bluuebunny/crossref_metadata_2025 huggingface dataset:
Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis
Authors: Lee Mirae , Kim Seok-hyung , Jhee Jong Hyun , Kim Tae Yeon , Choi Hoon Young , Kim Hyung Jong , Park Hyeong Cheon
Published: July 2020

Background: Renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of chronic kidney disease (CKD) and its pathogenesis involves epithelial-to-mesenchymal transition (EMT) upon renal injury. Recombinant human erythropoietin (rhEPO) has been shown to display novel cytoprotective effects, in part by inhibiting transforming growth factor (TGF)-β1-induced EMT. Here, we evaluated the inhibitory effects of microparticles (MPs) derived from human EPO gene-transfected kidney mesenchymal stem cells (hEPO-KMSCs) against TGF-β1-induced EMT in Madin-Darby canine kidney (MDCK) cells and against TIF in mouse kidneys with unilateral ureteral obstruction (UUO).Methods: EMT was induced in MDCK cells by treatment with TGF-β1 (5 ng/mL) for 48 h and then inhibited by co-treatment with rhEPO (100 IU/mL), mock gene-transfected KMSC-derived MPs (MOCK-MPs), or hEPO-KMSC-derived MPs (hEPO-MPs) for a further 48 h. UUO was induced in FVB/N mice, which were then treated with rhEPO (1000 IU/kg, intraperitoneally, every other day for 1 week), MOCK-MPs, or hEPO-MPs (80 mg, intravenously). Alpha-smooth muscle actin (α-SMA), fibronectin, and E-cadherin expression were evaluated in MDCK cells and kidney tissues, and the extent of TIF in UUO kidneys was assessed by immunohistochemical staining.Results: TGF-β1 treatment significantly increased α-SMA and fibronectin expression in MDCK cells and decreased that of E-cadherin, while co-treatment with rhEPO, MOCK-MPs, or hEPO-MPs markedly attenuated these changes. In addition, rhEPO and hEPO-MP treatment effectively decreased phosphorylated Smad2 and Smad3, as well as phosphorylated p38 mitogen-activated protein kinase (MAPK) expression, suggesting that rhEPO and rhEPO-MPs can inhibit TGF-β1-induced EMT via both Smad and non-Smad pathways. rhEPO and hEPO-MP treatment also significantly attenuated the extent of renal TIF after one week of UUO compared to MOCK-MPs, with hEPO-MPs significantly reducing myofibroblast and F4/80+ macrophage infiltration as well as EMT marker expression in UUO renal tissues in a similar manner to rhEPO. Conclusions: Our results demonstrate that hEPO-MPs modulate TGF-β1-induced EMT in MDCK cells via the Smad2, Smad3, and p38 MAPK pathways and significantly attenuated renal TIF in UUO kidneys.
Determining Grasp Selection from Arm Trajectories via Deep Learning to Enable Functional Hand Movement in Tetraplegia
Authors: Bhagat Nikunj , King Kevin , Ramdeo Richard , Stein Adam , Bouton Chad
Published: July 2020

Background: Cervical spinal cord injury severely affects grasping ability of its survivors. Fortunately, many individuals with tetraplegia retain residual arm movements that allow them to reach for objects. We propose a wearable technology that utilizes arm movement trajectory information and deep learning methods to determine grasp selection. Furthermore, we combined this approach with neuromuscular stimulation to determine if self-driven functional hand movement could be enabled in spinal cord injury participants.Methods: Two cervical SCI participants performed arbitrary and natural reaching movements toward target objects in three-dimensional space, which were recorded using an inertial sensor worn on their wrist. Time series classifiers were trained to recognize the trajectories using either a Dynamic Time Warping (DTW) algorithm or a Long Short-Term Memory (LSTM) recurrent neural network. As an initial proof-of-concept, we demonstrate real-time classification of the arbitrary movements using DTW only (due to its implementation simplicity), which when used in combination with a high density neuromuscular stimulation sleeve with textile electrodes, enabled participants to perform functional grasping.Results: Participants were able to consistently perform arbitrary two-dimensional and three-dimensional arm movements which could be classified with high accuracy. Furthermore, it was found that natural reaching trajectories for two different target objects (requiring two different grasp types) were distinct and also discriminable with high accuracy. In offline comparisons, LSTM (mean accuracies 99%) performed significantly better than DTW (mean accuracies 86% and 83%) for both arbitrary and natural reaching movements, respectively. Type I and II errors occurred more frequently for DTW (up to 60% and 15%, respectively), whereas it stayed under 5% for LSTM. Also, DTW achieved online accuracy of 79%. Conclusions: We demonstrate the feasibility of utilizing arm trajectory information to determine grasp selection using a wearable inertial sensor along with DTW and deep learning methods. Importantly, this technology can be successfully used to control neuromuscular stimulation and restore functional independence to individuals living with paralysis.Trial registration: NCT, NCT03385005. Registered September 26, 2017, https://clinicaltrials.gov/ct2/show/NCT03385005
Assessing the acceptability of a text messaging service and smartphone app to support patient adherence to medications prescribed for high blood pressure: a pilot study.
Authors: Kassavou Aikaterini , Court Charlotte A , Chauhan Jagmohan , Brimicombe James , Bhattacharya Debbi , Naughton Felix , Hardeman Wendy , Mascolo Cecilia , Sutton Stephen
Published: July 2020

Aims and objectives. This paper describes a pilot non-randomised controlled study of a highly tailored 56-days text message and smartphone app prototype intervention to increase adherence to anti-hypertensive medication in primary care. The aim of this study was to evaluate the acceptability of the intervention and obtain patients views about the intervention content, delivery mode, and the mechanisms by which the intervention supported medication adherence. Methods. Patients diagnosed with hypertension were invited to the study via general practice text messages and were recruited face to face by the researcher team. Participants were asked to test the text message intervention for 28 consecutive days and switch to the smartphone app for 28 more days. Participants completed baseline and follow up questionnaires and took part in semi-structured telephone interviews. Digital log files captured patients’ usage of the intervention. Participant transcripts were analysed using thematic analysis. Descriptive statistics were used to summarize data from questionnaires and log files. A mixed methods analysis generated data to respond to the research questions. Results. 79 patients expressed interest to participate in this study, of whom 23 (64% male, 82% above 60 years old) were recruited to take part. With one drop-out, 22 participants tested the text message delivery mode (with 20 being interviewed) and four of them (17%) switched to the app (with 3 being interviewed). All participants engaged and interacted with the text message and app notifications, and most participants found the intervention content and delivery mode acceptable. They also self-reported that the interactive elements of the intervention motivated them to take their medications as prescribed. Conclusion. This study provides evidence that the digital intervention is acceptable by hypertensive patients recruited in primary care. Future research could usefully investigate its feasibility and effectiveness using rigorous research methods.
Physical exercise status of residents in Tibet, China：Data from 2018 National Health Service Survey
Authors: Li Qiwen , Wan Yang , Wang Guihua , Li Jiaqi , Deng Rengdan , Zhaxi Deji , Xiong Hai
Published: July 2020

Background: Physical inactivity is responsible for more than three million deaths worldwide. This research is to get a sense of the physical inactivity in Tibet, a region with an average elevation of over 4,000 meters, since the prevalence of physical inactivity in Tibet and its correlates factors were few studied and the physical exercise situation in the plateau area is a topic that needs to be understood in the field of public health.Methods: The Sixth National Health Service Survey in Tibet, a population-based door-to-door survey. A multistage stratified sampling design was used to select eligible households. We used Univariate analysis and Logistic regression analysis to examine status of physical exercise.Results: A total of 9,436 individuals were analyzed in this study with mean age of 40.81 years old. The prevalence of physical inactivity was 59.4%, and the highest with adults of 25~44 years old. It was showed that household register, educational degree, marital status, employment status, prefecture-level, smoking, drinking, health records and physical examination were associated with physical exercise ( p <0.001).Conclusion: Numerous residents in Tibet have a highly insufficient physical exercise, promoting the health awareness to engage Tibetan residents in physical exercise at the recommended level is conducive.
Stakeholders' perceptions of child and adolescent mental health services in a South African district – a qualitative study.
Authors: Babatunde Gbotemi Bukola , Rensburg André Janse van , Bhana Arvin , Petersen Inge
Published: July 2020

Background: In order to develop a district child and adolescent mental health (CAMH) plan, it is vital to engage with a range of stakeholders involved in providing CAMH services, given the complexities associated with delivering such services. Hence this study sought to explore multisectoral dynamics in providing CAMH care in one resource-constrained South African district as a case study, towards informing the development of a model for district mental health plan and generating lessons for mental health systems strengthening to support CAMH services using the Health Systems Dynamics (HSD) framework. HSD provides a suitable structure for analysing interactions between different elements within the health system and other sectors. Methods: Purposive sampling of 60 key informants was conducted to obtain an in-depth understanding of various stakeholders' experiences and perceptions of the available CAMH services in the district. The participants include stakeholders from the Departments of Health (DoH), Basic Education (DBE), community-based/non-governmental organizations and caregivers of children receiving CAMH care. The data was categorized according to the elements of the HSD framework. Results: The HSD framework helped in identifying the components of the health systems that are necessary for CAMH service delivery. At a district level, the shortage of human resources, un-coordinated CAMH management system, lack of intersectoral collaboration and the low priority given to the CAMH system negatively impacts on the service providers' experiences of providing CAMH services. Services users' experiences of access to available CAMH services was negatively impacted by financial restrictions, low mental health literacy and stigmatization. Nevertheless, the study participants perceived the available CAMH specialists to be competent and dedicated to delivering quality services but will benefit from systems strengthening initiatives that can expand the workforce and equip non-specialists with the required skills, resources and adequate coordination. Conclusions: The need to develop the capacity of all the involved stakeholders in relation to CAMH services was imperative in the district. The need to create a mental health outreach team and equip teachers and caregivers with skills required to promote mental wellbeing, promptly identify CAMH conditions, refer appropriately and adhere to a management regimen was emphasized.
Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain
Authors: García-Magro Nuria , Negredo Pilar , Martin Yasmina B. , Nuñez Angel , Avendaño Carlos
Published: July 2020

Background: Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.Methods: Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally.Results: GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.Conclusions: GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.
Collagen-dependent platelet dysfunction and its relevance to either mitochondrial ROS or cytosolic superoxide generation: a question about the quality and functional competence of long-stored platelets
Authors: Hosseini Ehteramolsadat , Hojjati Saba , gashti Safoora Afzalniaye , Ghasemzadeh Mehran
Published: July 2020

Background: Upon vascular damage, the exposed subendothelial matrix recruits circulating platelets to site of injury while inducing their firm adhesion mainly via GPVI-collagen interaction. GPVI also supports aggregatory and pro-coagulant functions in arterial shear rate even on the matrix other than collagen. Reactive oxygen species (ROS) modulate these stages of thrombosis; however augmented oxidant stress also disturbs platelet functions. Stored-dependent platelet lesion is associated with the increasing levels of ROS. Whether ROS accumulation is also relevant to collagen-dependent platelet dysfunction is the main interest of this study. Methods: Fresh PRP-PCs (platelet concentrates) were either stimulated with potent ROS-inducers PMA and CCCP or stored for 5 days. Intra-platelet superoxide (O2--) or mitochondrial-ROS and GPVI expression were detected by flowcytometery. GPVI shedding, platelet aggregation and spreading/adhesion to collagen were analyzed by western blot, aggregometry and fluorescence-microscopy respectively. Results: Mitochondrial-ROS levels in 5 days-stored PCs were comparable to those induced by mitochondrial uncoupler, CCCP while O2-- generations were higher than those achieved by PMA. Shedding levels in 5 days-stored PCs were higher than those induced by these potent stimuli. GPVI expressions were reduced comparably in CCCP treated and 5 days-stored PCs. Platelet adhesion was also diminished during storage while demonstrating significant reverse correlation with GPVI shedding. However, only firm adhesion (indicated by spreading or platelet adhesion surface area) was relevant to GPVI expression. Platelet adhesion and aggregation also showed reverse correlations with both O2-- and mitochondrial-ROS formations; nonetheless mitochondrial-ROS was only relevant to firm adhesion. Conclusion: As a sensitive indicator of platelet activation, GPVI shedding correlated with either simple adhesion or spreading to collagen, while GPVI expression was only relevant to platelet spreading. Thereby, if the aim of GPVI evaluation is to examine platelet firm adhesion, expression seems to be a more specific choice. Furthermore, the comparable levels of ROS generation in 5 days-stored PCs and CCCP treated platelets, indicated that these products are significantly affected by oxidative stress. Reverse correlation of accumulating ROS with collagen-dependent platelet dysfunction is also a striking sign of an oxidant-induced lesion that may raise serious question about the post-transfusion quality and competence of longer stored products.
A new traction method (traction ring) for colorectal endoscopic submucosal dissection: a retrospective study
Authors: Huang Xinyuan , Zhai Hui-Hong , Ji Ming , Li Peng , Niu Yinglin , Meng Fandong , Yu Li , Wang Yongjun , Zhao Haiying , Lv Fujing , Zhang Shutian
Published: July 2020

Background

Colorectal endoscopic submucosal dissection (ESD) is a challenging operation because it is often difficult to attain good visualization of the submucosal layer. Lots of traction methods have been developed to facilitate submucosal dissection, but still not widely applied. Therefore, we designed a new traction device "traction ring". This pilot study is to evaluate if traction ring is feasible and safe for colorectal ESD.
Methods

We retrospectively analyzed 20 patients with colorectal lesions who had undergone traction ring assisted ESD. The main outcome was the rate of en bloc resection, R0 resection rate, procedure time, resection time, intraoperative and postoperative complications.
Results

The median procedure time was 74.5 min (range 35–269 min.). The median resection time was 55 min (range 25–209 min.). The application of the traction system accounting for only 2.7% of the whole procedure time. Rate of en bloc resection was 95% (19/20). Rate of R0 resections was 90% (18/20). All traction rings were successfully settled and retrieved. No serious excessive intraoperative bleeding was observed. One patient was found perforation after treatment, no further intervention was required. No delayed complications were observed within one month after the operation.
Conclusions

This retrospective study demonstrated that the new countertraction method (traction ring) may become a safe, effective and simple way to assist ESD for colorectal lesions.
Neoadjuvant concurrent chemoradiotherapy followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery for low-lying rectal adenocarcinoma: a single center study
Authors: Lu Yen-Jung , Chen Chien-Hsin , Lin En-Kwang , Wu Szu-Yuan
Published: July 2020

Purpose: To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma.Methods and materials: A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U-test were used to make nonparametric comparisons.Results: Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 minutes and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested were 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. Conclusion: Neoadjuvant CCRT followed by TaTME-SPLS can be a safe and an effective sphincter-preserving procedure with acceptable morbidity rate for Asian patients with low-lying rectal adenocarcinoma.
Feasibility and Acceptability of the Family Centered Model to Manage and Prevent Non Communicable Diseases in Selected Communities of Lusaka Province”
Authors: Shankalala Perfect , Bosomprah Samuel , Chilengi Roma , Heimburger Douglas , Mutale Wilbroad
Published: July 2020

ObjectiveOur objective was to test the feasibility and acceptability of Family centered model in managing and preventing NCDs in the Zambian context. We used hypertension as our tracer NCD.ResultsFormative stage: Six major themes emerged during intervention design based on community conversation: (1) Willingness, (2) Importance of family support; (3) incentives for CHWs (4) trainings health workers (5) Basic Equipment (6) Medical supplies. Participants found FCM to be acceptable and needed in the community. They emphasized the need for training all people involved (HW, CHW and family members) and providing basic equipment to manage hypertension and other NCDs.Pilot Feasibility stage: We approached 9 families using an index patient identified at the clinic. One family declined to take part. So 8 families were screened with a total of 32 family members. Hypertension prevalence was 43.8% (14/32) among all those who were screened. During the pilot, four groups were formed based on the FCM, 3 out of the 4 groups managed to form household FCM. Each group had 4–6 members. CHW provided basic training to family members and followed up over a 3 months period, visiting weekly or when needed.
Identifying Critical Attributes and Attribute-Levels for a Discrete Choice Experiment on Oral Pre-Exposure Prophylaxis (PrEP) Delivery Among Young People in Cape Town and Johannesburg, South Africa.
Authors: Dietrich Janan Janine , Atujuna Millicent , Tshabalala Gugulethu , Hornschuh Stefanie , Mulaudzi Mamakiri , Koh Michelle , Ahmed Nadia , Muhumuza Richard , Ssemata Andrew , Otwombe Kennedy , Bekker Linda-Gail , Seeley Janet , Martinson Neil A , Terris-Prestholt Fern , Fox Julie
Published: July 2020

Background Oral Pre-Exposure Prophylaxis (PrEP) was approved for use in South Africa (SA) in 2017. The uptake and adherence of daily oral PrEP has been poor in high-risk populations in SA including adults and young people. We used a Discrete Choice Experiment (DCE) technique to identify critical attributes and attribute-levels to understand user preferences for daily and on-demand oral PrEP use among young people, including adolescents, in two South African cities. Methods Qualitative data were collected between September and November 2018 from 8 group discussions and 20 in-depth interviews with young people aged 13 to 24 years in Cape Town and Johannesburg. Participants were selected based on stratified (gender and age) purposive sampling. Using a semi-structured interview guide, interviewers discussed several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Transcripts were coded to identify context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. Results We enrolled 74 participants: 51% (n=38/74) male, median age of 18.5 [IQR=16-21.25] years, 91% (n=67/74) identified as heterosexual and 49% (n=36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). Conclusions There is limited methodological literature describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.
Corticosteroid Therapy of Patients in ICU with Coronavirus Disease 2019(COVID-19): A Single-center, Retrospective, Observational study
Authors: Ruan Zhengshang , Wei Ming , Xuan Si , Qian Aihua , Liu Lijun , Xu Bin , Xu Jing , Jiang Jinjun , Ren Rongrong , Zheng Junhua
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
Fatigue resistance and failure behavior of penetration and non-penetration laser welded lap joints
Authors: Guo Xiangzhong , Liu Wei , Li Xiqing , Shi Haowen , Song Zhikun
Published: July 2020

The fatigue resistance and failure behaviour of penetration 1.5 + 0.8-P and non-penetration 0.8 + 1.5-N laser welded lap joints prepared with 0.8 mm and 1.5 mm cold-rolled 301L plates were investigated. The weld beads showed a solidification microstructure of primary ferrite with good thermal cracking resistance, and their hardness was lower than that of the plates. The 1.5 + 0.8-P joint exhibited a better resistance to high-cycle fatigue failure, while the 0.8 + 1.5-N joint showed a higher resistance to low-cycle fracture. The failure modes of 0.8 + 1.5-N and 1.5 + 0.8-P joints were 1.5 mm and 0.8 mm lower lap plate fracture, respectively, and the primary cracks were initiated at welding fusion lines on the lap surface. There were long plastic ribs on the penetration plate fracture, but not on the non-penetration plate fracture. The fatigue resistance stress of the penetration and non-penetration plates in the crack initiation areas calculated based on the mean fatigue limits is 408 MPa and 326 MPa, respectively. The main reason for the difference in fatigue performance between the two laser welded joints was that the asymmetrical heating in the non-penetration plate thickness resulted in higher residual stress near the welding fusion line.
Preoperative prognostic factors associated with postoperative delirium in older people undergoing surgery: protocol for a systematic review and individual patient data meta-analysis
Authors: Buchan Tayler A , Sadeghirad Behnam , Schmutz Nayeli , Goettel Nicolai , Foroutan Farid , Couban Rachel , Mbuagbaw Lawrence , Dodsworth Benjamin T
Published: July 2020

Background: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes.Methods: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (≥ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach.Discussion: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients.
Dietary Fructose and Risk of Metabolic Syndrome in Chinese Residents Aged 45 and Above: Results From the China National Nutrition and Health Survey
Authors: pang shaojie , Song Pengkun , Qi Wentao , Yang Chun , Song Ge , Wang Yong , Zhang Jian
Published: July 2020

Background
A growing number of researches supported that dietary fructose was associated with all the key features of metabolic syndrome (MetS). However, there was no large epidemiological study among Chinese population although the prevalence of MetS increased sharply. This study explores the relationship between dietary fructose and MetS among Chinese residents aged 45 and above.
Methods
A total of 25528 participants (11574 males and 13954 females) were included in this nationwide representative cross-sectional study of China National Nutrition and Health Survey. Dietary fructose intake was assessed by 3-day 24-h dietary records. MetS was defined according to the International Diabetes Federation and Chinese Diabetes Society criteria.
Results
The consumption of dietary fructose for urban residents was 11.6 g/day and for rural residents was 7.6 g/day. Fruits and vegetables as well as their products were the main food sources. There was no association between dietary fructose intake and the risk of MetS in both urban (P = 0.315) and rural residents (P = 0.230) after adjustment for confounding factors. Moreover, for urban residents who participating in physical activity, the risk of MetS in the fourth quartiles (OR: 0.67; 95%CI: 0.52–0.86) was reduced compared with the first quartile. In the sensitivity analysis, the risk of MetS was also found a significant reduction in the fourth quartiles (OR, 95%CI: 0.67, 0.51–0.89; 0.63, 0.46–0.85; 0.74, 0.56–0.98) compared with the first quartile when excluding smokers, alcohol users, and underweight/obesity, respectively. And there was no association between dietary fructose intake and the risk of MetS after multivariate adjustment stratified by gender, smoking and alcohol use.
Conclusions
Under the current dietary fructose intake status, there was no association between dietary fructose intake and the risk of MetS among Chinese residents aged 45 and above. Physical activity and relatively low fructose intake may have a beneficial synergistic effect on MetS.
Honokiol Nanoscale Drug Delivery System Ameliorates the Cognitive Deficits in Tgcrnd8 Mice of Alzheimer’s Disease via Inhibiting Neuropathology and Modulating Gut Microbiota
Authors: Qu Chang , Li Qiao-Ping , Su Zi-Ren , Ip Siu-Po , Yuan Qiu-Ju , Xie You-Liang , Xu Qing-Qing , Yang Wen , Huang Yan-Feng , Xian Yan-Fang , Lin Zhi-Xiu
Published: July 2020

Background

Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer’s disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy. A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO.
Methods

Male TgCRND8 mice were administered with Nano-HO or HO at the same dosage (20 mg/kg) by oral gavage daily for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions with the Morris Water Maze test (MWMT).
Results

Nano-HO and HO could significantly improve cognitive deficits and inhibit neuroinflammation via suppressing the levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. In addition, Nano-HO and HO could modulate amyloid precursor protein (APP) processing and phosphorylation via suppressing β-secretase including β-site APP cleaving enzyme-1 (BACE-1) and phosphorylated APP (Thr 668), inhibiting γ-secretase including presenilin-1 (PS-1) and anterior pharynx-defective-1 (APH-1), as well as enhancing Aβ-degrading enzymes such as insulin degrading enzyme (IDE) and neprilysin (NEP). Moreover, Nano-HO remarkably inhibited tau hyperphosphorylation via decreasing the levels of p-tau (Thr 205) and p-tau (Ser 404), as well as regulating tau-related apoptosis proteins including caspase-3 and Bcl-2. Furthermore, Nano-HO and HO markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. On the other hand, Nano-HO and HO prevented the alterations on the composition of gut microbiota in TgCRND8 mice.
Conclusions

Nano-HO was more effective than regular HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO was also more potently modulate the gut microbiota community to protect its stability as compared with that of regular HO. Our results amply indicated that HO with nano-sized drug delivery system has good potential for further development into therapeutic agent for AD treatment.
Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
Authors: Desbois Anne-Claire , Marques Cindy , Lefèvre Leila , Barmo Serge , Lorenzo Camille , Leclercq Mathilde , Leroux Gaëlle , Comarmond Chloé , Chapelon Catherine , Domont Fanny , Vautier Mathieu , Saadoun David , Cacoub Patrice
Published: July 2020

Objective: To investigate the prevalence, clinical features and outcomes of coronavirus disease 2019 (COVID-19) among sarcoidosis patients. Methods: We retrospectively collected features of COVID-19 in a cohort of patients with sarcoidosis followed in a single tertiary university hospital. Results: Among 199 sarcoidosis patients [mean age 58.8 (±14) years, 86 (43.2%) men], 26 (13%) were diagnosed with COVID-19 [definite (n=7), probable (n=12) and possible (n=7)]. Twenty-four out of 26 patients (92%) had at least one comorbidity, and 11/26 (42%) had two or more comorbidities. Demographic and clinical features of COVID-19 positive patients were similar to those of COVID-19 negative patients. The administration of hydroxychloroquine or immunosuppressant was not associated with the occurrence or the severity of COVID-19. Four out of 26 (15.4%) COVID-19 positive patients required admission to hospital and two of them died. Hospitalized patients [mean age of 61 (±11.5) years] were receiving higher doses of long term treatment with corticosteroids than non-hospitalized patients; 4/4 had pulmonary and 2/4 cardiac involvement of sarcoidosis, and all one or more comorbidity. Conclusion: The prevalence of COVID-19 in sarcoidosis is slightly higher to that of the general population. Almost half of the COVID-19 positive patients have two or more comorbidities and about 15% present a severe course.
Nomogram to identify severe Coronavirus Disease 2019 (COVID-19) based on initial clinical and CT characteristics: a multi-center study
Authors: Yu Yixing , Wang Ximing , Li Min , Gu Lan , Xie Zongyu , Gu Wenhao , Xu Feng , Bao Yaxing , Liu Rongrong , Hu Su , Hu Mengjie , Hu Chunhong
Published: July 2020

Background: To develop and validate a nomogram for early identification of severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics.Methods: The initial clinical and CT imaging data of 217 patients with COVID-19 were analyzed retrospectively from January to March 2020. 217 patients with 146 mild cases and 71 severe cases were randomly divided into training and validation cohorts. Independent risk factors were selected to construct the nomogram for predicting severe COVID-19. Nomogram performance in terms of discrimination and calibration ability was evaluated using the area under the curve (AUC), calibration curve, decision curve, clinical impact curve and risk chart.Results: In the training cohort, the severity score of lung in the severe group (7, interquartile range [IQR]:5-9) was significantly higher than that of the mild group (4, IQR:2-5) (P < 0.001). Age, density, mosaic perfusion sign and severity score of lung were independent risk factors for severe COVID-19. The nomogram had a AUC of 0.929 (95% CI, 0.889-0.969), sensitivity of 84.0% and specificity of 86.3%, in the training cohort, and a AUC of 0.936 (95% CI, 0.867-1.000), sensitivity of 90.5% and specificity of 88.6% in the validation cohort. The calibration curve, decision curve, clinical impact curve and risk chart showed that nomogram had high accuracy and superior net benefit in predicting severe COVID-19.Conclusion: The nomogram incorporating initial clinical and CT characteristics may help to identify the severe patients with COVID-19 in the early stage.
Investigation and Analysis of the Differences Between the Medical Personnel’s and General Population’s View on the Doctor-Patient Relationship and Its Causes
Authors: Sang Tianqing , Zhou Hongli , Li Muhan , Li Wenting , Shi Haibo , Chen Haibin , Zhou Hongguang
Published: July 2020

Background: Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients’ medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP). Methods: This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. The MP and the GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon's Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data. Results: Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical stuff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP’s preference for their children's practice (p<0.05). Most MP hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR. Conclusion: The MP’s and GP’s views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.
GPNMB expression impacts prognosis and immune infiltration in cancers
Authors: Wang Yang , Chen Qiong
Published: July 2020

Background

Glycoprotein non-metastatic gene B (GPNMB) can regulate tumor progression by interacting with T cell function. However, the association between GPNMB and tumor-infiltrating immune cells and prognosis of various cancers is poorly understood.
Methods

We use the Oncomine and TIMER database to investigate GPNMB expression in multiple tumors. The PrognoScan database, Kaplan-Meier plotter are used to analyze tumor prognosis of GPNMB. R packages are used to performed multivariable cox regression analysis. We use TIMER and GEPIA database to explore the association between GPNMB expression and tumor immune infiltration levels, and immune cell markers. GPNMB related transcription factors and transcription-target networks are investigated via TTRUST database and GeneMANIA .
Results

A high level of GPNMB expression was significantly associated with poor prognosis in stomach adenocarcinoma (STAD). While, a high level of GPNMB expression was significantly associated with favorable prognosis in lung adenocarcinoma (LUAD). Besides, GPNMB expression levels can impact the prognosis in STAD and LUAD patients with lymph node metastasis. Moreover, GPNMB expression level has significant relationships with B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and DCs infiltrating levels in STAD and LUAD. Besides, various immune gene markers of STAD and LUAD are significantly related to GPNMB expression. In addition, the GPNMB related transcription factors are MITF and TP53. The transcript-target networks are mainly responsible for signal transduction in response to DNA damage, DNA damage response, signal transduction by p53 class mediator, mitotic G1 DNA damage checkpoint, G1 DNA damage checkpoint.
Conclusions

These results indicate that GPNMB is significantly associated with prognosis and immune infiltrating levels in various cancers patients, especially in STAD, LUAD patients. Multiple immune gene markers of STAD and LUAD are significantly related to GPNMB expression, especially monocyte, macrophage polarization, and functional T cells gene markers. Our study signifies that GPNMB plays an essential role in prognosis prediction and immune infiltration of STAD and LUAD.
Application of mini-invasive surgical instruments in transaortic myectomy for hypertrophic obstructive cardiomyopathy: A single-center experience with 168 cases
Authors: Ji Qiang , Wang YuLin , Yang Ye , Lai Hao , Ding WenJun , Xia LiMin , Wang Chun Sheng
Published: July 2020

Background: Septal myectomy has been a standard treatment option for patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug refractory symptoms. However, there are only a few experienced myectomy centers in the world so far, mainly because of high technical difficulty of myectomy. From our clinical experience, the use of the mini-invasive surgical instruments during myectomy may be beneficial to reduce the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for the treatment of patients with HOCM and drug refractory symptoms, and evaluates the early results following myectomy.Methods Between March 2016 and March 2019, consecutive HOCM patients were included in this analysis who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments. Intraoperative, in-hospital and follow-up results were analyzed.Results A total of 168 eligible patients (83 males, mean 56.8 ± 12.3 years) were included. Midventricular obstruction was recorded in 7 (4.2%) patients. All included patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 minutes. Nine (5.4%) patients received repeat aortic cross-clamping during surgery. Surgical mortality was 0.6%. Five (3.0%) patients developed complete atrioventricular block and required permanent pacemaker implantation. The median follow-up time was 6 months. No follow-up deaths occurred with a significant improvement in New York Heart Association functional status. The maximum gradients decreased sharply from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 2 2.6 mmHg, p<0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p<0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p<0.001).Conclusions The use of the mini-invasive surgical instruments may be beneficial to reduce the technical difficulty of transaortic septal myectomy procedure. Transaortic septal myectomy using the mini-invasive surgical instruments may be associated with favorable results.
Gravimetric Geoid Modeling from the Combination of Satellite Gravity Model, Terrestrial and Airborne Gravity Data: A Case Study in the Mountainous Area, Colorado
Authors: Jiang Tao , Dang Yamin , Zhang Chuanyin
Published: July 2020

Constructing a high precision and high resolution gravimetric geoid model in the mountainous area is a quite challenging task because of the high, rough nature of topography and the geological complexity. One way out is to use as many gravity observations from different sources as possible such as satellite, terrestrial and airborne gravity data, thus the proper combination of heterogeneous gravity datasets is critical. In a rough topographic area in Colorado, we computed a set of gravimetric geoid models based on different combination modes of satellite gravity models, terrestrial and airborne gravity data using the spectral combination method. The gravimetric geoid model obtained from the combination of satellite gravity model GOCO06S and terrestrial gravity data agrees with the GPS leveling measured geoid heights at 194 benchmarks in 5.8 cm in terms of the standard deviation of discrepancies, and the standard deviation reduces to 5.3 cm after including the GRAV-D airborne gravity data collected at ~6.2 km altitude into the data combination. The contributions of airborne gravity data to the signal and accuracy improvements of the geoid models were quantified for different spatial distribution and density of terrestrial gravity data. The results demonstrate that, although the airborne gravity survey was flown at a high altitude, the additions of airborne gravity data improved the accuracies of geoid models by 13.4% - 19.8% in the mountainous area (elevations > 2000 m) and 12.7% - 21% (elevations < 2000 m) in the moderate area in the cases of terrestrial gravity data spacings are larger than 15 km.
Statistical Analysis of Ionospheric Total Electron Content (TEC): Long-Term Estimation of Extreme TEC in Japan
Authors: Nishioka Michi , Saito Susumu , Tao Chihiro , Shiota Daikou , Tsugawa Takuya , Ishii Mamoru
Published: July 2020

Ionospheric total electron content (TEC) is one of the key parameters for users of radio-based systems, such as the Global Navigation Satellite System, high-frequency communication systems, and space-based remote sensing systems, since total ionospheric delay is proportional to TEC through the propagation path. It is important to know extreme TEC values in readiness for hazardous ionospheric conditions. The purpose of this study is to estimate extreme TEC values with occurrences of once per year, ten years, and hundred years in Japan. In order to estimate the extreme values of TEC, a cumulative distribution function of daily TEC is derived using 22 years of TEC data from 1997 to 2018. The extreme values corresponding to once per year and ten years are 90 and 130 TECU, respectively, in Tokyo, Japan. On the other hand, the 22-year data set is not sufficient to estimate the once-per-hundred-year value. Thus, we use the 62-year data set of manually scaled ionosonde data for the critical frequency of the F-layer (foF2) at Kokubunji in Tokyo. First, we study the relationship between TEC and foF2 for 22 years and investigate the slab thickness. Then the result is applied to the statistical distribution of foF2 data for 62 years. The result shows that the once-per-100-year TEC is about 190 TECU at Tokyo. The value is also estimated to be 230 TECU in Kagoshima and 150 TECU in Hokkaido, in the southern and northern parts of Japan, respectively.