bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Reduced’ HUNT model outperforms NLST and NELSON study criteria in predicting lung cancer in the Danish screening trial
Authors: Røe Oluf Dimitri , Markaki Maria , Tsamardinos Ioannis , Lagani Vincenzo , Nguyen Olav Toai Duc , Pedersen Jesper Holst , Saghir Zaigham , Ashraf Haseem Gary
Published: November 2019

Hypothesis

We hypothesise that the validated HUNT Lung Cancer Risk Model would perform better than the NLST (USA) and the NELSON (Dutch‐Belgian) criteria in the Danish Lung Cancer Screening Trial (DLCST).

Methods

The DLCST measured only five out of the seven variables included in validated HUNT Lung Cancer Model. Therefore a ‘Reduced’ model was retrained in the Norwegian HUNT2-cohort using the same statistical methodology as in the original HUNT model but based only on age, pack years, smoking intensity, quit time and body mass index (BMI), adjusted for sex. The model was applied on the DLCST-cohort and contrasted against the NLST and NELSON criteria.

Results

Among the 4051 smokers in the DLCST with 10 years follow-up, median age was 57.6, BMI 24.75, pack years 33.8, cigarettes per day 20 and most were current smokers. For the same number of individuals selected for screening, the performance of the ‘Reduced’ HUNT was increased in all metrics compared with both the NLST and the NELSON criteria. In addition, to achieve the same sensitivity, one would need to screen fewer people by the ‘Reduced’ HUNT model versus using either the NLST or the NELSON criteria (709 vs 918, p=1.02e-11 and 1317 vs 1668, p=2.2e-16, respectively).

Conclusions

The ‘Reduced’ HUNT model is superior in predicting lung cancer to both the NLST and NELSON criteria in a cost-effective way. This study supports the use of the HUNT Lung Cancer Model for selection based on risk ranking rather than age, pack year and quit time cut-off values. When we know how to rank personal risk, it will be up to the medical community and lawmakers to decide which risk threshold will be set for screening.
Endoscopic mucosal resection is effective for laterally spreading lesions at the anorectal junction
Authors: Shahidi Neal , Sidhu Mayenaaz , Vosko Sergei , van Hattem W Arnout , Bar-Yishay Iddo , Schoeman Scott , Tate David J , Holt Bronte , Hourigan Luke F , Lee Eric YT , Burgess Nicholas G , Bourke Michael J
Published: November 2019

Objective

The optimal approach for removing large laterally spreading lesions at the anorectal junction (ARJ-LSLs) is unknown. Endoscopic mucosal resection (EMR) is a definitive therapy for colorectal LSLs. It is unclear whether it is an effective modality for ARJ-LSLs.

Design

EMR outcomes for ARJ-LSLs (distal margin of ≤20 mm from the dentate line) in comparison with rectal LSLs (distal margin of >20 mm from the dentate line) were evaluated within a multicentre observational cohort of LSLs of ≥20 mm. Technical success was defined as the removal of all polypoid tissue during index EMR. Safety was evaluated by the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury (DMI) and delayed perforation. Long-term efficacy was evaluated by the absence of recurrence (either endoscopic or histologic) at surveillance colonoscopy (SC).

Results

Between July 2008 and August 2019, 100 ARJ-LSLs and 313 rectal LSLs underwent EMR. ARJ-LSL median size was 40 mm (IQR 35–60 mm). Median follow-up at SC4 was 54 months (IQR 33–83 months). Technical success was 98%. Cancer was present in three (3%). Recurrence occurred in 15.4%, 6.8%, 3.7% and 0% at SC1–SC4, respectively. Among 30 ARJ-LSLs that received margin thermal ablation, no recurrence was identified at SC1 (0.0% vs 25.0%, p=0.002). Technical success, recurrence and adverse events were not different between groups, except for DMI (ARJ-LSLs 0% vs rectal LSLs 4.5%, p=0.027).

Conclusion

EMR is an effective technique for ARJ-LSLs and should be considered a first-line resection modality for the majority of these lesions.
Intraoperative frozen section consultation by remote whole-slide imaging analysis –validation and comparison to robotic remote microscopy
Authors: Menter Thomas , Nicolet Stefan , Baumhoer Daniel , Tolnay Markus , Tzankov Alexandar
Published: November 2019

Digital pathology including whole slide image (WSI) acquisition is a promising tool for histopathologic teleconsultation. To test and validate the use of WSI in comparison with robotic microscopy for intraoperative frozen section consultation of peripheral hospitals serviced by our department, we compared the VENTANA DP 200 slide scanner with an established remote-controlled digital microscope. Thirty cases were retrospectively analysed. In comparison with a median specimen handling time of 19 min using remote-controlled microscopy, the WSI handling was significantly shorter (11 min, p=0.0089) and offered better image quality, for example, allowing to detect a positive resection margin by a malignant melanoma that had been missed using the former system. Prospectively assessed on 12 cases, the median handling time was 6 min. Here, we demonstrate the applicability and the advantages of WSI for intraoperative frozen section teleconsultation. WSI-based telepathology prooves to be an efficient and reliable tool providing superior turn-around time and image resolution.
Autonomy, voluntariness and assisted dying
Authors: Colburn Ben
Published: November 2019

Ethical arguments about assisted dying often focus on whether or not respect for an individual’s autonomy gives a reason to offer them an assisted death if they want it. In this paper, I present an argument for legalising assisted dying which appeals to the autonomy of people who don’t want to die. Adding that option can transform the nature of someone’s choice set, enabling them to pursue other options voluntarily where that would otherwise be harder or impossible. This does not contradict the more familiar arguments for legalising assisted dying based on the autonomy of those who seek to die. But it does suggest that a wider constituency of support for that legislative change might be created by emphasising that one need not be in that position to be benefited by the change.
Aortic valve repair techniques: an early UK experience
Authors: Greco Renata , Muretti Mirko , Jin Xu Yu , Petrou Mario
Published: November 2019

Objectives

Retrospective review of early results with aortic valve repair (AVr) techniques.

Methods

61 consecutive patients underwent AVr surgery at our institutions between 2008 and 2018. 14 patients had a bicuspid aortic valve and 16 had a connective tissue disorder. In 48 patients, aortic regurgitation (AR) was secondary to an aortic root and/or ascending aneurysms, while in 13 it was due to primary cusp pathologies. 13 patients underwent isolated cusp repair, 19 sinotubular junction remodelling, 25 valve-sparing root replacement (VSRR) and 4 hemiroot replacement. Cusp repair techniques included: 18 free margin plication, 18 commissural re-suspensions, 3 raphe resections and 1 free-edge reinforcement. Subcommissural annuloplasty was performed in 25 patients (42%) with a dilated annulus (>28 mm).

Results

50 patients (82%) left the operating theatre with no AR, 8 with mild central and 3 with mild eccentric AR. In-hospital survival was 100%. Clinical follow-up was complete at 5.08±2.29 years and all patients were alive. Transthoracic echocardiographic follow-up was complete at 2.35±1.92 years and showed the presence of a moderate AR in 10 patients (18%) and severe AR in 2 patients (4%). One of these required re-do aortic valve replacement 6 years after VSRR. Freedom from re-operation at 8 years was 88.15%±1.51%.

Conclusion

Good early results are achievable following AVr with acceptable medium-term outcomes. AVr surgery continues to evolve, and concentrating the experience in specialist centres in the UK is recommended.
Early follow-up after open heart valve surgery reduces healthcare costs: a propensity matched study
Authors: Borregaard Britt , Møller Jacob Eifer , Dahl Jordi Sanchez , Riber Lars Peter Schødt , Berg Selina Kikkenborg , Ekholm Ola , Weiss Marc Gjern , Lykking Emilie Karense , Sibilitz Kirstine Lærum , Sørensen Jan
Published: November 2019

Objectives

The objective was to assess differences in healthcare costs within 180 days after discharge from open heart valve surgery in an intervention group receiving early, individualised and intensified follow-up compared with a historical control group.

Methods

A cost-minimisation analysis comparing costs from a consecutive prospective cohort compared with a propensity matched cohort. Costs related to the intervention, hospital (outpatient visits and readmissions) and general practitioners (all contacts) were included. Data were obtained from electronic patient records and registry data. A logistic propensity model was used to identify the historical control group. Main results are presented as mean differences and 95% CIs based on bootstrapping.

Results

After matching, the analysis included 300 patients from the intervention group and 580 controls. The mean intervention cost was €171 (SD 79) per patient. After 180 days, the mean healthcare costs were €1284 (SD 2567) for the intervention group and €2077 (SD 4773) for the controls. The cost of the intervention group was €793 (p<0.001) less per patient. The cost differences were explained mainly by fewer readmissions, fewer overall emergency visits and fewer contacts to the general practitioner during out-of-hours in the intervention group.

Conclusions

The intervention consisting of early, individualised and intensified follow-up after open heart valve surgery significantly reduced the healthcare costs within 180 days after discharge.
Trichomonas vaginalis
, endometritis and sequelae among women with clinically suspected pelvic inflammatory disease
Authors: Wiringa Ann E , Ness Roberta B , Darville Toni , Beigi Richard H , Haggerty Catherine L
Published: November 2019

Objective

To ascertain the prevalence of
Trichomonas vaginalis
and investigate associations between trichomoniasis, endometritis and sequelae among women with pelvic inflammatory disease (PID).

Methods

We assessed the prevalence of trichomoniasis identified via wet mount and its association with histologically confirmed endometritis, infertility and recurrent PID among 647 women in the PID Evaluation and Clinical Health (PEACH) study. Participants were treated for clinically suspected PID and followed for a mean of 84 months for incident sequelae. Analyses were adjusted for age, race,
Chlamydia trachomatis
,
Neisseria gonorrhoeae
,
Mycoplasma genitalium
and bacterial vaginosis. Additional adjustments were incorporated for history of infertility (models of pregnancy and infertility), history of PID (recurrent PID), and self-reported partner treatment and intercourse between baseline and 30-day follow-up (persistent endometritis).

Results

T. vaginalis
was present in the vagina of 12.8% of women. The odds of having endometritis at baseline were twice as high among women with trichomoniasis as compared with those without (adjusted OR (AOR): 1.9, 95% CI 1.0 to 3.3). Persistent endometritis was highly prevalent at 30 days (52.1%) and more common among women with baseline trichomoniasis (AOR: 2.6, 95% CI 0.7 to 10.1), although non-significantly. Infertility and recurrent PID were more common among women with trichomoniasis, while rates of pregnancy and live birth were lower.

Conclusions

T. vaginalis
was frequently isolated from the vagina of women with PID in the PEACH cohort. Wet mount microscopy for the identification of motile trichomonads was standard practice at the time of the PEACH study, but likely resulted in an underestimation of true
T. vaginalis
prevalence. Our findings of modest, although non-significant, prospective associations between trichomoniasis and sequelae are novel and underscore the need for additional investigation into whether
T. vaginalis
may play an aetiological role in adverse reproductive and gynaecological outcomes.
Intraoperative REBOA: an analysis of the American Association for the Surgery of Trauma AORTA registry
Authors: Vella Michael A , Dumas Ryan Peter , DuBose Joseph , Morrison Jonathan , Scalea Thomas , Moore Laura , Podbielski Jeanette , Inaba Kenji , Piccinini Alice , Kauvar David S , Baggenstoss Valorie L , Spalding Chance , Fox Charles , Moore Ernest E , Cannon Jeremy W
Published: November 2019

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less-invasive technique for aortic occlusion (AO). Commonly performed in the emergency department (ED), the role of intraoperative placement is less defined. We hypothesized that operating room (OR) placement is associated with increased in-hospital mortality.

Methods

The American Association for the Surgery of Trauma AORTA registry was used to identify patients undergoing REBOA. Injury characteristics and outcomes data were compared between OR and ED groups. The primary outcome was in-hospital mortality; secondary outcomes included total AO time, transfusion requirements, and acute kidney injury.

Results

Location and timing of catheter insertion were available for 305 of 321 (95%) subjects. 58 patients underwent REBOA in the OR (19%). There were no differences with respect to sex, admission lactate, and Injury Severity Score. The OR group was younger (33 years vs. 41 years, p=0.01) and with more penetrating injuries (36% vs. 15%, p<0.001). There were significant differences with respect to admission physiology. Time from admission to AO was longer in the OR group (75 minutes vs. 23 minutes, p<0.001) as was time to definitive hemostasis (116 minutes vs. 79 minutes, p=0.01). Unadjusted mortality was lower in the OR group (36.2% vs. 68.8%, p<0.001). There were no differences in secondary outcomes. After controlling for covariates, there was no association between insertion location and in-hospital mortality (OR 1.8, 95% CI 0.30 to 11.50).

Discussion

OR REBOA placement is common and generally employed in patients with more stable admission physiology. OR placement was not associated with increased in-hospital mortality despite longer times to AO and definite hemostasis when compared with catheters placed in the ED.

Level of evidence

IV; therapeutic/care management.
Dynamically assisted Schwinger effect at strong coupling with its holographic extension
Authors: Lan Chen , Wang Yi-Fan , Geng Huifang , Andreev Alexander
Published: November 2019

At strong-coupling and weak-field limit, the scalar Schwinger effect is studied by the field-theoretical method of worldline instantons for dynamic fields of single-pulse and sinusoidal types. By examining the Wilson loop along the closed instanton path, corrections to the results obtained from weak-coupling approximations are discovered. They show that this part of contribution for production rate becomes dominant as Keldysh parameter increases, it makes the consideration at strong coupling turn out to be indispensable for dynamic fields. Moreover a breaking of weak-field condition similar to constant field also happens around the critical field, defined as a point of vacuum cascade. In order to make certain whether the vacuum cascade occurs beyond the weak-field condition, following Semenoff and Zarembo’s proposal, the Schwinger effects of dynamic fields are studied with an $${\mathcal {N}}=4$$N=4 supersymmetric Yang–Mills theory in the Coulomb phase. With the help of the gauge/gravity duality, the vacuum decay rate is evaluated by the string action with instanton worldline as boundary, which is located on a probe D3–brane. The corresponding classical worldsheets are estimated by perturbing the integrable case of a constant field.
Nanoshell Si/Cu composites as anode materials for lithium ion battery
Authors: Zhang Manshu , Shen Lian , Liu Yangai
Published: November 2019

The chemical plating methods were used to prepare nanoshell Si/Cu composites. The methods delivered a high initial discharge and charge capacity of 1312.1 and 1008.8 mAh/g, respectively. The electrochemical properties of the composites retained about 662.6 mAh/g after 100 cycles. The Cu coating improved the electrical conductivity but hindered the direct contact of the Si particles and the electrolyte, which suppressed the SEI growth.
Model-based analysis of geometrical effects in microfluidic fuel cell with flow-through porous electrodes
Authors: Xu Qiang , She Yiyi , Li Li
Published: November 2019

Porous electrodes in microfluidic fuel cell (MFC) operate with nonuniform reaction rate. It is intriguing to improve the utilization degree of the porous electrodes. In this work, a three-dimensional computational model is developed for MFC with flow-through porous electrodes. Characteristics of the reaction rate distributions under different electrode geometries are examined. The results show that reaction rate varies noticeably along the electrode width direction, but minimally along the electrode length direction. High reaction rate region locates in the vicinity of the interface between the porous electrode and the middle channel. A relatively high aspect ratio, defined as the ratio of the electrode length to width, is beneficial to improve the utilization degree of the porous electrodes. Yet, concentration losses increase due to the decreased fluid velocity. Considering the cell performance, optimal electrode aspect ratios are derived for the anode and cathode, respectively.
Analytical methods via bright–dark solitons and solitary wave solutions of the higher-order nonlinear Schrödinger equation with fourth-order dispersion
Authors: Seadawy Aly R. , Iqbal Mujahid , Lu Dianchen
Published: November 2019

In this research work, we investigated the higher-order nonlinear Schrödinger equation (NLSE) with fourth-order dispersion, self-steepening, nonlinearity, nonlinear dispersive terms and cubic-quintic terms which is described as the propagation of ultra-short pulses in fiber optics. We apply the modification form of extended auxiliary equation mapping method to find the new exact and solitary wave solutions of higher-order NLSE. As a result, new solutions are obtained in the form of solitons, kink–anti-kink type solitons, bright–dark solitons, traveling wave, trigonometric functions, elliptic functions and periodic solitary wave solutions. These new different types of solutions show the power and fruitfulness of this new method and also show two- and three-dimensional graphically with the help of computer software Mathematica. These new solutions have many applications in the field of physics and other branches of physical sciences. We can also solve other higher-order nonlinear partial differential equations (NPDEs) involved in mathematical physics and other various branches of physical sciences with this new technique.
Transverse magnetic flow over a Reiner–Philippoff nanofluid by considering solar radiation
Authors: Reddy M. Gnaneswara , Rani Sudha , Kumar K. Ganesh , Seikh Asiful H. , Rahimi-Gorji Mohammad , Sherif El-Sayed Mohmed
Published: November 2019

This paper reports the flow and heat transfer augmentation on Reiner–Philippoff nanofluid over stretching sheet. The effect of transverse magnetic field and thermal radiation are explored for temperature distributions. Transformations are used to reduce system of partial differential equations into ordinary ones and are solved numerically by using RKF-45 Method. Expressions for velocity and temperature profile are derived and plotted under the assumption of flow parameter. Influence of various parameters on surface drag force and heat transfer rates have been discussed with the help of tables and plots. It is noticed that the impact of pseudo plastic fluid, Newtonian fluid and dilatant fluid are highly contrasted in higher Ha. Furthermore, production of heat transfer is more in nonlinear radiation when compared to linear radiation.
The Wriggle polynomial for virtual tangles
Authors: Petit Nicolas
Published: November 2019

We generalize the Wriggle polynomial, first introduced by L. Folwaczny and L. Kauffman, to the case of virtual tangles. This generalization naturally arises when considering the self-crossings of the tangle. We prove that the generalizations (and, by corollary, the original polynomial) are Vassiliev invariants of order one for virtual knots, and study some simple properties related to the connected sum of tangles.
MARKET PRICE OF TRADING LIQUIDITY RISK AND MARKET DEPTH
Authors: KIJIMA MASAAKI , TING CHRISTOPHER
Published: November 2019

Price impact of a trade is an important element in pre-trade and post-trade analyses. We introduce a framework to analyze the market price of liquidity risk, which allows us to derive an inhomogeneous Bernoulli ordinary differential equation. We obtain two closed form solutions, one of which reproduces the linear function of the order flow in Kyle (1985) for informed traders. However, when traders are not as asymmetrically informed, an S-shape function of the order flow is obtained. We perform an empirical intra-day analysis on Nikkei futures to quantify the price impact of order flow and compare our results with industry’s heuristic price impact functions. Our model of order flow yields a rich framework to not only estimate the liquidity risk parameters, but also to provide a plausible cause of why volatility and correlation are stochastic in nature. Finally, we find that the market depth encapsulates the market price of liquidity risk.
GLOBAL AND REGIONAL RISKS IN CURRENCY RETURNS
Authors: RENDON JAIRO A.
Published: November 2019

This paper presents an asset-pricing model for an integrated financial economy in a multi-currency framework in which three risk dimensions drive asset prices: global risk, regional risk and country-specific risk. Under this framework, all risks are common since, by trading assets across countries, agents can load on foreign risk. However, the model’s solution imposes restrictions on the loading coefficients. As a result, only the dispersion in global and regional coefficients is needed to explain currency returns. The model is tested with a linear-factor model at the currency-pair level using a sample of 42 countries located in five different regions. It is shown that, as the model predicted, regional and global factors help explain the dispersion in currency returns.
Seismic Response of Concrete-Canvas Reinforced Slopes: Influence of Tilt Degrees for Reinforcement
Authors: Zhou Lin , Ding Guangya , Tan Jie , Zhao Xiaoxia , Wang Jun
Published: November 2019

A series of shaking table tests were conducted on reinforced slopes to study the slope dynamic characteristics. The influence of concrete-canvas tilt degrees on the seismic response was studied. By considering the effects of different concrete-canvas tilt degrees, the seismic responses of the reinforced slopes were analyzed, along with the accelerations, crest settlements, and horizontal displacements. The failure patterns of different model slopes were compared using white coral sand marks placed at designated elevations to monitor the internal slide of the reinforced slopes. Several round markers were placed on the slope surface to compare the deformation before and after shaking with different amplitudes. The results indicated that with the increase in concrete-canvas tilt degrees, a better reinforcing effect was obtained, and 30° reinforcement reached a threshold level, the slide-out point shifts from the crest of the slope to the middle of the reinforced model. The bottom 2/7th zone of the slope was relatively stable during the earthquake and the reinforcement was ineffective at the bottom of the slope. When both considered the influence of reinforcing effect and construction difficulty, 20° is the suitable tilt degree in concrete-canvas reinforced slopes. The characteristics of increasing strength of the concrete canvas make it suitable for the application in slope protection.
Universality for conditional measures of the Bessel point process
Authors: Molag Leslie D. , Stevens Marco
Published: November 2019

The Bessel point process is a rigid point process on the positive real line and its conditional measure on a bounded interval [Formula: see text] is almost surely an orthogonal polynomial ensemble. In this paper, we show that if [Formula: see text] tends to infinity, one almost surely recovers the Bessel point process. In fact, we show this convergence for a deterministic class of probability measures, to which the conditional measure of the Bessel point process almost surely belongs.
Co-Evolution of Technology and Institutions in Emerging Industries: Case from Electric Vehicles in China
Authors: Sui Jigang , Liu Ying
Published: November 2019

Technology and institutions are important driving forces for industrial development, but the relationship between them has not yet reached a consensus due to different economic theories. On the basis of the evolutionary theory, this paper aims to study the roles co-evolution of technology and institutions played in the development of emerging industry. Taking electric vehicles in China as a case study and the five-year plans for the nodes of industrial development, this paper analyzes the co-evolutionary process of technology and institutions at different stages of industrial development, and concludes that it was institutions that promoted technology innovation during the industrial incubation and infancy periods, while during the growth period, it was technology that drove institutions’ innovation. In order to promote the development of electric vehicle industry, it is necessary to further strengthen institutional innovation for technological and industrial development.
Attention Models in Graphs
Authors: Lee John Boaz , Rossi Ryan A. , Kim Sungchul , Ahmed Nesreen K. , Koh Eunyee
Published: November 2019

Graph-structured data arise naturally in many different application domains. By representing data as graphs, we can capture entities (i.e., nodes) as well as their relationships (i.e., edges) with each other. Many useful insights can be derived from graph-structured data as demonstrated by an ever-growing body of work focused on graph mining. However, in the real-world, graphs can be both large—with many complex patterns—and noisy, which can pose a problem for effective graph mining. An effective way to deal with this issue is to incorporate “attention” into graph mining solutions. An attention mechanism allows a method to focus on task-relevant parts of the graph, helping it to make better decisions. In this work, we conduct a comprehensive and focused survey of the literature on the emerging field of graph attention models. We introduce three intuitive taxonomies to group existing work. These are based on problem setting (type of input and output), the type of attention mechanism used, and the task (e.g., graph classification, link prediction). We motivate our taxonomies through detailed examples and use each to survey competing approaches from a unique standpoint. Finally, we highlight several challenges in the area and discuss promising directions for future work.
Understanding the Role of Racism in Contemporary US Public Opinion
Authors: Cramer Katherine
Published: November 2019

In the contemporary context, it is inescapable that racism is a factor in US public opinion. When scholars take stock of the way we typically measure and conceptualize racism, we find reason to reconceptualize the racial resentment scale as a measure of perceptions of the reasons for political inequality. We also see reason to move beyond thinking of racism as an attitude, toward conceptualizing it as a perspective. In addition, we see reason to pay closer attention to the role of elites in creating and perpetuating a role for racism in the way people think about public affairs. The study of racism is evolving in parallel with the broader public discussion: toward a recognition of the complex and fundamental ways it is woven into US culture and political life.
Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus
Authors: Li Qing , Liu Dexiang , Pan Fang , Ho Cyrus S. H. , Ho Roger C. M.
Published: November 2019

The ethanol-induced toll-like receptor 4 (TLR4) signal activation of microglia and neuroinflammation are observed in both adolescent and adult rat brains, but the regulatory mechanisms of some TLR4 signaling-related factors in this process are still unclear. SUMO-specific protease 6 (SENP6) inhibits neuroinflammation by dampening nuclear factor kappa-B (NF-κB) activation via the de-SUMOylation of NF kappa-B essential modulator (NEMO). This study investigates the effects of long-term ethanol consumption on neuroinflammation in the hippocampus of adolescent rats and the regulatory roles of TLR4 and SENP6. Twenty-one days of ethanol exposure in adolescent rats were used to develop an animal model. The number of microglia, microglial activation, and the expression of TLR4 in the hippocampus of adolescent rats were examined by immunoreactivity. The levels of TLR4, activation of NF-κB including IkB-α and p-NF-κB-p65, and SENP6 were measured by western blotting. Proinflammatory cytokines including TNF-α, IL-1β, and IL-6 were measured by enzyme-linked immunosorbent assay. The NF-κB activation and proinflammatory cytokines released in overexpressed SENP6 and siRNA targeting SENP6 microglial cells after treatment with ethanol were estimated in vitro. This study found that alcohol exposure increased the number of activated microglia and the levels of p-NF-κB-p65 and proinflammatory cytokines, while it decreased the SENP6 level in wild-type rats, but not in TLR4 knockout rats. The ethanol-induced increases of p-NF-κB-p65, TNF-α, and IL-1β were dampened by overxpression of SENP6 and enhanced in SENP6-siRNA microglia. Our data suggest that ethanol exposure during adolescence induces the microglia-mediated neuroinflammation via TLR4 activation, and SENP6 plays an essential role in dampening NF-κB activation and neuroinflammation.
Ethyl Vanillin Protects against Kidney Injury in Diabetic Nephropathy by Inhibiting Oxidative Stress and Apoptosis
Authors: Tong Yuna , Liu Shan , Gong Rong , Zhong Lei , Duan Xingmei , Zhu Yuxuan
Published: November 2019

Diabetes-induced oxidative stress and apoptosis is regarded as a critical role in the pathogenesis of diabetic nephropathy (DN). Treating diabetes-induced kidney damage and renal dysfunction has been thought a promising therapeutic option to attenuate the development and progression of DN. In this study, we investigated the renoprotective effect of ethyl vanillin (EVA), an active analogue of vanillin isolated from vanilla beans, on streptozotocin- (STZ-) induced rat renal injury model and high glucose-induced NRK-52E cell model. The EVA treatment could strongly improve the deterioration of renal function and kidney cell apoptosis in vivo and in vitro. Moreover, treating with EVA significantly decreased the level of MDA and reactive oxygen species (ROS) and stabilized antioxidant enzyme system in response to oxidative stress by enhancing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro. Furthermore, EVA also markedly suppressed cleaved caspase-3, Bax, and nuclear transcription factor erythroid 2-related factor (Nrf2) expression in STZ-induced rats. Therefore, these results of our investigation provided that EVA might protect against kidney injury in DN by inhibiting oxidative stress and cell apoptosis.
Iron Overload Damages the Endothelial Mitochondria via the ROS/ADMA/DDAHII/eNOS/NO Pathway
Authors: He Huan , Qiao Yang , Zhou Qing , Wang Zhiqing , Chen Xuepiao , Liu Dan , Yin Dong , He Ming
Published: November 2019

It has been recognized that iron overload may harm the body’s health. Vascular endothelial cells (VECs) are one of the main targets of iron overload injury, and the mechanism involved was thought to be related to the excessive generation of reactive oxygen species (ROS). However, the subcellular and temporal characteristics of ROS generation, potential downstream mechanisms, and target organelles in VECs injured by iron overload have not been expounded yet. In this study, we elucidated the abovementioned issues through both in vivo and in vitro experiments. Mice were fed pellet diets that were supplemented with iron for 4 consecutive months. Results showed that the thoracic aortic strips’ endothelium-dependent dilation was significantly impaired and associated with inflammatory changes, noticeable under brown TUNEL-positive staining in microscopy analysis. In addition, the serum content of asymmetric dimethylarginine (ADMA) increased, whereas nitric oxide (NO) levels decreased. Furthermore, the dimethylarginine dimethylaminohydrolase II (DDAHII) expression and activity, as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) in aortic tissue, were inhibited. Human umbilical vein endothelial cells were treated with 50 μM iron dextran for 48 hours, after which the cell viability, NO content, DDAHII expression and activity, and phosphorylation of eNOS decreased and lactate dehydrogenase and caspase-3 activity, ADMA content, and apoptotic cells significantly increased. After the addition of L-arginine (L-Arg) or pAD/DDAHII, the abovementioned changes were reversed. By dynamically detecting the changes of ROS generation in the cytoplasm and mitochondria and interfering with different aspects of signaling pathways, we have confirmed for the first time that excessive ROS originates from the cytoplasm and activates the ROS-induced ROS release (RIRR) mechanism, leading to mitochondrial dysfunction. Together, our data suggested that excessive free iron ions produced excess ROS in the cytoplasm. Thus, excess ROS create one vicious circle by activating the ADMA/eNOS/DDAHII/NO pathway and another vicious circle by activation of the RIRR mechanism, which, when combined, induce a ROS burst, resulting in mitochondrial dysfunction and damaged VECs.
Mutation Profiling of Premalignant Colorectal Neoplasia
Authors: Karczmarski Jakub , Goryca Krzysztof , Pachlewski Jacek , Dabrowska Michalina , Pysniak Kazimiera , Paziewska Agnieszka , Kulecka Maria , Lenarcik Malgorzata , Mroz Andrzej , Mikula Michal , Ostrowski Jerzy
Published: November 2019

Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis.
Exploring the Biomarkers of Sepsis-Associated Encephalopathy (SAE): Metabolomics Evidence from Gas Chromatography-Mass Spectrometry
Authors: Zhu Jing , Zhang Mu , Han Tingli , Wu Hua , Xiao Zhibo , Lin Shihui , Wang Chuanjiang , Xu Fang
Published: November 2019

Background. Sepsis-associated encephalopathy (SAE) is a transient and reversible brain dysfunction, that occurs when the source of sepsis is located outside of the central nervous system; SAE affects nearly 30% of septic patients at admission and is a risk factor for mortality. In our study, we sought to determine whether metabolite changes in plasma could be a potential biomarker for the early diagnosis and/or the prediction of the prognosis of sepsis. Method. A total of 31 SAE patients and 28 healthy controls matched by age, gender, and body mass index (BMI) participated in our study. SAE patients were divided into four groups according to the Glasgow Coma Score (GCS). Plasma samples were collected and used to detect metabolism changes by gas chromatography-mass spectrometry (GC-MS). Analysis of variance was used to determine which metabolites significantly differed between the control and SAE groups. Results. We identified a total of 63 metabolites that showed significant differences among the SAE and control groups. In particular, the 4 common metabolites in the four groups were 4-hydroxyphenylacetic acid; carbostyril, 3-ethyl-4,7-dimethoxy (35.8%); malic acid peak 1; and oxalic acid. The concentration of 4-hydroxyphenylacetic acid in sepsis patients decreased with a decrease of the GCS. Conclusions. According to recent research on SAE, metabolic disturbances in tissue and cells may be the main pathophysiology of this condition. In our study, we found a correlation between the concentration of 4-hydroxyphenylacetic acid and the severity of consciousness disorders. We suggest that 4-hydroxyphenylacetic acid may be a potential biomarker for SAE and useful in predicting patient prognosis.
Optimizing the Pairs‐Trading Strategy Using Deep Reinforcement Learning with Trading and Stop‐Loss Boundaries
Authors: Kim Taewook , Kim Ha Young
Published: November 2019

Many researchers have tried to optimize pairs trading as the numbers of opportunities for arbitrage profit have gradually decreased. Pairs trading is a market‐neutral strategy; it profits if the given condition is satisfied within a given trading window, and if not, there is a risk of loss. In this study, we propose an optimized pairs‐trading strategy using deep reinforcement learning—particularly with the deep Q‐network—utilizing various trading and stop‐loss boundaries. More specifically, if spreads hit trading thresholds and reverse to the mean, the agent receives a positive reward. However, if spreads hit stop‐loss thresholds or fail to reverse to the mean after hitting the trading thresholds, the agent receives a negative reward. The agent is trained to select the optimum level of discretized trading and stop‐loss boundaries given a spread to maximize the expected sum of discounted future profits. Pairs are selected from stocks on the S&P 500 Index using a cointegration test. We compared our proposed method with traditional pairs‐trading strategies which use constant trading and stop‐loss boundaries. We find that our proposed model is trained well and outperforms traditional pairs‐trading strategies.
Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
Authors: Agata Hideki , Sumita Yoshinori , Hidaka Tatsuro , Iwatake Mayumi , Kagami Hideaki , Asahina Izumi
Published: November 2019

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.
Insulator Segmentation for Power Line Inspection Based on Modified Conditional Generative Adversarial Network
Authors: Gao Zishu , Yang Guodong , Li En , Shen Tianyu , Wang Zhe , Tian Yunong , Wang Hao , Liang Zize
Published: November 2019

There are a large number of insulators on the transmission line, and insulator damage will have a major impact on power supply security. Image-based segmentation of the insulators in the power transmission lines is a premise and also a critical task for power line inspection. In this paper, a modified conditional generative adversarial network for insulator pixel-level segmentation is proposed. The generator is reconstructed by encoder-decoder layers with asymmetric convolution kernel which can simplify the network complexity and extract more kinds of feature information. The discriminator is composed of a fully convolutional network based on patchGAN and learns the loss to train the generator. It is verified in experiments that the proposed method has better performances on mIoU and computational efficiency than Pix2pix, SegNet, and other state-of-the-art networks.
Contrast-Enhanced MRI Texture Parameters as Potential Prognostic Factors for Primary Central Nervous System Lymphoma Patients Receiving High-Dose Methotrexate-Based Chemotherapy
Authors: Chen Chaoyue , Zhuo Hongyu , Wei Xiawei , Ma Xuelei
Published: November 2019

Introduction. The purpose of this study was to evaluate the prognostic value of texture features on contrast-enhanced magnetic resonance imaging (MRI) for patients with primary central nervous system lymphoma (PCNSL). Methods. In this retrospective study, fifty-two patients diagnosed with PCNSL were enrolled from October 2010 to March 2017. The texture feature of tumor tissue on the histogram-based matrix (histo-) and the grey-level co-occurrence matrix (GLCM) was retrieved by contrast-enhanced T1-weighted imaging before any antitumor treatment. Receiver operating characteristic curve analyses were performed to obtain their optimal cutoff values, based on which we dichotomized patients into subgroups. The Kaplan–Meier analyses were conducted to compare overall survival (OS) of subgroups, and multivariate Cox regression analyses were used to determine if they could be taken as independent prognostic factors. Results. Ten texture features were extracted from the MR image, including Energy, Entropy, Kurtosis, Skewness on the histogram-based matrix, and Correlation, Contrast, Dissimilarity, Energy, Entropy, and Homogeneity on the grey-level co-occurrence matrix. Three of them (GLCM-Contrast, GLCM-Dissimilarity, and GLCM-Homogeneity) are shown to be significant in relation to overall survival (OS). The multivariate Cox regression analyses suggest that GLCM-Homogeneity could be taken as independent predictors. Conclusions. The texture features of contrast-enhanced magnetic resonance imaging (MRI) could potentially serve as prognostic biomarkers for PCNSL patients.
Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis
Authors: Wojdasiewicz Piotr , Turczyn Pawel , Dobies-Krzesniak Barbara , Frasunska Justyna , Tarnacka Beata
Published: November 2019

Osteoporosis is a civilization disease which is still challenging for contemporary medicine in terms of treatment and prophylaxis. It results from excessive activation of the osteoclastic cell line and immune cells like macrophages and lymphocytes. Cell-to-cell inflammatory information transfer occurs via factors including cytokines which form a complex network of cell humoral correlation, called cytokine network. Recently conducted studies revealed the participation of CX3CL1 chemokine in the pathogenesis of osteoporosis. CX3CL1 and its receptor CX3CR1 present unique properties among over 50 described chemokines. Apart from its chemotactic activity, CX3CL1 is the only chemokine which may function as an adhesion molecule which facilitates easier penetration of immune system cells through the vascular endothelium to the area of inflammation. The present study, based on world literature review, sums and describes convincing evidences of a significant role of the CX3CL1/CX3CR1 axis in processes leading to bone mineral density (BMD) reduction. The CX3CL1/CX3CR1 axis plays a principal role in osteoclast maturation and binding them with immune cells to the surface of the bone tissue. It promotes the development of inflammation and production of many inflammatory cytokines near the bone surface (i.e., TNF-α, IL-1β, and IL-6). High concentrations of CX3CL1 in serum are directly proportional to increased concentrations of bone turnover and inflammatory factors in human blood serum (TRACP-5b, NTx, IL-1β, and IL-6). Regarding the fact that acting against the CX3CL1/CX3CR1 axis is a potential target of immune treatment in osteoporosis, the number of available papers tackling the topic is certainly insufficient. Therefore, it seems justified to continue research which would precisely determine its role in the metabolism of the bone tissue as one of the most promising targets in osteoporosis therapy.
Metastatic Multiple Myeloma to the Skin
Authors: Holliday Alex C. , Khan Mohammed I. , Mazloom Sean E. , Chavan Rahul N. , Grider Douglas J.
Published: November 2019

Cutaneous involvement of multiple myeloma (MM) is uncommon, typically occurs in late stage disease, and is a poor prognostic indicator with an approximate eight month median survival. We present a 51-year-old man with relapsed lambda light chain MM who developed abrupt asymptomatic skin metastases. Biopsy revealed a dermis replete of atypical plasma cells, positive for CD138 and CD45. In situ hybridization confirmed lambda light chain restriction. Despite rescue antimyeloma therapy with the anti-CD38 drug daratumumab, he rapidly declined clinically and succumbed to the disease four weeks after presentation. A standard treatment approach for cutaneous MM does not currently exist; however, various techniques to detect cytogenetic abnormalities are emerging and will provide additional prognostic value and direct individualized therapy.
Lead Poisoning and Intelligence: A Search for Cause and Effect in the Scottish Mental Surveys
Authors: Krebs Conrad
Published: November 2019

In 1932 and again in 1947, the Scottish Council for Research in Education conducted the Scottish Mental Surveys. Testing two cohorts, one in 1932 and another in 1947, researchers set out to measure—using the same validated test each time—the intelligence of every Scottish child 11 years of age. The stated impetus for the Surveys was a fear that average Scottish intelligence was declining. But when investigators compared the results of the 1947 Survey with those from 1932 their predictions were completely upended. Instead of average intelligence declining, it had risen, substantially. The author argues that based on a study of the relevant ecosystems in place in Scotland at the time the increase in intelligence resulted from a decline in lead body burden. There is no evidence that the children were tested for lead. The decline is thought to have closely followed a fall in occupational lead use, a heightened awareness of the dangers of lead-solvency, improvements in lead plumbing in working-class homes, and a national campaign to improve the nutrition of women and children. Evidence shows that milk consumption in Scotland increased sharply, especially among children, beginning in the mid-1930s, just prior to and following the birth of the second cohort. This provided a source of calcium in a diet that had shown signs of deficiency. Evidence also suggests that lead contamination, from lead water pipes and industrial sources, was widely prevalent in Scotland in the early part of the twentieth century.