bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of dental implants inserted in clinical studies using static implantation guides: a systematic review and a meta-analysis
Authors: Gaubys Algimantas , Sakalys Dovydas , Krukis Martynas Mantas , Janužis Gintaras
Published: May 2020

Background One of the main tasks of dental implantation is the precise insertion of the implant into the edentulous jaw. The purpose of a study was to determine the accuracy of implants inserted using static implantation guides in different conditions.Methods A search for clinical studies was performed in the PubMed databasis. The implantation procedure had to be performed on humans in vivo by using a static surgical guide. Pre and postsurgical CT scans were compared to evaluate the deviation of implants. A meta-analyses was performed to calculate the mean implant collar, apex, depth and axis deviations. A meta-regression analyses was performed by grouping study subgroups according to the method of surgery, implant insertion, jaw, guide support tissue, and the method of guide fixation.Results 19 studies were included in the meta-analysis. Data on 1872 implants were analyzed. Mean deviation was 1.25 mm (95% CI: 1.00, 1.51) at the implant entry point and 1.52 mm (95% CI: 1.18, 1.86) at the apex. Mean axis deviation was 3.47o (95% CI: 3.01, 3.94). Depth deviation was 0.15 mm (95% CI: -0.36, 0.66). The following factors had a positive influence on the implant precision: open surgical technique, fully guided implant insertion and fixation of the surgical guide.Conclusions The surgical technique, implant insertion method, jaw, guide supporting tissue and fixation has an effect on the deviation of inserted implants.
Vitamin D Supplementation in Obese Sri Lankan Children: A Randomized Controlled Trial
Authors: Samaranayake Dulani DL , Adikaram Shyamini GS , Atapattu Navoda , Kendaragama Lakshika D , Senevirathen Tharika N , Jaasekera Hasika D , Wickramasinghe Vithanage Pujitha
Published: May 2020

Background Micronutrient deficiencies are identified among obese individuals. Vitamin D deficiency is prevalent in obese children, and is hypothesized to cause insulin resistance and metabolic abnormalities. This study aimed to determine the effect of vitamin D supplementation on obesity and related metabolic abnormalities among obese Sri Lankan children.Methods A triple-blind randomized controlled trial was conducted among vitamin D deficient (< 20 ng/ml), obese children (n = 96). Children were randomly allocated to three intervention arms - treatment arm receiving weekly vitamin D2 50,000 IU; supplementation arm receiving 2500 IU weekly and control arm receiving placebo. Anthropometry, percentage fat mass (%FM) and blood pressure were assessed and fasting blood glucose, fasting insulin, lipid profile, ALT, AST, vitamin D, parathyroid hormone and hs-CRP and OGTT with 2-hour random blood glucose and insulin was performed at baseline and after 24 weeks of treatment. Ethics Review Committee of Faculty of Medicine, University of Colombo approved the protocol.Results Waist circumference Z-score, %FM and serum calcium significantly improved across all three arms, ALT significantly improved in treatment and supplementation arms while, BMI Z-score, PTH and vitamin D significantly improved in the treatment arm. Biceps (p = 0.035) and subscapular (0.048) skin fold thickness, vitamin D (p = 0.004) and ALT (p = 0.012) significantly improved in the treatment arm.Conclusions A strict dietary and physical activity regimen could improve some of the anthropometric, body composition and metabolic profiles, but high dose vitamin D, enhances those improvements. Therefore high dose vitamin D seems to potentiate management outcomes of obese children with vitamin D deficiency.Trial registration The study was registered at the Sri Lanka Clinical Trials Registry (SLCTR/2015/017) on 12th September 2015 at https://slctr.lk/trials/slctr-2015-017.
Impact of Diabetes Mellitus on Left Ventricular Longitudinal Function of Patients with Non-Ischemic Dilated Cardiomyopathy
Authors: Tanaka Hidekazu , Tatsumi Kazuhiro , Matsuzoe Hiroki , Matsumoto Kensuke , Hirata Ken-ichi
Published: May 2020

Background
Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear.
Methods
We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure.
Results
GLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan-Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index.
Conclusion
Management of DCM patients with T2DM may be improved by using GLS guidance.
Physiotherapists’ Awareness of Risk of Bone Demineralisation and Falls in People Living with HIV and their Perceptions about Fall Risk Management: A Qualitative Study
Authors: Charumbira Maria Yvonne , Berner Karina , Louw Quinette
Published: May 2020

Background: Recent research has indicated a seemingly increased propensity for both falls and accelerated bone loss in people living with HIV (PLWH). Physiotherapists play a crucial role in optimising function and quality of life of PLWH through prevention of falls and reducing the harm that results. Aim: This study aimed to explore physiotherapists’ awareness of falls risk and accelerated bone demineralisation in PLWH and their perceptions about current falls prevention in the care of PLWH in selected regions of sub-Saharan Africa. Method: An interpretative exploratory qualitative research method with a phenomenological approach was employed to explore physiotherapists’ perceptions and experiences regarding bone health and falls in PLWH. In-depth semi-structured telephonic interviews were used to collect data from 21 physiotherapists working in primary HIV care. Transcribed interview data were coded in Atlas.ti.8 ® and analysed using inductive thematic analysis. Results: The primary study revealed a lack of awareness by physiotherapists of falls risk and bone demineralisation in PLWH. As such, physiotherapists did not link falls or fractures to HIV or antiretroviral therapy (ART) when they did observe such events during their general patient assessments. However, in retrospect, some physiotherapists were able to recognise risk factors linked to falls in those with HIV. Current services for falls prevention, as perceived by the physiotherapists, were sub-optimal. Conclusion: Physiotherapists may need to be more aware of the potential risk of falls and bone demineralisation in PLWH and routinely assess for these phenomena in both older and younger PLWH. Key words: Accidental falls, Bone mineral density, HIV, physiotherapists, sub-Saharan Africa
CD4- and CD8-Expressing Cells in the Chambers of Normal, Cataract and Uveitic Eyes: A Comparative Study in Dogs
Authors: Maślanka Tomasz , Ziółkowski Hubert , Garncarz Jacek , Ziółkowska Natalia
Published: May 2020

Background The eye chambers constitute an immunologically privileged compartment. The presence of CD4+ and CD8+ cells in the chambers of normal and cataract eyes is a research problem that so far has been explored only fragmentarily. The first aim of our research was to determine whether CD4+ and CD8+ cells are present in the normal chambers of the eye in dogs, and if so, what the relative and absolute counts of these cells are. Another objective was to verify the hypothesis that uncomplicated cataract may be associated with the local recruitment of CD4+ and CD8+ cells.Results The presence of CD4+ and CD8+ cells was detected in aqueous humor (AH) samples of normal and cataract eyes. However, on average only 55 and 236 events for combined subsets of CD4+ and CD8+ cells were collected for the entire volume of AH from normal and cataract eyes, respectively. The statistical analysis did not reveal significant differences in the percentage and absolute number of CD4+ cells between normal and cataract eyes. However, the values of these parameters in AH samples from cataract eyes were approximately 2- and 3-fold higher than in normal eyes, respectively. The mean percentage and absolute count of CD8+ cells increased approximately by 2.7- and 6-fold, respectively, in AH samples from cataract eyes compared to normal ones. The absolute count, but not the percentage, of CD4+ and CD8+ cells in AH of uveitic eyes was approximately 5- and 3-fold higher than in cataract eyes.Conclusions The results indicate that CD4+ and CD8+ cells occur constitutively in the normal chambers of the eye in dogs. However, considering the extremely low abundance of these cells, it needs to be concluded that both of these cell populations appeared in trace amounts. The development of uncomplicated cataract in dogs may not be immunologically neutral in terms of the local immune response, but it may be associated with the recruitment of CD8+ cells into the eye chambers. This event does not seem to be of an inflammatory nature because it appears on a scale a few times smaller than in the course of uveitis.
Objective Measures of Functional Outcome in Recovery from Open Lower Limb Fractures – A Report from an Ortho-Plastic Research Clinic
Authors: I Pallister , Handley Gregory Jack , Maggs Sharon , Davies Ann-Marie , Kyle Amanda , Bodger Owen , Dafydd Hywel
Published: May 2020

BACKGROUNDOpen lower limb fractures are serious, potentially life-changing injuriesrequiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery.Our hypothesis was that objective measures combining strength, agility and balance would better reflect recovery than isolated parameters (e.g. range of motion) and would compare well to patients’ perceived recovery.METHODSAdultopen lower limb fracture patients were followed-up at 6 and 12 weeks, 6, 9 and 12 months post-injury. The mechanism,injurypattern, age, gender and treatment were recorded. Isolated parameter objective functional outcome measures (OFOMs)(range of movement and MRC strength grade) were compared to combined OFOMs(timed up and go (TUAG), comfortable and fast gait speed (CGS and FGS), Edgren Side Step Test(ESST) and Single Leg balance. Patient reported outcomes were recorded (Global Perceived Effect (GPE) scoreand Disability Rating Index (DRI)). RESULTS68 patients (54 male) with a medianage of 45 years (range 20-75). Neither range of movement,strength nor Single Leg balance consistently improved with time. TUAG, ESST, CGS, FGS and GPE scoresshowed consistent improvement, with TUAG and FGS showing highest proportion of improving results at each time-point. Patients’ estimation of recovery paralleled these measures with all but 2 patients achieving the minimum clinical important difference in DRI by 12 months compared to baseline. However, the GPE score compared favourably withthe DRI having a higher proportion of improving responses at each time-point. DISCUSSIONFunctional recovery is a key determinant in patients returning to work, providing for themselves and their family or resuming independent living for older patients. This study has demonstrated time-related improvements in combined OFOMs measuringmobility, strength, agility and balance paralleling patients’ perception of recovery in the 12 months after open lower limb fractures. Over the same time-frame, the simple GPE score compared favourably with the DRI. Such parameters could become part of a defined core outcomes set. Focussing rehabilitation towards these combined OFOMs may help hasten recovery.Trial registrationSouth West Wales REC 06/WMW02/10)
Association Between Morphologic Grading and Implantation Rate of Euploid Blastocyst
Authors: Lou Hua , Li Na , Guan Yichun , Zhang Yuchao , Hao Dayong , Cui Shihong
Published: May 2020

Objective To determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles.Design: Retrospective cohort study.Setting: Single university-based fertility centerPatient(s): Women aged 25–40 years undergoing euploid SET from January 2017 to December 2019 were identified.Main Outcomes Measure(s): Implantation rate (IR)Result(s): A total of 271 euploid SET cycles were included. The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality embryos (79.31% vs. 48%; adjusted odds ratio [OR] 3.269; 95% confidence interval [CI] 1.518–7.040). The OR remained significant after adjusting for maternal age, body mass index (BMI), type of infertility, basal follicle-stimulating hormone (FSH), AMH (anti-Müllerian hormone), peak endometrial thickness, type of SET cycle and day of blastocyst biopsy. According to post hoc analysis of age and the day of trophectoderm (TE) biopsy, the implantation rates in women aged < 35 years were higher after good-quality blastocyst transfer than poor-quality blastocyst transfer (80.39% vs. 48.62%, P = 0.003). Logistic regression analyses that adjusted for these variables identified higher implantation rates (OR 3.478, 95% CI 1.530–7.908) for good-quality blastocysts than for blastocysts that underwent poor-quality cycles, but not in women aged ≥ 35 years (71.43% vs. 62.50%, P = 0.402) (Table 2). The implantation rates were higher among women with good-quality blastocysts on both day 5 and day 6 of TE biopsy than among those with poor-quality blastocysts (day 5, 80.43% vs. 55.77%, P = 0.017; day 6, 75.00% vs. 42.47%, P = 0.074). Day 5 euploid blastocysts had no significant difference in implantation potential compared with similarly graded day 6 euploid blastocysts.Conclusions: Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.
Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dkk1 to activate Wnt/β-catenin pathway
Authors: Peng Zhi , Lou Zhenkai , Li Zhongjie , Li Shaobo , Yang Kaishun , Lu Sheng , Li Chao
Published: May 2020

Background:

Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling.
Methods:

The exosomes were extracted from BMSCs and labeled by PKH-67, and then incubated with hFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of hFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blot. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blot.
Results:

Here we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted hFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to hFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway.
Conclusion:

BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.
Metagenomic insights into the diversity of carbohydrate-degrading enzymes in the yak fecal microbial community
Authors: Gong Ga , Zhou Saisai , Luo Runbo , Gesang Zhuoma , Suolang Sizhu
Published: May 2020

Background: As a special herbivorous ruminant, yak is supposed to utilize the gastrointestinal microbiota to digest plant materials. Although the cellulolytic bacteria of yak rumen have been reported, there is still limited information about whether carbohydrate metabolizing enzymes in its intestinal flora are abundant for the degradation of complex lignocellulosic biomass.

Results: Here, this study aimed to decode the structure and function of yak fecal microbiota using deep metagenome sequencing. A comprehensive gene catalog comprising 4.5 million microbial genes was established and functionally annotated to characterize the primary metabolic potential of the microbiome based on metagenomic assemblies from 92 Gb sequencing data. A full spectrum of genes encoding carbohydrate-active enzymes were identified and about three-quarters of these genes assigned to a wide range of enzyme families were involved in the breakdown of complex dietary carbohydrates, including 120 families of glycoside hydrolases, 25 families of polysaccharide lyases, and 15 families of carbohydrate esterases. Inference of taxonomic assignments to the carbohydrate-degrading enzymes revealed the major microbial contributors were the members of Firmicutes and Bacteroidetes, both of which were also the most dominating bacterial populations in the yak fecal microbiome. Metagenomic binning further reconstructed 86 prokaryotic genomes, and a highly diversified profile of glycoside hydrolases associated with plant-derived polysaccharide degradation was also identified in these uncultured genomes, many of which were novel species with highly fibrolytic capability.

Conclusions: Our findings shed light on a great diversity of carbohydrate-degrading enzymes in the yak gut microbial community and uncultured species, providing a useful genetic resource for future studies on the discovery of novel enzymes with industrial potential.
Zymosan Promotes Proliferation, Candida albicans Adhesion and IL-1β Production of Oral Squamous Cell Carcinoma In Vitro
Authors: CHEN XU , Luo Qingqiong , Ding Jieying , Yang Meng , Zhang Ruiyang , Chen Fuxiang
Published: May 2020

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), and the effect of zymosan, a component of yeast cell wall, on oral cancer remains unclear. Cell proliferation assay was performed with CCK-8 to evaluate the effect of zymosan on proliferation of OSCC cell lines including WSU-HN4, WSU-HN6 and CAL-27, and potential mechanism was explored by quantitative real-time PCR, immunofluorescence assay and western blot. Cell adhesion assay was conducted to determine the adhesion of Candida albicans to OSCC cells, and related gene expression and protein was detected. Also, the proinflammatory cytokines including IL-6, IL-8, TNF-α and IL-1β from OSCC cells were determined by ELISA. In current study, zymosan (ZYM) promotes proliferation of OSCC cell lines including WSU-HN4, WSU-HN6 and CAL-27 by CCK-8 assay via TLR2/MyD88 pathway. By cell adhesion assay, the number of Candida albicans per oil field significantly increased in ZYM-treated OSCC cells compared to controls. When treated with zymosan, OSCC cells secreted significantly more pro-inflammatory cytokine IL-1β, which could enhance inflammation in oral cancer microenvironment. Zymosan from fungi cell wall promotes proliferation, Candida albicans adhesion and IL-1β production of oral squamous cell carcinoma by in-vitro experiments.
Distinct eGFR trajectories are associated with risk of myocardial infarction in people with diabetes or pre-diabetes
Authors: Zuo Yingting , Wang Anxin , Chen Shuohua , Tian Xue , Wu Shouling , He Yan
Published: May 2020

Background

The relationship between estimated glomerular filtration rate (eGFR) trajectories and myocardial infarction (MI) remains unclear in people with diabetes or prediabetes. We aimed to identify common eGFR trajectories in people with diabetes or prediabetes and to examine their association with MI risk.
Methods

The data of this analysis was derived from the Kailuan study, which was a prospective community-based cohort study. The eGFR trajectories of 24,723 participants from year 2006 to 2012 were generated by latent mixture modeling. Incident cases of MI occurred during 2012 to 2017, confirmed by review of medical records. Cox proportional hazards models were used to calculate hazard ratios (HR) and their 95% confidence intervals (CIs) for the subsequent risk of MI of different eGFR trajectories.
Results

We identified 5 distinct eGFR trajectories, and named them as low-stable (9.4%), moderate-stable (31.4%), moderate-increasing (29.5%), high-decreasing (13.9%) and high-stable (15.8%) according to their range and pattern. During a mean follow-up of 4.61 years, there were a total of 235 incident MI. Although, the high-decreasing group had similar eGFR levels with the moderate-stable group at last exposure period, the risk was much higher (adjusted HR, 3.43; 95%CI, 1.56–7.54 versus adjusted HR, 2.82; 95%CI, 1.34–5.95). Notably, the moderate-increasing group had reached to the normal range, still had a significantly increased risk (adjusted HR, 2.55; 95%CI, 1.21–5.39).
Conclusions

eGFR trajectories were associated with MI risk in people with diabetes or prediabetes. Emphasis should be placed on early and long-term detection and control of eGFR decreases to further reduce MI risk.
Anti-PD1/PDL1 antibodies plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma
Authors: Qian Jiong , Lin Wu , Wang Haohao , Mao Chenyu , Jiang Haiping , Teng Lisong , Xu Nong
Published: May 2020

Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) have a poor prognosis with few treatment options. Immunotherapy was suggested as a promising treatment for ESCC from some clinical trials. Here we collected clinical results from 23 patients who were received anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy as first line therapy with advanced ESCC, to analyze this combined therapy’s efficacy on advanced ESCC. Methods: Results of 23 Patients started treatment from December 15th, 2017 to September 27th, 2019 (12 patients were enrolled in phase II clinical trials, 11 patients were treated by physician’s choice regiment) of anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy on advanced ESCC as first line treatment were collected. Regiments were either anti-PD1 or anti-PDL1 mAbs plus traditional chemotherapy (cisplatin/5-fluorouracil (5-FU), Paclitaxel/ cisplatin, Paclitaxel/carboplatin or Paclitaxel/ 5-FU) every 3 weeks for six cycles, followed by maintenance therapy with anti-PD1/PDL1 mAbs. Objective response and safety profiles were observed as well as progression-free survival(PFS), overall survival(OS) and duration of response. Results: Of the 23 patients, 18 (78.3%) responded to treatment: 15 partial and 3 complete response. 4 patients had stable disease and 1 patient had progressive disease. The median time to response was 1.4 months (range, 1.4 months – 2.8 months). Treatment-related adverse events occurred in all patients but 3-4 grade immune-mediated adverse events occurred in only one patient. As of April 10th, 2020, the Objective response rate was 78.3%, the median PFS was 15.5 months and the median OS was 21.5 months. No treatment-related deaths were observed. Conclusions: Anti-PD1/PDL1 antibodies plus chemotherapy as the first-line treatment for advanced ESCC showed promising results with manageable adverse events and worthy of further study.
“One-stop shop”: Safety and efficacy of combining atrial septal defect occlusion and left atrial appendage closure for patients with atrial septal defect and atrial fibrillation.
Authors: zhihui zhang , qing yao , haiyun Huang , ping zhu , xiang xu , zhiyuan Song , huakang Li
Published: May 2020

Background: One-stop occlusion (combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure) in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF.Methods: We recruited inpatients with AF and ASD/PFO between August 2014 and April 2019. Preoperatively, they underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) to determine the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 6 months, and the TTE and TEE were evaluated regularly.Results: Forty-nine patients (age, 65.6±9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They underwent simultaneous LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the plug devices for ASD occlusion were 14.2±7.7 and 25.4±8.5 mm, respectively. The mean PFO size was 3.5±0.4 mm. The mean maximal LAA orifice width and depth were 20.5±3.4 and 28.3±3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1±2.9 mm). Postoperatively, all patients took oral anticoagulants for 6 months, and their mean postoperative follow-up duration was 29.0±12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO plug devices. At 45-60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients developed occluder thrombosis (warfarin and novel oral anticoagulants were used, respectively). The anticoagulant therapy was adjusted, and TEE showed that the thrombus disappeared at 6 months after operation.Conclusion: One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.
Wogonin Inhibits in vitro Herpes Simplex Virus Type 1 and 2 Infection Through Modulating Cellular NF-κB and MAPK Pathways
Authors: Chu Ying , Lv Xiaowen , Zhang Longfeng , Fu Xingli , Song Siwei , Su Airong , Chen Deyan , Xu Lianhong , Wang Yongfang , Wu Zhiwei , Yun Zhihua
Published: May 2020

Background Wogonin, a naturally flavonoid-like chemical compounds, has exhibited anti-inflammatory, anti-tumor, anti-viral, neuroprotective, and anxiolytic effects through modulating a variety of signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPK). In this study, its antiviral effect against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) replication has been investigated.Results The evidence showed that wogonin could suppress HSV-1 and − 2-induced cytopathogenic effect (CPE) and reduce viral RNA transcription, protein synthesis, and titers of infectious virion particles formation in a dose-dependent manner. Time-of-drug-addition assay demonstrated that wogonin acted as a viral post-entry inhibitor. It was also found that wogonin significantly reduced HSV-induced NF-κB and MAPK pathways activation, which were proved to be significant for viral replication previously.Conclusions Our results suggested that anti-herpes effect of wogonin may be mediated by its modulation of cellular NF-κB and JNK/p38 MAPK pathways, implying its potential application as an anti-HSV agent.
Impact of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: a randomized clinical trial
Authors: Montero Eduardo , López Mercedes , Vidal Honorato , Martínez María , Marrero Jorge , Virto Leire , Herrera David , Zapatero Antonio , Sanz Mariano
Published: May 2020

Background
Although there is evidence of positive effect of periodontal therapy on systemic inflammation, this response is highly variable among subjects. It was the aim of this clinical investigation to determine the impact of periodontal treatment on systemic markers of inflammation in patients with metabolic syndrome (MetS) and periodontitis.
Methods
In this parallel-arm, double blind, randomized controlled clinical trial, 63 patients with MetS and severe periodontitis were randomly assigned to receive intensive periodontal treatment (IPT; scaling and root planing plus azithromycin 500 mg, q.d., for three days) or minimal periodontal treatment (MPT; supragingival professional mechanical plaque removal plus a placebo). The primary outcome was the impact of the tested interventions on hs-CRP serum levels at 6 months. As secondary outcomes, differences in the levels of cytokines, markers of prothrombotic states, carbohydrate and lipids metabolism, as well as blood pressure, were measured at 3 and 6 months after therapy.
Results
The ITT population consisted on 63 subjects randomly assigned to either MPT (n = 31) or IPT (n = 32) groups. At baseline, mean hs-CRP was 3.9 mg/L (standard deviation, SD = 2.9) and 3.9 mg/L (SD = 3.4), respectively, and no significant differences in their cardiometabolic risk profiles were detected between groups. After 6 months, unadjusted mean hs-CRP were 2.9 mg/L (standard error, SE = 0.4) and 4.0 (SE = 0.8), respectively. Adjusting for baseline hs-CRP, sex, age, smoking status and body mass index, hs-CRP was 1.2 mg/L (95% confidence interval, [CI 0.4; 2.0]; p = 0.004) lower in the IPT group than in the MPT group. In the secondary outcomes, significant reductions in IL-1β, TNF-α, HbA1c and blood pressure were observed in the IPT group at 3 months, when compared to the MPT group.
Conclusion
Effective periodontal treatment significantly reduced hs-CRP after 6 months in patients with MetS and severe periodontitis. Periodontal therapy might be useful to reduce cardiovascular risk in these patients.
Trial registration:
ClinicalTrials.gov Registration Number: NCT03960216.
Comprehensive treatment of critical coronavirus disease 2019: a single-center retrospective case series from Wuhan
Authors: Huang Ke , Zhang Yi , Li Min , Feng Yingying , Yu Xin , Cai Ying , Xia Jingen , Duan Jun , Zhan Qingyuan
Published: May 2020

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has now spread worldwide. This study aimed to provide a reference for comprehensive treatment, personal protection, and team management of patients with critical COVID-19. Methods: The study included critical COVID-19 cases at a single centre in Wuhan, China. We retrospectively analysed data on symptoms, laboratory tests, radiology findings, treatment, and outcomes. Air samples and environmental surface swabs in the isolation ward were tested for SARS-CoV-2.Results: Fourteen critically ill patients (mean age 62.1 years) were treated between February 4, 2020 and April 6, 2020. Less than half had underlying diseases, including hypertension (n=6, 42.9%) and diabetes (n=4, 28.6%). Laboratory tests showed decreased lymphocyte levels and increased serum ferritin and inflammatory cytokine levels. More than half of the patients received antiviral drugs, including lopinavir/ritonavir (n=10; 71.4%) and arbidol (n=6, 42.9%). Eight patients (57.1%) received convalescent plasma, and 12 (85.7%) received systemic glucocorticoids. Eleven (78.6%) received high-flow nasal cannula oxygen therapy, five (35.7%) received non-invasive positive pressure ventilation, seven (50.0%) received invasive positive pressure ventilation, and three (21.4%) received extracorporeal membrane oxygenation. By April 6, 2020, nine (64.3%) patients were discharged, four remained in hospital, and one had died. All air samples tested negative for SARS-CoV-2. Of 128 environmental surface swabs, one gastric tube swab and one anal tube swab were positive for SARS-CoV-2. All oropharyngeal swabs taken from medical staff tested negative for SARS-CoV-2.Conclusions: Individualised comprehensive treatment, appropriate personal protection, and teamwork may improve the prognosis in patients with COVID-19 who are critically ill.
The role of Pirfenidone in the treatment of interstitial pneumonia with autoimmune features
Authors: Chen Tao , Li Qiu-Hong , Zhang Yuan , Yin Cheng-Sheng , Weng Dong , Zhou Ying , Hu Yang , Shi Jing-Yun , Chen Ya-Nan , Ye Shuang , Wang Xiao-Dong , Wu Chun-Yan , Huang Yan , Zhang Ai-Hong , Li Huiping
Published: May 2020

Rationale: No study indicated whether pirfenidone is appropriate for treatment of Interstitial pneumonia with autoimmune features (IPAF) patients. Objective: To evaluate the efficacy and safety of pirfenidone in the treatment of IPAF.Methods: The clinical data of 184 patients who met the diagnostic criteria of IPAF was selected. Those patients were assigned to pirfenidone treatment group (n=81) and control group (n=103). The baseline data and diagnostic characteristics of patients were retrospectively collected. Pulmonary function and prednisone dose were analyzed by mix-effect model.Results: 1. Baseline data: Forced vital capacity (FVC%, P< 0.001) and diffusion capacity of the lung for carbon monoxide (DLCO%, P= 0.003) of predicted values in the pirfenidone group were lower than those in the control group. 2. Diagnostic characteristics: There was no significant difference of diagnostic characteristics between two groups. 3. Therapeutic evaluation: The volume of FVC in pirfenidone group was increased by 0.0390 L/year, while that was decreased by 0.0769 L/year in the control group (P=0.038). 4. Subgroup analysis: Pirfenidone with dosage > 600 mg/day (P = 0.010) and medication course of treatment longer than 12 months (P = 0.007) showed superior therapeutic effects. 5. Dose of prednisone: During the period of 12-40 months, prednisone dose was reduced by 6.27 mg per day in pirfenidone group, compared with control group. 6. Side effects: A total of 17 patients (19.32%) experienced side effects after taking pirfenidone.Conclusion: Pirfenidone (600-1800 mg/day) can improve FVC of pulmonary function and help to reduce prednisone dose in IPAF patients. It contains controllable side effects.
Parathyroid hormone (1-34) promotes the effects of 3D printed scaffold-seeded bone marrow mesenchymal stem cells on meniscus regeneration
Authors: Zhao Wen , Zou Tong , Cui Hao , Lv Yangou , Gao Dengke , Ruan Chenmei , Zhang Xia , Zhang Yihua
Published: May 2020

Background
Cell-based tissue engineering represent a promising management for meniscus repair and regeneration. The present study aimed to investigate whether the injection of parathyroid hormone (PTH) (1–34) could promote the regeneration and chondroprotection of 3D printed scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in a canine total meniscal meniscectomy model.
Methods
3D printed poly(e-caprolactone) scaffold seeded with BMSCs was cultured in vitro, and the effects of in vitro culture time on cell growth and matrix synthesis of the BMSCs-scaffold construct were evaluated by microscopic observation and cartilage matrix content detection at 7, 14, 21, and 28 days. After that, the tissue-engineered meniscus based on BMSCs–scaffold cultured for the appropriate culture time was selected for in vivo implantation. Sixteen dogs were randomly divided into four groups: PTH + BMSCs–scaffold, BMSCs–scaffold, total meniscectomy, and sham operation. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross, histological, and immunohistochemical analysis at 12 weeks postoperatively.
Results
In vitro study showed that the glycosaminoglycan (GAG)/DNA ratio and the expression of collagen type II (Col2) were significantly higher on day 21 as compared to the other time points. In vivo study showed that, compared with the BMSCs–scaffold group, the PTH + BMSCs–scaffold group showed better regeneration of the implanted tissue and greater similarity to native meniscus with respect to gross appearance, cells composition, and cartilage extracellular matrix deposition. This group also showed less expression of terminal differentiation markers of BMSC chondrogenesis as well as lower cartilage degeneration with less damage on the knee cartilage surface, higher expression of Col2 and lower expression of degeneration markers.
Conclusions
Our results demonstrated that PTH (1–34) promotes the regenerative and chondroprotective effects of the BMSCs–3D printed meniscal scaffold in a canine model, and thus their combination could be a promising strategy for meniscus tissue engineering.
MicroRNA-520a discourages lung cancer pathogenesis and progression involving the downregulation of RRM2 and Wnt signaling deficits
Authors: Xie Yi , Xue Congyu , Guo Shuai , Yang Lei
Published: May 2020

Background

Increasingly evidence has noted the critical functions of microRNAs (miRNAs) in disease control including cancer progression. This paper aimed to explore the functions of miR-520a in lung cancer (LC) and the downstream molecules implicated.
Methods

Aberrantly expressed miRNAs in LC tissues were screened out by miRNA microarrays. miR-520a expression in LC tissues and cell lines was determined, and the correlation between miR-520a level and survival rate of patients was analyzed. Altered expression of miR-520a was introduced to evaluate its function in LC cell malignant behaviors. The target mRNA and the potential signaling pathway mediated by miR-520a were figured out. Xenograft tumors were induced in mice to test the role of miR-520a in tumorigenesis in vivo.
Results

Poor expression of miR-520a was found in LC tissues and cell lines. A higher miR-520a level indicated a better survival rate in LC patients. Overexpression of miR-520a led to declines in cell viability, proliferation, migration, invasion and resistance to apoptosis. The target mRNAs of miR-520a were enriched on the Wnt signaling. miR-520a inactivated the Wnt pathway. miR-520a could bind to RRM2 and downregulate RRM2 expression in LC cells. Overexpression of RRM2 promoted the malignant behaviors of cancer cells, but this promotion was inhibited by miR-520a. Overexpression of miR-520a also inhibited the tumor growth and metastasis in nude mice.
Conclusion

The present study provided evidence that miR-520a could inhibit LC progression through RRM2 down-regulation and Wnt signaling deficit. This paper may offer novel ideas concerning LC treatment.
A GIS-based spatial correlation analysis for ambient air pollution and AECOPD hospitalizations in Jinhua, China
Authors: Du Wenjun , Zhang Weidong , Hu Hongyu , Zhang Miaoyun , He Yiling , Li Zhiming
Published: May 2020

The authors have removed this preprint from Research Square.
Physical geography shapes the distribution characteristics of extracellular polymeric substances in periphytic biofilms
Authors: Sun Pengfei , Xu Ying , Sun Rui , Gao Mengning , Wu Yonghong , Dolfing Jan
Published: May 2020

Background: Extracellular polymeric substances (EPS) are the glue that holds periphytic biofilms together. However, little is known about the chemical composition of the EPS and whether and if so how these components vary over different geographic regions. Therefore, we collected a large series of periphytic biofilms from paddy fields in different geographic regions to study the content, geographical distribution, and potential ecological function of EPS in periphytic biofilms, as well as the function of microbial components on EPS in periphytic biofilm.Results: EPS accounted for 1.3-2.9% of the total biomass of periphytic biofilms, while the protein content in periphytic biofilm was 1.8 to 20 times higher than that of the polysaccharides. The geographical distribution of EPS in periphytic biofilms follows the typical latitudinal diversity gradient theory: EPS contents decreased with increasing latitudes, but the ratio of protein to polysaccharide in periphytic biofilms showed the opposite trend. Physical geography characteristics, including temperature and light, are the principal forces driving the geographical distribution of EPS in periphytic biofilms, affecting their microbial composition. Prokaryotes in periphytic biofilm negatively affect the EPS content in periphytic biofilm, suggesting that prokaryotes may function as EPS consumers, while eukaryotes may be EPS producers, because they positively affect the EPS content in periphytic biofilm. Functionally, EPS components contribute to N and P accumulation in periphytic biofilms, as well as enhance the total organic carbon content in periphytic biofilm.Conclusion: These analyses provide invaluable information on the biogeochemistry of EPS in periphytic biofilms and their potential role in modulating nutrient cycles in paddy fields.
A proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients
Authors: Tobieson Lovisa , Czifra Zita , Wåhlén Karin , Marklund Niklas , Ghafouri Bijar
Published: May 2020

Background:
Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue.
Methods:
In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal.
Results:
We found unique protein patterns for each of the three compartments, particularly in the molecular weight range of 10–35 kDa.
Conclusion:
This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.
Comparison of Health Care Utilization Among Patients Affiliated and Not Affiliated with Healthcare Professionals in China
Authors: Si Yafei , Zhou Zhongliang , Su Min , Hu Han , Yang Zesen , Chen Xi
Published: May 2020

Background: Doing “more” in healthcare can be a major threat to the delivery of high-quality health care. It is important to identify the supplier-induced demand of healthcare. This study aims to test supplier-induced demand theory by comparing health care utilization among patients affiliated with healthcare professionals and their counterpart patients not affiliated with healthcare professionals.Methods: Using cross-sectional data of the China Labour-force Dynamics Survey (CLDS) implemented in 2014, we identified 806 patients affiliated with healthcare professionals and 22788 patients not affiliated with healthcare professionals. We used the coarsened exact matching method to control for confounding factors. The main outcomes were outpatient rate and expenditure as well as inpatient rate and expenditure.Results: The matched outpatient rate of patients not affiliated with healthcare professionals was 0.6% higher (P = .75) than that of their counterparts, and the matched inpatient rate was 1.1% lower (P = .17). Patients not affiliated with healthcare professionals paid significantly more (680 CNY, P < .001) than their counterpart patients did per outpatient visit (1126 CNY [95% CI 885–1368] VS 446 CNY [95% CI 248–643]), while they paid 2,061 CNY insignificant less per inpatient visit (P = .75).Conclusion: Our results lend support on supplier-induced demand hypothesis and highlight the need for policies to address the large outpatient care expenses of patients not affiliated with healthcare professionals. Creating incentives for providers to offer less avoidable healthcare service during outpatient visits may work to reduce healthcare costs.
Dynamic characteristics of a gear system with double-teeth spalling fault and its fault feature analysis
Authors: Shi Luojie , Wen Juan , Pan Baisong , Xiang Yongyong , Zhang Qi , Lin Congkai
Published: May 2020

Gear fault diagnosis has been a vital technology to enhance the reliability and reduce the maintenance cost of gear systems. Tooth spalling is one of the most destructive surface failure models of the gear faults. Revealing the dynamic characteristics of a gear system with spalling fault and extracting the fault feature are the premise and basis for effective fault diagnosis. Previous studies have mainly concentrated on the spalling damage on a single gear tooth, but the spalling distributed over double teeth which usually occurs in practical engineering problems is rarely reported. To remedy this deficiency, this paper constructs a new dynamical model of a gear system with double-teeth spalling fault and validates this model with various experimental tests. The dynamic characteristics of gear systems are obtained by considering the excitations induced by the number of spalling teeth, the relative position of two faulty teeth, and the rotational speed. The method based on the Variational Mode Decomposition (VMD) and the Fast Kurtogram (FK) is proposed to extract the features of the double-teeth spalling fault. First, the raw signal is decomposed into a set of Intrinsic Mode Functions (IMFs) by applying the VMD, and the IMFs with strong correlation are summed as a reconstructed signal. The reconstructed signal is then filtered by an optimal band-pass filter based on the FK. Combined with envelope spectrum analysis, the feature extraction ability of the proposed method is compared with that of the original FK method and the method based on the Empirical Mode Decomposition and the FK, respectively. The results indicate that the proposed dynamic model and fault feature extraction method can provide a theoretical basis for spalling defect diagnosis of gear systems.