect telomeres from OS and present OGG1 inhibitors as a tool to induce oxidative DNA damage at telomeres, with the potential for developing new combination therapies for cancer treatment.
Allelic diversity of merozoite surface protein-1 (MSP 1) and MSP 2 genes, and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia
Authors: Jamil Kurnia Fitri , Pratama Nandha Rizki , Marantina Sylvia Sance , Harapan Harapan , Kurniawan Muhammad Riza , Zanaria Tjut Mariam , Hutagalung Jontari , Rozi Ismail E , Asih Puji BS , Supargiyono Supargiyono , Syafruddin Din
Published: August 2020

Background
Malaria control programme in Indonesia has successfully brought down malaria incidence in many parts of the country, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein genes among the P. falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation.
Methods
Screening of over 500 malaria cases admitted to the 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and Polymerase Chain Reaction (PCR) amplified for the MSP1 and MSP2 allelic subfamilies.
Results
Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases classified as severe and 71 as mild malaria. Analysis of MSP 1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of MSP 2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects (carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp2 alleles is slightly higher than MSP 1 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and MSP 1 and MSP 2 alleles revealed that liver function abnormal value was associated with the MSP 2 mixed alleles (p < 0.05; odds ratio = 0.13; CI95%= 0.03–0.53). Malaria severity was associated with the mixed MSP 1 of K1 + RO33 with severe malaria (p < 0.05; odds ratio = 28.50; CI 95%= 1.59-1532.3).
Conclusion
This study found a strong association between severe malaria in Aceh with subjects carrying the MSP 1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the MSP 2 mixed allelic subfamilies. Further study in different geographic areas is recommended.
Local low-rank approach to nonlinear-matrix completion
Authors: Sasaki Ryohei , Konishi Katsumi , Takahashi Tomohiro , Furukawa Toshihiro
Published: August 2020

This paper deals with a problem of matrix completion in which each column vector of the matrix belongs to a low-dimensional differentiable manifold (LDDM), with the target matrix being high or full rank. To solve this problem, algorithms based on polynomial mapping and matrix-rank minimization (MRM) have been proposed; such methods assume that each column vector of the target matrix is generated as a vector in a low-dimensional linear subspace (LDLS) and mapped to a p-th order polynomial, and that the rank of a matrix whose column vectors are d-th monomial features of target column vectors is deficient. However, a large number of columns and observed values are needed to strictly solve the MRM problem using this method when p is large; therefore, this paper proposes a new method for obtaining the solution by minimizing the rank of the submatrix without transforming the target matrix, so as to obtain high estimation accuracy even when the number of columns is small. This method is based on the assumption that an LDDM can be approximated locally as an LDLS to achieve high completion accuracy without transforming the target matrix. Numerical examples show that the proposed method has a higher accuracy than other low-rank approaches.
The interaction of water with archeological birch bark and its effects on swelling, shrinking and deformations
Authors: Klügl Johanna , Pietro Giovanna Di
Published: August 2020

In this paper we present results of water sorption of archaeological, ethnographical and contemporary birch bark and of the water-induced size and shape changes during humidification and drying. The analysis revealed that the equilibrium moisture content is higher if lenticels or inner bark are present and that the burial context influences the sorption behavior: the better the preservation condition of the archaeological birch bark, the lower the equilibrium moisture content. Compared to other organic materials like wood, the water uptake and the related swelling of outer birch bark is modest. This can be attributed to the cell structure and composition: outer birch bark is composed of closed cells made to a large extent of hydrophobic components (suberin, lignin). We show that warping of the bark takes place at high moisture content. This deformation is related to the plasticization effect of water and to the release of the built-in tension related to the stretching of the cells during the tree’s growth. Our results provide a first guidance to conservators in the decision of water treatments on birch bark objects.
Association Between Intimate Partner Violence During Pregnancy And Birth Asphyxia In Hospitals Of Tigray Region, Ethiopia
Authors: Gebreslasie Kahsay , Gebre Gelawdiwos , Zenebe Dawit , Weldemariam Solomon , Mehari Mehret Ab , Nardos Rahel , Birhanne Akilil
Published: August 2020

Background: Birth asphyxia is the main causes of neonatal mortality and morbidity worldwide. Some studies indicate intimate partner violence during pregnancy is a risk factor for birth asphyxia. In Ethiopia, intimate partner violence is reported in nearly 26 percent of pregnancies. Despite this high prevalence, there is lack of data about the association of birth asphyxia and intimate partner violence. The aim of this study was to assess the prevalence of intimate partner violence during pregnancy and its associated factors with birth asphyxia in health facilities in the Tigray region of northern Ethiopia. Methods: This was an institutional based cross-sectional study conducted at select health facilities in the Tigray region of Ethiopia. Random sampling technique was employed to select health facilities and systematic sampling was used to select the study participants. Data was entered by using Epi info version 3.5.1 and was analyzed using SPSS version 20. Bivariate and multivariate analysis was done to assess the association between exposure to intimate partner violence during pregnancy and birth asphyxia after adjusting for possible confounders. Results: The prevalence of intimate partner violence during pregnancy was 7.3%. Eighty two (12.7%) babies were delivered with birth asphyxia. Intimate partner violence during pregnancy had significant association with birth asphyxia AOR (95% CI) =4.4(2-9.8). In addition to this residence, AOR (95% CI) =2.7(1.55-4.8), age>19,AOR (95% CI) =2.9(1.29-6.5), age 20-35, AOR (95% CI) =3.1(1.06-9.3), gestational age<37 weeks, AOR(95% CI)=7.2(3.5-14.8) and low birth weight, AOR(95% CI)=3.9(2.1-7.3) had significant association with birth asphyxia.Conclusions: The prevalence of birth asphyxia in this study is high. Women who experienced intimate partner violence during pregnancy increased the risk of birth asphyxia.
The Effect of Vertebral Venous Collaterals on Intracranial Hypertension and Related Symptoms in Patients with Bilateral Transverse Sinus Stenosis
Authors: Li Min , Bai Chaobo , Sun Jingkun , Xia Ning , Meng Ran , Ji Xunming
Published: August 2020

Background: Vertebral venous collaterals (VVC) were often found in patients with bilateral transverse sinus stenosis (BTSS). The purpose of this study was to investigate the physiological role of VVC in BTSS patients.Methods: The index of TSS was used in the assessment of BTSS severity. Subjects underwent a standard lumbar puncture to measure the intracranial pressure (ICP). Papilledema and tinnitus were evaluated by using Frisén's grade and questionnaires for tinnitus handicap inventory (THI), respectively. The intensity and impact of headache was assessed by using 10-point Numeric Pain Rating Scale (NPRS) and six-item Headache Impact Test (HIT-6).Results: BTSS group had more patients with severe intracranial hypertension (IH) and less patients with normal ICP. BTSS patients had higher ICP than normal controls. Further analysis on VVC showed that VVC decreased the elevated ICP in BTSS patients and exerted no impact on ICP in normal controls. A similar incidence of VVC in BTSS patients and normal controls were found. BTSS patients with normal ICP and mild IH exhibited a higher incidence of VVC compared with those with severe IH. VVC, rather than the severity of BTSS, regulated the ICP. Furthermore, VVC alleviated IH-related clinical manifestations including papilledema and tinnitus in BTSS patients.Conclusions: The present study demonstrated BTSS is correlated with IH. The presence of VVC, which is postulated to be congenitally formed, normalizes the elevated ICP and alleviated IH-related symptoms in BTSS patients. VVC may be used as an indicator of relatively low ICP in BTSS patients.Trial registration: This study was registered retrospectively on 07/28/2020 (NCT04492332).
Morita-Baylis-Hillman Reaction Inspired [3,3]-Rearrangement of Aryl Iodanes with α,β-Unsaturated Oxazolines
Authors: Zhang Lei , Bao Wangzhen , Liang Yuchen , Pan Wenjing , Li Dongyang , Kong Lichun , Wang Zhi-Xiang , Peng Bo
Published: August 2020

The [3,3]-rearrangement of aryl iodanes with α,β-unsaturated oxazolines has been developed by merging Morita-Baylis-Hillman (MBH) process into the rearrangement reaction. The method allows for the exclusively E-selective synthesis of a wide variety of valuable α-aryl α,β-unsaturated oxazolines which can be difficult to synthesize with other known methods. Experimental and computational mechanistic studies unraveled that the reaction proceeds via the assembly of both coupling partners followed by MBH-type addition to form rearrangement precursor, [3,3]-rearrangement, and stepwise E1cb-elimination. The E-selectivity of the reaction is favored both kinetically and thermodynamically.
Cohort profile: Why do people keep hurting their back?
Authors: Klyne David Murray , Hoorn Wolbert van den , Barbe Mary Frances , Cholewicki Jacek , Hall Leanne , Khan Asad , Meroni Roberto , Moseley G. Lorimer , Nicholas Michael , O'Sullivan Lee , Park Rachel , Russell Glen , Sterling Michele , Hodges Paul William
Published: August 2020

Objective Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many individuals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to; (1) evaluate whether promising and potentially modifiable biological, psychological, social and behavioural factors, along with their possible interactions, predict LBP outcome after an acute episode; (2) compare these factors between individuals with and without acute LBP; and (3) evaluate the time-course of changes in these factors from LBP onset. This paper outlines the methodology and compares baseline characteristics between acute LBP and control, and LBP participants with and without follow-up.Results 133 individuals with acute LBP and 74 pain-free individuals participated. Bio-psycho-social and behavioural measures were collected at baseline and 3-monthly for 12 months (LBP) or 3 months (control). Pain and disability were recorded fortnightly. Baseline characteristics were mostly similar between those who did and did not return for follow-up. Initial analyses of this cohort have revealed important insights into the pathways involved in acute-to-chronic LBP. These and future findings will provide new targets for treatment and prevention of persistent and recurrent LBP.
Local Efficacy of Corticosteroids as an Adjuvant for Periarticular Cocktail Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Double-blind Controlled Trial
Authors: peng huiming , wang wei , lin jin , weng xisheng , qian wenwei , wang wenda
Published: August 2020

Background: Multimodal cocktail periarticular injection(MCPI) including corticosteroids is currently widely applied to reduce postoperative pain and swelling following total knee arthroplasty (TKA). However the addition of steroids is controversial.This prospective, double-blinded, randomized, controlled trial compares the safety and efficacy of MCPI with or without corticosteroids.Methods: A total of 60 patients (120 knees) who underwent simultaneous bilateral TKAs received periarticular injections with added betamethasone (7mg) in a randomly selected knee, and the other knee was injected without added corticosteroids. The visual analog scale(VAS) pain scores at rest and in motion, range of motion (ROM), thigh swelling, hospital for special surgery(HSS) score, and adverse events were compared between the 2 knees.Results: There were no statistically significant differences in the visual analog scale score, ROM, thigh girth, HSS score, and complications between the 2 kness. The patients were unable to detect a difference in the functional recovery between their knees on postoperative day 3or at the 3 month follow-up.Conclusion: Betamethasone injections are ineffective locally for relieving pain, reducing swelling, and improving the postoperative ROM.Trial registration: Chinese Clinical Trial RegistryNumber: ChiCTR-OPC-17013503, Date of Registration: 2017-11-23 URL:http://www.chictr.org.cn/showproj.aspx?proj=23146
Conformation and Dynamics of the Kinase Domain Drive Subcellular Location and Activation of LRRK2.
Authors: Schmidt Sven H. , Weng Jui-Hung , Aoto Phillip C. , Boassa Daniela , Silletti Steven , Mathea Sebastian , Hu Junru , Wallbott Maximilian , Komives Elizabeth A. , Knapp Stefan , Herberg Friedrich W. , Taylor Susan S.
Published: August 2020

Background: Leucine-Rich Repeat Kinase 2 (LRRK2) is a complex multi-domain protein where LRRK2-mutations are associated with Parkinson´s Disease (PD). To explore how pathogenic PD-mutations hijack the finely tuned activation process of LRRK2, we here used a multi-tiered approach. Methods: First, the spatial and temporal distribution of full-length LRRK2 was investigated by a real-time cell-based assay in the presence and absence of LRRK2-kinase inhibitors. In a 2nd layer we explored the consequences of PD mutations as well as removal of the N-terminal domains employing a construct containing the ROC, Cor, Kinase and WD40 domains (LRRK2RCKW). We focused on the biochemical characterization of LRRK2RCKW variants based on kinase assays using Rab8a or LRRKtide as substrates. Next, we used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to map the solvent accessible regions of LRRK2RCKW in the presence and absence of the LRRK2 inhibitor MLi-2. Finally, Molecular Dynamics simulations on the kinase domain were applied to elucidate differences in breathing dynamics between wild type and mutants of the DYGψ motif. Results: Our cellular approaches revealed that the kinase inhibitors MLi-2 and rebastinib both freeze the kinase domain in a stable conformation, however, only MLi-2 resembles an active conformation and induces filament formation. LRRK2RCKW showed, regardless of the mutation it was combined with, filament formation, indicating a shielding function of the N-terminal domains. This shielding function is impaired for pathogenic mutations in full length LRRK2. LRRK2RCKW retained kinase activity similar to full-length LRRK2. HDX-MS provided a comprehensive allosteric portrait of the kinase domain and revealed how MLi-2 binding is sensed by the entire protein. Molecular Dynamics simulations suggest that, while all domains contribute to regulating kinase activity and spatial distribution, it is the highly dynamic kinase domain, driven by the DYGψ motif, that coordinates the overall domain crosstalk and serves as a regulatory hub for the intrinsic regulation of LRRK2.Conclusion: These studies confirm our hypothesis that the N-terminal scaffolding domains shield the catalytic domains in an inactive state. PD mutations, MLi-2, or Rab GTPases can all unleash the catalytic domains while the active kinase conformation, but not kinase activity, is essential for docking onto microtubules.
Structural and biochemical mechanisms of NLRP1 inhibition by DPP9
Authors: Chai Jijie , Huang Menghang , Zhang Xiaoxiao , Ann Toh Gee , Gong Qin , Wang Jia , Han Zhifu , Wu Bin , Zhong Franklin
Published: August 2020

The nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires auto-cleavage within its FIIND domain1-7. In resting cells, the dipeptidyl peptidase DPP9 interacts with NLRP1-FIIND and together with a related enzyme DPP8, suppresses spontaneous NLRP1 activation8,9. The mechanisms of DPP8/9-mediated NLRP1 inhibition, however, remain elusive. Here we provide structural and biochemical evidence demonstrating that rat NLRP1 (rNLRP1) interacts with rDPP9 in a stepwise manner to form a 2:1 complex. An auto-inhibited rNLRP1 molecule first interacts with rDPP9 via its ZU5 domain. This 1:1 rNLRP1-rDPP9 complex then captures the UPA domain of a second rNLRP1 molecule via a UPA-interacting site on DPP9 and dimeric UPA-UPA interactions with the first rNLRP1. The 2:1 rNLRP1-rDPP9 complex prevents NLRP1 UPA-mediated higher order oligomerization and maintains NLRP1 in the auto-inhibited state. Structure-guided biochemical and functional assays show that both NLRP1-binding and its enzymatic activity are required for DPP9 to suppress NLRP1, supporting guard-type activation of the NLR. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on activation of the NLRP1 inflammasome.
Laser-stimulated fluorescence reveals unseen details in fossils from the Solnhofen Limestone (Upper Jurassic, Bavaria, Germany)
Authors: Barlow Luke , Pittman Michael , Martill David , Kaye Thomas , Butcher Anthony
Published: August 2020

Laser-Stimulated Fluorescence (LSF) has seen increased use in palaeontological investigations in recent years. The method uses the high flux of laser light to reveal details sometimes missed by ultraviolet (UV) and optical wavelengths. In this study, we compare the results of LSF with UV on a range of fossils from the Upper Jurassic Solnhofen Limestone Konservat-Lagerstätte of Bavaria, Germany. The methodology follows previous protocols with modifications made to enhance laser beam intensity. Our experiments show the value of LSF in revealing shallow subsurface detail of specimens, previously not widely applied to Solnhofen fossils. In particular, fossil decapods from the Solnhofen Limestone reveal full body outlines, even under the matrix, along with details of segmentation within the appendages such as limbs and antennae. The results indicate that LSF can be used on both vertebrate and invertebrate fossils and may surpass the information provided by traditional UV methods in some specimens.
Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-Human Primates
Authors: Fischer Tracy , Rutkai Ibolya , Mayer Meredith , Hellmers Linh , Ning Bo , Huang Zhen , Monjure Christopher , Coyne Carol , Silvestri Rachel , Golden Nadia , Hensley Krystle , Chandler Kristin , Lehmicke Gabrielle , Bix Geregory , Maness Nicholas , Russell-Lodrigue Kasi , Hu Tony , Roy Chad , Blair Robert , Bohm Rudolf , Doyle-Meyers Lara , Rappaport Jay
Published: August 2020

Neurological manifestations are a significant complication of coronavirus infection disease-19 (COVID-19). Understanding how COVID-19 contributes to neurological disease is needed for appropriate treatment of infected patients, as well as in initiating relevant follow-up care after recovery. Investigation of autopsied brain tissue has been key to advancing our understanding of the neuropathogenesis of a large number of infectious and non-infectious diseases affecting the central nervous system (CNS). Due to the highly infectious nature of the etiologic agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a paucity of tissues available for comprehensive investigation. Here, we show for the first time, microhemorrhages and neuropathology that is consistent with hypoxic injury in SARS-CoV-2 infected non-human primates (NHPs). Importantly, this was seen among infected animals that did not develop severe respiratory disease. This finding underscores the importance of vaccinating against SARS-CoV-2, even among populations that have a reduced risk for developing of severe disease, to prevent long-term or permanent neurological sequelae. Sparse virus was detected in brain endothelial cells but did not associate with the severity of CNS injury. We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.
Epidemiological profile of Plasmodium ovale spp. imported from Africa to Anhui Province, China, 2012 – 2019
Authors: Zhang Tao , Wang Shuqi , Wang Duoquan , Auburn Sarah , Lu Shenning , Xu Xian , Jiang Jingjing , Lyu Xiaofeng , Yu Chen , Tian Cuicui , Li Shizhu , Li Weidong
Published: August 2020

Background
Although autochthonous malaria cases are no longer reported in Anhui Province, China, imported malaria has become a major health concern. The proportion of reported malaria cases caused by Plasmodium ovale spp. increased to levels higher than expected during 2012 to 2019, and showed two peaks, 19.69% in 2015 and 19.35% in 2018.
Methods
We conducted a case-based retrospective study, using data collected from the China Information System for Disease Control and Prevention and Information System for Parasitic Disease Control and Prevention from 2012–2019, to describe the trends and differences between P. o. curtisi and P. o. wallikeri. Epidemiological characteristics were analyzed using descriptive statistics.
Results
P. ovale curtisi and P. ovale wallikeri were found simultaneously circulating in 14 African countries. Among 128 patients infected with P. ovale spp., the proportion of mixed infection cases was 10.16%. Six cases of co-infection by P. ovale and P. falciparum were observed, each presenting with two clinical attacks (the first attack was due to P. falciparum and the second was due to P. ovale spp.) at different intervals. Accurate identification of the infecting species was achieved in only 20.00% of cases with P. ovale infection. At the reporting units, 32.17% and 6.96% of P. ovale spp. cases were misdiagnosed as P. vivax and P. falciparum, respectively.
Conclusion
Our finding indicates that the ability of P. ovale spp. to co-infect with other malarial species has been previously underestimated and providing rational evidence for the existence of hypnozoites in P. ovale spp. P. o. curtisi and P. o. wallikeri circulate simultaneously in Africa, and the incidence of P. ovale spp. is probably also underestimated in these source countries where the disease is endemic. Given the low rate of species identification, more sensitive point-of-care detection methods need to be developed for P. ovale spp., and introduced in non-endemic areas.
Altered Circulating Free Oxysterols in Mild Cognitive Impairment: Relationship to Diet, Lipids and Genetics
Authors: An Yu , Yu Huiyan , Zhang Xiaona , Wang Yushan , Liu Wen , Wang Tao , Wang Lijing , Xiao Rong
Published: August 2020

BackgroundOxysterols, products of cholesterol oxidation, seem dysregulated in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, little is known about serum free oxysterol (biologically active form) profiles for MCI.MethodsSerum free oxysterol profiles were measured by ultra-performance liquid chromatography-mass spectrometry in discovery (n = 145) and validation batch (n = 356), both of which were constituted with cognitively normal individuals and MCI patients. We assessed associations of oxysterols with demographics, cognition, diet, lipids and genetics.Results27-Hydroxycholesterol and 7α-hydroxy-3-oxo-4-cholestenoic acid could distinguish MCI from control with good performance in both discovery batch (AUC = 0.80) and validation batch (AUC = 0.71). MCI status could affect correlation patterns among oxysterols, cognition and lipids. Genetic variants in APOE, CYP27A1, CYP46A1 showed inverse associations with cognition and lipids/oxysterol levels while CYP7A1 showed consistent associations.ConclusionsWe identify for the first time an altered free oxysterol profile and report associations with genetic variants in MCI using two-step case-control studies.Trial registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610
Measuring the International Structural Competitiveness and the Hierarchy of National Economies: The Case of the European Union
Authors: Markaki Maria Socrates , Economakis George
Published: August 2020

The determination of the level of competitiveness of national economies and the resulting hierarchy in the world economy is a central economic issue. Research on the subject has been mostly dominated by empirical, rather atheoretical, studies. In this paper, the determination of the international competitiveness level is achieved by using three criteria, which jointly define the level of international structural competitiveness: –the ratio of technologically advanced products in exports, the degree of economic diversification, and the level of the interconnectedness of the economy. The Technologically Advanced Domestic Valued Added in Exports condenses the above three criteria and it is proposed as a measure of international structural competitiveness. In addition, another measure of international structural competitiveness is being examined and tested: the Economic Complexity Index. The implementation of both measures in the European Union reveals similar results regarding the hierarchical position of the economies of the European Union member states, in terms of their international competitiveness.JEL classification: R15, C67, F15
O-vanillin Attenuated Toll-like Receptor 2 Induces Senescence in Intervertebral Disc Cells of Patients With Back Pain
Authors: Mannarino Matthew , Cherif Hosni , Li Li , Sheng Kai , Rabau Oded , Jarzem Peter , Weber Michael H. , Ouellet Jean A. , Haglund Lisbet
Published: August 2020

Backgroud: There are an increased level of senescent cells and Toll Like Receptor-1 -2 -4 and -6 (TLR) expression in degenerating IVDs from back pain patients. However, it is currently not known if the higher expression is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence.Methods: Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results: An increase in senescent cells was found following 48h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression and protein expression was found following 48h induction with TLR-2/6 agonist. Treatment with o-Vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-Vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression.Conclusions: Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and backpain and in cells from degenerating human IVD of patients with disc degeneration and backpain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP and TLR-2 expression suggest o-Vanillin as a potential disease modifying drug for patients with disc degeneration and backpain.
Research on PDMA communication system based on Complete Complementary Sequence
Authors: Li Shufeng , Su Baoxin , Jin Libiao
Published: August 2020

Pattern division multiple access (PDMA) is a new non-orthogonal multiple access (NOMA) technology. It is proposed to meet the challenge of 5G large-scale connectivity and high-frequency spectral efficiency. Compared with traditional orthogonal multiple access (OMA), PDMA can support more users through the allocation of non-orthogonal resources. Due to perfect aperiodic correlation, complete complementary sequences (CCS) still has research value in 5G. In order to apply the advantages of CCS to NOMA communication system, this paper proposes a system model of CCS spread spectrum coding based on PDMA. CCS is used as spread spectrum code to improve the performance of PDMA communication system. At the same time, on the basis of spread spectrum technology, this paper analyzes the average power allocation algorithm and water-filling power allocation algorithm, and a dynamic power allocation algorithm based on the transmission rate and practical application is proposed. The simulation results show that the system model can effectively improve the performance of the system.
Mechanism of Eucalyptus Volatile Oil Application for Preventing and Treating Pseudomonas Aeruginosa Infection in Vitro
Authors: Yang Lei , Huang Qing , Huang Xiaodong , Lin Zhimin , Gao Xingxin , Chen Songlin , Zhao Lili , Lin Yinghui , Hua Guangzong , Li Sheng
Published: August 2020

Background The mechanism of eucalyptus volatile oil application on the prevention and treatment of burn infections caused by Pseudomonas aeruginosa (PA) was need to examined.Methods The effect of eucalyptus volatile oil on bacterial biofilm was investigated using a PA biofilm model. The expression of LasI mRNA in PA was detected by RT-PCR. Results The minimum inhibitory concentration test showed that the volatile oil of Eucalyptus urophylla in 20% concentration or more could exert an antibacterial effect. However, neither high nor low concentration of the eucalyptus volatile oil had a zone of inhibition. In scanning electron microscopy, the volatile oil group exhibited a significant delay compared with the control group. The volatile oil group also had a significantly lower LasI mRNA expression than the control group. Conclusion As a Chinese medicine, the volatile oil of E. urophylla can affect PA proliferation and biofilm formation by interfering with the expression of LasI, thereby successfully preventing and treating burn infection caused by PA.
Outcome measures for assessing change over time in studies of symptomatic children with hypermobility: a systematic review
Authors: Maarj Muhammad , Coda Andrea , Tofts Louise , Williams Cylie , Santos Derek , Pacey Verity
Published: August 2020

Background This study aimed to synthesise outcome measure type and use in interventional or prospective longitudinal studies of children with generalised joint hypermobility (GJH) and associated symptoms. Method Electronic searches of Medline, CINAHL and Embase databases from inception to 16th March 2020 were performed for studies of children with GJH and symptoms between 5-18 years reporting repeated outcome measures collected at least 4 weeks apart. Methodological quality of eligible studies were described using the Downs and Black checklist.Results Six studies comprising of five interventional, and one prospective observational study (total of 388 children) met the inclusion criteria. Interventional study durations were between 2 to 3 months, with up to 10 months post-intervention follow-up, while the observational study spanned 3 years. Three main constructs of pain, function and quality of life were reported as primary outcome measures using 20 different instruments. All but one measure was validated in paediatric populations, but not specifically for children with GJH and symptoms. One study assessed fatigue, reporting disabling fatigue to be associated with higher pain intensity. Conclusions There were no agreed sets of outcome measures for children with GJH and symptoms found. The standardisation of assessment tools across paediatric clinical trials is needed. Four constructs of pain, function, quality of life and fatigue are recommended to be included with agreed upon, validated, objective tools