bluuebunny/crossref_metadata_2025 huggingface dataset:
A strategic tourism marketing framework for sports mega events: The case of Athens Classic (Authentic) Marathon
Authors: Zouni Georgia , Markogiannaki Popi , Georgaki Ioanna
Published: January 2020

The purpose of this study is to examine the relationship between destination image, event image and satisfaction in the context of a mega event, the 34 Authentic Marathon of Athens (Greece). In particular, the present study investigates whether (a) the evaluation of the destination influences positively the level of satisfaction and intention to revisit the destination, (b) the evaluation of the event influences positively the level of satisfaction and intention to revisit the destination and (c) the level of satisfaction influences positively the intention to revisit the destination. A survey took place among sport tourists ( n = 241) during and after the end of the event. Results indicate that the evaluation of the event and of the destination is much related to the level of satisfaction. Moreover, the three variables (destination image, event image and satisfaction) are found to have a significant effect on the intention to revisit the destination.
Oral health status of children and adolescents with autism spectrum disorder: A systematic review of case-control studies and meta-analysis
Authors: Lam Phoebe PY , Du Rennan , Peng Simin , McGrath Colman PJ , Yiu Cynthia KY
Published: January 2020

Children and adolescents with autism spectrum disorder are thought to be more vulnerable to oral diseases than typically developing individuals due to cariogenic dietary habits, self-injurious behaviors, and increased barriers to dental care services. This review aimed to summarize current evidence comparing the oral health status of people diagnosed with and without autism spectrum disorder. Study selection and screening, data extraction, risk of bias assessment, and quality-of-evidence evaluation was conducted using the Grading of Recommendations Assessment Development and Evaluation approach and performed independently by two reviewers. A total of 16 studies were found eligible for qualitative synthesis and 15 were included in quantitative analysis. When comparing children and adolescents diagnosed with and without autism spectrum disorder, significantly higher prevalence of bruxism was identified. Individuals diagnosed with autism spectrum disorder were also found to have significantly lower salivary pH. However, no statistically significant differences in terms of caries prevalence and severity, oral hygiene and periodontal status, prevalence of malocclusion, dental traumatic injuries, as well as salivary flow rate and buffering capacity were found. The quality of evidence of each outcome was graded as very low mainly due to the overall high risk of bias, considerable heterogeneity, and imprecision.

Lay Abstract

Children and adolescents diagnosed with Autism Spectrum Disorder (ASD) are thought to be more vulnerable to oral diseases than typically-developing individuals. This is due to their increased barriers to dental care services, self-harm behaviors and dietary habits that may favor tooth decay. In this review, we summarized the current evidence comparing the oral health status of children and adolescents diagnosed with and without ASD. After a systematic search in the literature, we found that the salivary pH of individuals diagnosed with ASD was significantly lower, but the results were not clinically significant that can increase their risks to tooth decay. We also found weak evidence suggesting a higher percentage of children and adolescents diagnosed with ASD having the habit of tooth grinding compared with their neurotypical counterparts. When comparing salivary flow rate, tooth decay, gum diseases, tooth malalignment and tooth trauma; no significant differences were found between the two groups. The findings did not suggest ASD as a predisposing factor to oral diseases: other factors including sugary diet and inadequate oral hygiene may play a more important role. We also call for further research to establish more concrete association between ASD and oral diseases.
Endovascular coil embolization of proximal middle cerebral artery aneurysms has better outcomes than other middle cerebral artery aneurysms: A retrospective study
Authors: Sato Hirotaka , Haraguchi Koichi , Takahashi Yasuhiro , Ohtaki Shunya , Shimizu Tadakazu , Matsuura Nobuyuki , Ogane Kazumi , Ito Takeo
Published: January 2020

Purpose

Although some authors proposed that coil embolization in middle cerebral artery (MCA) aneurysms is a useful and effective alternative, the characteristics of the aneurysms may be different at each location. We compared the results of coil embolization of proximal middle cerebral artery aneurysms with those of other middle cerebral artery aneurysms.

Methods

Data from 46 patients with 50 aneurysms were retrospectively evaluated. We defined the aneurysms inside of the insular cortex as proximal MCA (pMCA) aneurysms and those outside of the insular cortex as non-proximal MCA (npMCA) aneurysms. The results of the occlusion were divided into classes 1, 2, and 3 of the Raymond scale. We collected the results of the occlusion from the operative notes supplied by a neuroendovascular specialist.

Results

Univariate analysis identified favorable results for pMCA aneurysms (class 1: pMCA = 22 npMCA = 11; P < 0.01). In the radiological follow-up results, we achieved class 1 in 29 patients (69%; pMCA = 21 and npMCA = 8; P < 0.01). Side wall type aneurysms (pMCA = 14, npMCA = 2; P < 0.01) and the number of branches from the neck of ≤1 (pMCA = 14, npMCA = 2; P < 0.01) were significantly recognized at the pMCA.

Conclusions

Proximal middle cerebral artery aneurysm clipping is difficult because the origin of the lenticulostriate arteries is often hidden behind the aneurysmal dome. In the present study, endovascular coil embolization for pMCA aneurysms obtained better results than that for npMCA aneurysms because of the morphological characteristics. Endovascular coil embolization seems to be efficacious for pMCA aneurysms as compared with npMCA aneurysms.
Wear optimization of titanium alloy cutter milled with microtextured ball-end milling cutter
Authors: Zhang Yuhua , Ji Hongzhi
Published: January 2020

Aimed at solving the problems of tool wear and poor surface quality in milling a Ti alloy with a ball-end milling cutter, a method of applying a microtexture to a tool rake face to reduce tool wear is proposed in this article. By comparing the wear morphology of microtextured tools with that of nontextured tools after milling with the same stroke, the antifriction and antiwear mechanism of the micropit texture and the failure mode of the ball-end milling cutter are analyzed. The results of a simulation and orthogonal experiments reveal that with the increase of the micropit parameters, the wear value of the rake and rear faces first decreases and then increases. The effects of the micropit parameters on the wear value of the ball-end milling cutter decrease in the following order: distance from edge > diameter > spacing > depth. Finally, by using a multi-objective optimization method, the optimal solution set of the texture parameters of micropits is obtained by evaluating the wear values of the rake and rear faces of the ball-end milling cutters: 46 μm < diameter < 50 μm, 23 μm < depth < 26 μm, 109 μm < spacing < 112 μm, and 85 μm < distance from edge < 89 μm.
Multivariable nonlinear predictive control of a clinker sintering system at different working states by combining artificial neural network and autoregressive exogenous
Authors: Wang Meiqi , Chen Enli , Liu Pengfei , Guo Wenwu
Published: January 2020

The clinker sintering system is widely controlled manually in the factory, and there is a large divergence between a linearized control model and the nonlinear rotary kiln system, so the controlled variables cannot be calculated accurately. To accommodate the multivariable and nonlinear features of cement clinker sintering systems, steady-state model and dynamic models are established using extreme learning machine and autoregressive exogenous models. The steady-state model is used to describe steady-state nonlinear relations, and the dynamic model is used to describe the dynamic characteristics of the sintering system. By obtaining the system gains based on the steady-state model, the parameters of the dynamic model are rectified online to conform to the system gain. Thus, a dynamic model named extreme learning machine-autoregressive exogenous is proposed, which can describe the nonlinear dynamic features of a sintering system. The results show that, compared with the autoregressive exogenous model, the extreme learning machine-autoregressive exogenous model has good control performance on the multivariable and nonlinear system and can reduce computing resource requirements during the online running. In addition, fluctuations of NOx and O2 concentrations decreases, again demonstrating good control performance of an actual clinker sintering system using the extreme learning machine-autoregressive exogenous model.
Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis
Authors: Kelly Dearbhla M , Rothwell Peter M
Published: January 2020

Background

Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined.

Aim

We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure.

Summary of review

We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria ± glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle–Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63–2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51–1.95; p < 0.001), albeit with considerable heterogeneity between studies (p < 0.001; I2 = 77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39–2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13–2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33–2.14; p < 0.001).

Conclusions

Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.
Inconclusive evidence for the efficacy of tranexamic acid in reducing transfusions, postoperative infection or hematoma formation after primary shoulder arthroplasty: A meta-analysis with trial sequential analysis
Authors: Rojas Jorge , Srikumaran Uma , McFarland Edward G
Published: January 2020

Background

Tranexamic acid efficacy on clinically relevant adverse outcomes in patients undergoing shoulder arthroplasty has been contradictory. The aim of this review was to analyze whether tranexamic acid administration could decrease transfusions, infection and hematoma formation in patients undergoing shoulder arthroplasty.

Methods

PubMed, EMBASE, and the Cochrane Library were searched up to May 2019 for randomized controlled trials comparing tranexamic acid to placebo in shoulder arthroplasty. Random-effect models were performed to meta-analyze the evidence. Trial sequential analysis was used to calculate and to establish the conclusiveness of the evidence derived from the meta-analysis.

Results

Four randomized controlled trials comprising 375 patients were included. Meta-analysis showed no effect of tranexamic acid on transfusion rate (RR = 0.48 (adjusted 95% CI 0.05 to 3.85)). The possible effect of tranexamic acid on hematoma formation or infection rates after shoulder arthroplasty is non-estimable with the current evidence. The sample size necessary to reliably determine if tranexamic acid decreases transfusions, infection rates and hematoma formation is not available from the current literature as determined by the trial sequential analysis.

Discussion

While tranexamic acid has proven its efficacy in decreasing blood loss in shoulder arthroplasty, this meta-analysis of randomized controlled trials clarifies that there is currently no conclusive evidence for a positive effect of tranexamic acid upon transfusion rate, infection rates or hematoma formation in patients undergoing primary shoulder arthroplasty.
Effect of glenoid perforation during total shoulder arthroplasty on glenoid component cement fixation and suprascapular nerve
Authors: Pace Gregory I , Thomas Rachel A , Zale Connor L , Lewis Gregory S , Kim Raymond Y , Kim H Mike
Published: January 2020

Background

Arthritic glenoids are susceptible to vault perforation during total shoulder arthroplasty. We investigated the effects of glenoid perforation and subsequent cement extrusion on the suprascapular nerve and on the glenoid cement infiltration.

Methods

Total shoulder arthroplasty using three-pegged glenoid components were performed on 10 cadaveric shoulders assigned to two groups (perforation vs. control). In perforation group, the glenoids were reamed eccentrically and intentionally perforated medially through the central peg hole, whereas control group received perpendicular reaming with no perforation. Bone cement was applied to each peg. Spatial relationship between the extruded cement and the suprascapular nerve, and the amount of cement infiltration into the cancellous bone were evaluated.

Results

In perforation group, five specimens were perforated anteriorly, and two posteriorly. In the two posteriorly perforated specimens, the suprascapular nerve was in direct contact with extruded cement at the spinoglenoid notch. Perforation group showed significantly less cement infiltration into the cancellous bone than control group ( p = 0.008).

Conclusions

Glenoid perforation decreases the volume of cement infiltration into the cancellous bone potentially compromising glenoid component fixation. Glenoid perforation tends to occur anteriorly rather than posteriorly in arthritic glenoids; however, if perforation occurs posteriorly, the suprascapular nerve is at immediate risk from the extruded cement. Level of evidence: Basic science study.
Continuous Glucose Monitoring Devices: Past, Present, and Future Focus on the History and Evolution of Technological Innovation
Authors: Didyuk Olesya , Econom Nicolas , Guardia Angelica , Livingston Kelsey , Klueh Ulrike
Published: January 2020

The concept of implantable glucose sensors has been promulgated for more than 40 years. It is now accepted that continuous glucose monitoring (CGM) increases quality of life by allowing informed diabetes management decisions as a result of more optimized glucose control. The focus of this article is to provide a brief overview of the CGM market history, emerging technologies, and the foreseeable challenges for the next CGM generations as well as proposing possible solutions in an effort to advance the next generation of implantable sensor.
Anticolon Cancer Potential of (2Z)-2-[(4′-Hydroxyphenyl) Methylene]-6-Methoxy-7-Prenyl-3(2H)-Benzofurane, a New Aurone From Psoralea corylifolia
Authors: Liu Ai-Hua , Liu Li-Hua , Liu Chun-Ying
Published: January 2020

A new aurone, (2 Z)-2-[(4′-hydroxyphenyl) methylene]-6-methoxy-7-prenyl-3(2 H)-benzofurane (1), together with 6 known compounds (2-7), was isolated from the EtOAc-soluble extract of the seeds of Psoralea corylifolia. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for in vitro inhibitory activity against a human colon cancer cell line (SW620). Compounds 1 to 3 showed moderate cytotoxicity against the SW620 cells with IC50 values ranging from 24.31 to 28.72 μM. Among these compounds, 1 showed higher cytotoxicity against SW620 cells with an IC50 value of 24.31 μM.
Antioxidant, Anti-inflammatory, and Antiproliferative Activity of Mori Cortex Radicis Extracts
Authors: Bayazid Al B. , Kim Jae G. , Park Seo H. , Lim Beong O.
Published: January 2020

Mori Cortex Radicis (MCR) is a well-known Korean and Chinese folk medicine with anti-obesity, anti-inflammatory, anti-asthmatic, and hypoglycemic activities. This study was aimed to evaluate the total phenolic and flavonoid contents, as well as intracellular antioxidant and anti-inflammatory effects of water and 70% (v/v) ethanol extracts of MCR. The antioxidant activities of MCR extracts were determined with diphenyl-2-picrylhydrazyl and 2,2′-azinobis[3-ethylbenzothiazoline-6-sulfonic] scavenging activity assays. The suppressive activities of MCR extracts on the production of nitric oxide (NO*) and the expression of cytokines, c-Fos, activated p38-Mitogen-activated protein kinase (MAPK), and Nuclear factor Kappa B (NF-κB) and splenocytes proliferation in lipopolysaccharide-treated macrophages were determined. Furthermore, this study demonstrated the effects of MCR on reactive oxygen species production in murine macrophages. Mori Cortex Radicis restored deoxyribonucleic acid damages at higher concentrations of the extracts and significantly suppressed free radicals and NO* production. In this study, MCR significantly restored inflammatory responses and intracellular antioxidant activities in murine macrophages (RAW 264.7), which anticipated that MCR could be used as a natural anti-inflammatory agent.
The Effect of Optical Flow Motion Direction on Vection Strength
Authors: Fujii Yoshitaka , Seno Takeharu
Published: January 2020

In some phenomena of visual perception, the motion direction of visual stimuli can affect perception. In particular, asymmetries between oblique directions and cardinal (horizontal and vertical) directions have been reported and are known as oblique effects (e.g., contrast sensitivity and motion threshold). In this study, we investigated how vection strength depends on motion direction. Participants observed random-dot optical flow in a circular field and rated the perceived vection strength. Dot movement was systematically controlled using the following angles: 0° (up), 30°, 45°, 60°, 90°, 120°, 135°, 150°, and 180° (down). We found that vection strength depended on motion direction and was weaker in the oblique directions than cardinal directions. Thus, the effect of motion direction on vection strength was variable, as seen in the shape of the oblique effect.
Day case primary trans-urethral resection of bladder tumour (TURBT) as standard in a single UK centre. Should this be the new norm?
Authors: Austin Tomas , Robinson Richard , Wilby Daniel , Hall Stuart , Hodgson Dominic
Published: January 2020

Objectives:

A retrospective study was conducted to examine the feasibility and safety of performing trans-urethral resection of bladder tumour (TURBT) in newly diagnosed patients as a day case operation.

Patients and methods:

All patients who underwent a primary TURBT over a 12 month period were included. Data were collected on patient demographics, tumour characteristics, day case vs. inpatient admission, indications for inpatient admission, re-admission rates within 28 days, and surrogate markers for quality of resection including recurrence rates.

Results:

A total of 172 patients were included. TURBT was performed as a day case procedure on 138 patients (80.2%). Rates of re-admission within 28 days were 7.2% and 5.9% in the day case and inpatient cohorts respectively. One hundred and thirty (75.6%) patients had non-muscle invasive bladder cancer (NMIBC). Of these, 84 (64.6%) were found to have detrusor muscle in their specimens, and 86 (66.2%) received peri-operative mitomycin C. Twelve month recurrence rates were 12%, 27% and 33% for low, intermediate and high-risk NMIBC respectively.

Conclusion:

This study shows that day case surgery for TURBT is feasible in the majority of patients, with a low rate of re-admission. Our data suggest that day case TURBT is suitable as standard practice in our institution and should be considered by others.

Level of evidence:

2b.
Could superior capsule findings be used as a predictor for partial bursal-sided rotator cuff tears?
Authors: Kanatlı Ulunay , Ayanoglu Tacettin , Esen Erdinc , Ataoglu Baybars , Ozer Mustafa , Cetinkaya Mehmet , Kaptan Ahmet Yigit
Published: January 2020

Purpose:

The purpose of this study was to investigate the relationship between the superior capsule tear patterns and synovitis with subacromial pathologies, such as bursal-sided rotator cuff tear and subacromial impingement syndrome.

Methods:

Fifty patients who underwent arthroscopic treatment for isolated bursal-sided tear were included in the study. Fifty more patients who underwent arthroscopic treatment for isolated Superior Labrum Anterior Posterior (SLAP) 2 lesion without pathology in the rotator cuff were included in the control group. Firstly, superior capsule tear and common synovitis on the rotator cable were assessed during glenohumeral joint examination. Coracoacromial Ligament (CAL) degeneration grading was performed according to the Royal Berkshire Hospital classification. Bursal-sided partial tear grading was done using Ellman classification. Whether or not there was a relationship between synovitis, classic capsule tear, plus reverse flap capsule tear, and partial bursal-sided tear existence.

Results:

There were 21 patients with reverse flap capsule tear in the study group and 3 patients in the control group. In addition, there were 13 patients with synovitis in the study group and 4 in the control group. Compared to the control group, there was also a significant positive correlation in the presence of both synovitis and reverse flap capsule tear with the presence of bursal-sided tear in the study group ( p = 0.000). There was, however, no significant difference between the presence of classical capsule tear and the presence of bursal-sided tear ( p = 0.485).

Conclusion:

This study shows that the presence of reverse flap capsule tear and synovitis was associated with partial bursal-sided tears. Therefore, if the reverse flap capsule tear or synovitis is detected in the superior capsule, the rotator cuff should be evaluated in more detail during subacromial bursoscopy in order not to miss a bursal-sided partial cuff tear.
Establishing an Anal Cancer Screening Program in an Outpatient HIV Clinic: Referral Patterns and Patient Perceptions Survey
Authors: Sowah Leonard A. , Schmalzle Sarah A. , Khambaty Mariam , Buchwald Ulrike K.
Published: January 2020

People living with HIV are at high risk for anal cancer (AC); however, the impact of screening for and treatment of precancerous anal lesions on AC incidence remains uncertain. In 2013, we conducted a survey of HIV providers evaluating the perceived need for an institutional AC screening program. Based on an overwhelmingly positive response, we established a dedicated AC screening clinic (including provision of high-resolution anoscopies) embedded within the institutional HIV clinic. Here, we describe that referral of high-risk patients in the first 3 years was lower than expected. Referral patterns suggest that screening practices vary widely among HIV providers within the institution. Anal cancer clinic patients who completed a perception survey rated the value of AC screening as high, with perceived positive health impact, and identified their providers as the main source of information on AC and AC screening. Our findings imply remaining provider-related barriers to AC screening.
Benefits of Beamforming With Local Spatial-Cue Preservation for Speech Localization and Segregation
Authors: Wang Le , Best Virginia , Shinn-Cunningham Barbara G.
Published: January 2020

A study was conducted to examine the benefits afforded by a signal-processing strategy that imposes the binaural cues present in a natural signal, calculated locally in time and frequency, on the output of a beamforming microphone array. Such a strategy has the potential to combine the signal-to-noise ratio advantage of beamforming with the perceptual benefit of spatialization to enhance performance in multitalker mixtures. Participants with normal hearing and with hearing loss were tested on both speech localization and speech-on-speech masking tasks. Performance for the spatialized beamformer was compared with that for three other conditions: a reference condition with no processing, a beamformer with no spatialization, and a hybrid beamformer that operates only in the high frequencies to preserve natural binaural cues in the low frequencies. Beamforming with full-bandwidth spatialization supported speech localization and produced better speech reception thresholds than the other conditions.
Deportations Near the Schoolyard: Examining Immigration Enforcement and Racial/Ethnic Gaps in Educational Outcomes
Authors: Kirksey J. Jacob , Sattin-Bajaj Carolyn , Gottfried Michael A. , Freeman Jennifer , Ozuna Christopher S.
Published: January 2020

With increased tensions and political rhetoric surrounding immigration enforcement in the United States, schools are facing greater challenges in ensuring support for their students of immigrant and Latino/a origin. This study examined the associations between deportations near school districts and racial/ethnic gaps in educational outcomes in school districts across the country. With data from the Stanford Educational Data Archive, the Civil Rights Data Collection, and the Transactional Records Access Clearinghouse, this study used longitudinal, cross-sectional analyses and found that in the years when districts had more deportations occurring within 25 miles, White-Latino/a gaps were larger in math achievement and rates of chronic absenteeism. No associations were found for gaps in English language arts achievement or rates of bullying. Implications for researchers, policymakers, and school leaders are discussed.
Increased Cortical Thickness in Patients With Major Depressive Disorder Following Antidepressant Treatment
Authors: Nemati Samaneh , Abdallah Chadi G.
Published: January 2020

Background

Considering the slow-acting properties of traditional antidepressants, an important challenge in the field is the identification of early treatment response biomarkers. Reduced cortical thickness has been reported in neuroimaging studies of depression. However, little is known whether antidepressants reverse this abnormality. In this brief report, we investigated early cortical thickness changes following treatment with sertraline compared to placebo.

Methods

Participants (n = 215) with major depressive disorder were randomized to a selective serotonin reuptake inhibitor, sertraline, or to placebo. Structural magnetic resonance imaging scans were acquired at baseline and one week following treatment. Response was defined as at least 50% improvement in Hamilton rating scale for depression score at week 8. In a vertex-wise approach, we examined the effects of treatment, response, and treatment × response.

Results

Following correction for multiple comparisons, we found a significant effect of treatment, with widespread increase in cortical thickness following sertraline compared to placebo. Clusters with increased thickness were found in the left medial prefrontal cortex, right medial and lateral prefrontal cortex, and within the right parieto-temporal lobes. There were no sertraline-induced cortical thinning, and no significant response effects or treatment × response interactions.

Conclusion

Our findings suggest that cortical thickness abnormalities may be responsive to antidepressant treatment. However, a relationship between these early cortical changes and later treatment response was not demonstrated. Future studies would be needed to investigate whether those early effects are maintained at eight weeks and are associated with enhanced response.
Operative Approaches to Ankle and Hindfoot Arthroscopy
Authors: Carreira Dominic S. , Garden Steven R. , Ueland Thomas
Published: January 2020

The role of arthroscopy in the management of ankle and hindfoot pathology management has increased greatly in recent years with the potential for lower complication rates, faster recovery, improved access, and improved outcomes when compared to open techniques. Procedural variations exist as techniques aim to optimize lesion access, decrease operative time, and improve patient safety. Our goal is to summarize the described approaches and patient positionings common in minimally invasive arthroscopic surgery for anterior, lateral, and posterior ankle pathologies. A survey of pathology organized by arthroscopic approach and a review of recent advances in concomitant lesion management may be useful when planning arthroscopic foot and ankle surgery.

Level of Evidence:

Level V, expert opinion.
Association of Preoperative Opioid Use and Prolonged Postoperative Opioid Use Following Total Ankle Arthroplasty
Authors: DeMik David E. , Cychosz Chris C. , Bedard Nicholas A. , Barton Cameron , An Qiang , Duchman Kyle R.
Published: January 2020

Background:

Perioperative opioid consumption has received a great deal of recent attention. However, perioperative opioid utilization in the total ankle arthroplasty (TAA) population has not been well studied. We sought to identify factors associated with postoperative opioid use following TAA.

Methods:

The PearlDiver Research Program was used to query the Humana, Inc, administrative claims database from 2007 to 2017 for patients undergoing TAA. Additional variables of interest were identified using ICD-9 and ICD-10 codes. Preoperative opioid use was defined as having filled an opioid prescription in the 3 months before TAA. Prescription opioid claims data were tracked for 12 months postoperatively. Risk ratios (RRs) were calculated and multivariate analysis was performed at 3, 6, and 12 months postoperatively.

Results:

A total of 544 patients who underwent TAA were identified, with 180 (33.1%) filling an opioid prescription preoperatively. Those filling prescriptions preoperatively had a significantly greater risk for postoperative opioid use compared to those not taking opioids (RR: 4.36 [95% confidence interval (CI): 2.80-6.80] at 12 months). Anxiety or depression (RR: 2.27 [1.44-3.59]), low back pain (LBP) (RR: 2.27 [1.50-3.42]), and fibromyalgia (RR: 2.15 [1.42-3.28]) were also found to increase the risk of taking opioids at 12 months postoperatively. Multivariate analysis found preoperative opioid use to be the strongest predictor of postoperative opioid use.

Conclusions:

Nearly one-third of patients filled an opioid prescription within 3 months of TAA, and filling a prescription preoperatively was the strongest factor associated with postoperative opioid use. Fibromyalgia, depression or anxiety, and LBP were also associated with an increased likelihood of postoperative opioid use.

Level of Evidence:

Level III, retrospective cohort study.
Dnmt3a loss and Idh2 neomorphic mutations mutually potentiate malignant hematopoiesis
Authors: Zhang Xiaotian , Wang Xinyu , Wang Xue Qing David , Su Jianzhong , Putluri Nagireddy , Zhou Ting , Qu Ying , Jeong Mira , Guzman Anna , Rosas Carina , Huang Yun , Sreekumar Arun , Li Wei , Goodell Margaret A.
Published: January 2020

Mutations in the epigenetic regulators DNMT3A and IDH1/2 co-occur in patients with acute myeloid leukemia and lymphoma. In this study, these 2 epigenetic mutations cooperated to induce leukemia. Leukemia-initiating cells from Dnmt3a−/− mice that express an IDH2 neomorphic mutant have a megakaryocyte-erythroid progenitor–like immunophenotype, activate a stem-cell–like gene signature, and repress differentiated progenitor genes. We observed an epigenomic dysregulation with the gain of repressive H3K9 trimethylation and loss of H3K9 acetylation in diseased mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). HDAC inhibitors rapidly reversed the H3K9 methylation/acetylation imbalance in diseased mouse HSPCs while reducing the leukemia burden. In addition, using targeted metabolomic profiling for the first time in mouse leukemia models, we also showed that prostaglandin E2 is overproduced in double-mutant HSPCs, rendering them sensitive to prostaglandin synthesis inhibition. These data revealed that Dnmt3a and Idh2 mutations are synergistic events in leukemogenesis and that HSPCs carrying both mutations are sensitive to induced differentiation by the inhibition of both prostaglandin synthesis and HDAC, which may reveal new therapeutic opportunities for patients carrying IDH1/2 mutations.
von Willebrand factor binding to myosin assists in coagulation
Authors: Flood Veronica H. , Slobodianuk Tricia L. , Keesler Daniel , Lohmeier Hannah K. , Fahs Scot , Zhang Liyun , Simpson Pippa , Montgomery Robert R.
Published: January 2020

von Willebrand factor (VWF) binds to platelets and collagen as a means of facilitating coagulation at sites of injury. Recent evidence has shown that myosin can serve as a surface for thrombin generation and binds to activated factor V and factor X. We studied whether VWF can also bind myosin as a means of bringing factor VIII (FVIII) to sites of clot formation. A myosin-binding assay was developed using skeletal muscle myosin to measure VWF binding, and plasma-derived and recombinant VWF containing molecular disruptions at key VWF sites were tested. Competition assays were performed using anti-VWF antibodies. FVIII binding to myosin was measured using a chromogenic FVIII substrate. Thrombin generation was measured using a fluorogenic substrate with and without myosin. Wild-type recombinant VWF and human plasma VWF from healthy controls bound myosin, whereas plasma lacking VWF exhibited no detectable myosin binding. Binding was multimer dependent and blocked by anti-VWF A1 domain antibodies or A1 domain VWF variants. The specific residues involved in myosin binding were similar, but not identical, to those required for collagen IV binding. FVIII did not bind myosin directly, but FVIII activity was detected when VWF and FVIII were bound to myosin. Myosin enhanced thrombin generation in platelet-poor plasma, although no difference was detected with the addition of myosin to platelet-rich plasma. Myosin may help to facilitate delivery of FVIII to sites of injury and indirectly accelerate thrombin generation by providing a surface for VWF binding in the setting of trauma and myosin exposure.
Undetectable peripheral blood MRD should be the goal of venetoclax in CLL, but attainment plateaus after 24 months
Authors: Lew Thomas E. , Anderson Mary Ann , Lin Victor S. , Handunnetti Sasanka M. , Came Neil A. , Blombery Piers , Westerman David A. , Wall Meaghan , Tam Constantine S. , Roberts Andrew W. , Seymour John F.
Published: January 2020

The highly selective BCL2 inhibitor venetoclax achieves deep responses in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including undetectable minimal residual disease (uMRD). We retrospectively reviewed 62 patients with CLL treated with venetoclax to investigate the performance of peripheral blood (PB) compared with bone marrow (BM) assessment of MRD; the kinetics, clinicopathological associations, and longer-term outcomes of uMRD attainment and recrudescence; and the ability of venetoclax dose escalation to deepen responses. Among 16 patients who achieved PB uMRD and had contemporaneous BM assessments, 13 (81%) had confirmed BM uMRD, and patients with PB uMRD had outcomes at least as favorable as those with BM uMRD for time to progression, overall survival, and MRD recrudescence. Excluding 2 patients lacking earlier assessment, the median time to PB uMRD was 18 (range, 5-26) months, with 90% of instances achieved by 24 months. There was no new PB uMRD attainment after 24 months without treatment intensification. The dominant association with earlier attainment of uMRD was concurrent rituximab (P = .012). Complex karyotype was associated with inferior uMRD attainment after 12 months of therapy (P = .015), and patients attaining uMRD whose disease harbored TP53 abnormalities demonstrated a trend toward earlier recrudescence (P = .089). Of patients who received venetoclax dose escalations, 4 (27%) of 15 achieved improvements in response. For patients with R/R CLL receiving venetoclax, PB uMRD commonly correlates with BM uMRD and is associated with a comparable longer-term prognosis. Concurrent rituximab augments uMRD attainment, but dose escalation and further treatment beyond 24 months infrequently deepen responses.
Automatic construction of metabolic models with enzyme constraints
Authors: Bekiaris Pavlos Stephanos , Klamt Steffen
Published: January 2020

Background

In order to improve the accuracy of constraint-based metabolic models, several approaches have been developed which intend to integrate additional biological information. Two of these methods, MOMENT and GECKO, incorporate enzymatic (kcat) parameters and enzyme mass constraints to further constrain the space of feasible metabolic flux distributions. While both methods have been proven to deliver useful extensions of metabolic models, they may considerably increase size and complexity of the models and there is currently no tool available to fully automate generation and calibration of such enzyme-constrained models from given stoichiometric models.

Results

In this work we present three major developments. We first conceived short MOMENT (sMOMENT), a simplified version of the MOMENT approach, which yields the same predictions as MOMENT but requires significantly fewer variables and enables direct inclusion of the relevant enzyme constraints in the standard representation of a constraint-based model. When measurements of enzyme concentrations are available, these can be included as well leading in the extreme case, where all enzyme concentrations are known, to a model representation that is analogous to the GECKO approach. Second, we developed the AutoPACMEN toolbox which allows an almost fully automated creation of sMOMENT-enhanced stoichiometric metabolic models. In particular, this includes the automatic read-out and processing of relevant enzymatic data from different databases and the reconfiguration of the stoichiometric model with embedded enzymatic constraints. Additionally, tools have been developed to adjust (kcat and enzyme pool) parameters of sMOMENT models based on given flux data. We finally applied the new sMOMENT approach and the AutoPACMEN toolbox to generate an enzyme-constrained version of the E. coli genome-scale model iJO1366 and analyze its key properties and differences with the standard model. In particular, we show that the enzyme constraints improve flux predictions (e.g., explaining overflow metabolism and other metabolic switches) and demonstrate, for the first time, that these constraints can markedly change the spectrum of metabolic engineering strategies for different target products.

Conclusions

The methodological and tool developments presented herein pave the way for a simplified and routine construction and analysis of enzyme-constrained metabolic models.
Downregulation of lncRNA DANCR promotes osteogenic differentiation of periodontal ligament stem cells
Authors: Wang Zhuo , Huang Yuanliang , Tan Luanjun
Published: January 2020

Background

Long non-coding RNAs (lncRNAs) have been widely known to have an appreciable effect in physiology and pathology. In tooth regeneration, periodontal ligament stem cells (PDLSCs) are regarded as a key effector, whereas, how lncRNA acts in the osteogenic differentiation of PDLSCs have not been completely understood. This study aims to find out the relationship between lncRNA DANCR and the proliferation and osteogenic differentiation of PDLSCs.

Methods

Microarray was used to observe the different expression of lncRNAs in differentiated and undifferentiated PDLSCs. And then osteogenic-related lncRNA, DANCR was screened out. Its effects on proliferation and osteogenic differentiation was explored by constructing an overexpression and inhibition model. qRT-PCR was used to detect the mRNA expression of osteogenesis related genes. MTT assay was performed to assess the effects of DANCR on cell growth curve. To quantify the effects of DANCR on osteogenic differentiation of PDLSCs, ALP staining and alizarin red was performed in basic culture medium and osteogenic medium. Data were statistically processed.

Results

Compared with the undifferentiated PDLSCs, the alizarin red staining level was higher in differentiated PDLSCs. And the expressions of osteogenic differentiation marker genes Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein (BMP-2) were significantly increased in the differentiated PDLSCs. Furthermore, we noticed that comparing with control groups, the expression of lncRNA DANCR decreases markedly in osteogenically induced PDLSCs. DANCR promoted proliferation of PDLSCs, as evidenced by cell viability. Further investigation has proven that the downregulation of DANCR shows in the calcium sediment forming, alkaline phosphatase (ALP) activation and some osteogenic-related gene markers’ upregulation including Runx2, OCN and BMP-2, which finally results in the osteogenic differentiation of PDLSCs following the transfection and induction. Conversely, DANCR upregulation was shown to repress the osteogenic differentiation potential of PDLSCs.

Conclusions

The osteogenic differentiation of PDLSCs has proven to related to the down regulation of lncRNA DANCR. And this paper throws light on the effects of DANCR in the process of PDLSCs’ osteogenic differentiation.
Changes in life history traits and transcriptional regulation of Coccinellini ladybirds in using alternative prey
Authors: Chen Mei-Lan , Huang Yu-Hao , Qiu Bo-Yuan , Chen Pei-Tao , Du Xue-Yong , Li Hao-Sen , Pang Hong
Published: January 2020

Background

Ladybird beetles (Coleoptera, Coccinellidae) are highly diverse in their feeding habits. Most of them are specialist feeders, while some can have a broad spectrum of prey. As a representative group of generalists, the tribe Coccinellini includes many aphidophagous species, but members of this tribe also feed on other hemipterous insects including coccids, psyllids and whiteflies. As a result, several species are effective biological control agents or invasive species with serious non-target effects. Despite their economic importance, relatively little is known about how they adapt to new prey.

Results

In this study, comparisons of the life history traits and transcriptomes of ladybirds fed initial (aphids) and alternative prey (mealybugs) were performed in three Coccinellini species. The use of alternative prey greatly decreased performance, implied by the significantly prolonged development time and decreased survival rate and adult weight. Prey shifts resulted in a set of differentially expressed genes encoding chemosensory proteins and digestive and detoxifying enzymes.

Conclusions

Our results suggest that these generalists do not perform well when they use alternative prey as the sole nutrition source. Although their capacity for predation might have created an opportunity to use varied prey, they must adapt to physiological obstacles including chemosensing, digestion and detoxification in response to a prey shift. These findings challenge the effect of Coccinellini predators on the biological control of non-aphid pests and suggest the possibility of non-target attacks by so-called specialists.
miRNA and circRNA expression patterns in mouse brain during toxoplasmosis development
Authors: Zhou Chun-Xue , Ai Kang , Huang Cui-Qin , Guo Jing-Jing , Cong Hua , He Shen-Yi , Zhu Xing-Quan
Published: January 2020

Background

Increasing evidence has shown that circular RNAs (circRNAs) are involved in neurodegenerative disorders, but their roles in neurological toxoplasmosis are yet to know. This study examined miRNA and circRNA expressions in mouse brain following oral infection withT. gondiiPru strain.

Results

Total RNA extracted from acutely infected (11 days post infection (DPI)), chronically infected (35 DPI) and uninfected mouse brain samples were subjected to genome-wide small RNA sequencing. In the acutely infected mice, 9 circRNAs and 20 miRNAs were upregulated, whereas 67 circRNAs and 28 miRNAs were downregulated. In the chronically infected mice, 2 circRNAs and 42 miRNAs were upregulated, whereas 1 circRNA and 29 miRNAs were downregulated. Gene ontology analysis predicted that the host genes that produced the dysregulated circRNAs in the acutely infected brain were primarily involved in response to stimulus and ion binding activities. Furthermore, predictive interaction networks of circRNA-miRNA and miRNA-mRNA were constructed based on genome-wide transcriptome sequencing and computational analyses, which might suggest the putative functions of miRNAs and circRNAs as a large class of post-transcriptional regulators.

Conclusions

These findings will shed light on circRNA-miRNA interactions during the pathogenesis of toxoplasmosis, and they will lay solid foundation for studying the potential regulation roles of miRNAs and circRNAs inT. gondiiinduced pathogenesis.
Comparisons of microbiological characteristics and antibiotic resistance of Klebsiella pneumoniae isolates from urban rodents, shrews, and healthy people
Authors: Zhong Xue-shan , Li Yong-zhi , Ge Jing , Xiao Gang , Mo Yun , Wen Yu-qi , Liu Jing-ping , Xiong Yi-quan , Qiu Min , Huo Shu-ting , Cheng Ming-ji , Chen Qing
Published: January 2020

Background

The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people.

Results

K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum β-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult.

Conclusions

Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.