bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymph node number, surface area and lymph node ratio are important prognostic indicators in neoadjuvant chemoradiotherapy treated rectal cancer
Authors: Pitto Francesca , Zoppoli Gabriele , Scabini Stefano , Romairone Emanuele , Fiocca Roberto , Ballestrero Alberto , Sparavigna Marco , Malaspina Lara , Valle Luca , Grillo Federica , Mastracci Luca
Published: September 2019

Aims

Neoadjuvant chemoradiotherapy (neoCRT) is recommended for locally advanced rectal cancer (RC), however, this often makes lymph node (LN) search trying. The aim of this study was to evaluate, in a large retrospective, monocentric, series of post-neoCRT-RC patients, the importance of LN number, ratio and surface area in predicting metastases, overall survival (OS) and disease free survival (DFS).

Methods

104 patients with RC underwent total mesorectal excision, after standard neoCRT. All resected specimens were examined according to a standardised sampling/histopathological protocol. The following data regarding LNs were collected: total numbers; number with metastases; LNratio (metastatic/total); maximum diameter; surface area.

Results

A statistically significant association was found between LN number and DFS (p=0.0473). Finding ≤9 or >20 LNs correlated with worse prognosis compared with 10–20 (p value=0.049). LNratio (>0.2) was strongly associated with shorter DFS (HR=13.36; p value <0.0001) and OS (HR=26.06; p value <0.0001). Poor outcome, for DFS (HR=2.17, p value =0.0416) and OS (HR=1.18, p value =0.0025), was associated with increasing LN surface area. LNratio was independently associated with DFS at multivariate analysis (p value <0.0001).

Conclusions

LN number, LNratio and LN surface area are important prognostic factors in neoCRT-RC and in particular finding ≤9 or >20 LNs is prognostically adverse.
Stress cardiomyopathy in stranded cetaceans: a histological, histochemical and immunohistochemical study
Authors: Câmara Nakita , Sierra Eva , Fernández‐Maldonado Carolina , Espinosa de los Monteros Antonio , Arbelo Manuel , Fernández Antonio , Herráez Pedro
Published: September 2019

Background

Free‐living cetaceans are exposed to a wide variety of stressful situations, including live stranding and interaction with human beings (capture myopathy), vessel strikes, and fishing activities (bycatch), which affect their wellbeing and potentially lead to stress cardiomyopathy (SCMP).

Methods

Here, the authors aimed to characterise SCMP of stranded cetaceans as an injury resulting from extreme stress responses, based on pathological analyses (histological, histochemical and immunohistochemical). Specifically, the authors examined heart samples from 67 cetaceans found ashore (48 live strandings, seven dead from ship collision and 12 dead from bycatch) on the coast of Spain, more specifically in the Canary Islands from 2000 to 2016 and Andalusia from 2011 to 2014.

Results

The microscopic findings were characterised by vascular changes, acute or subacute cardiac degenerative necrotic lesions, interstitial myoglobin globules, and infiltration of inflammatory cells. Immunohistochemically, cardiac troponin I, cardiac troponin C and myoglobin were depleted, along with fibrinogen being expressed in the degenerated/necrotic cardiomyocytes. A perivascular pattern was also identified and described in the damaged cardiomyocytes.

Conclusions

This study advances current knowledge about the pathologies of cetaceans and their implications on conserving this group of animals by reducing mortality and enhancing their treatment and subsequent rehabilitation to the marine environment.
Traditional sets versus rest-redistribution: a laboratory-controlled study of a specific cluster set configuration at fast and slow velocities
Authors: Tufano James J. , Omcirk Dan , Malecek Jan , Pisz Anna , Halaj Matej , Scott Brendan R.
Published: September 2019

This study investigated redistributing long inter-set rest intervals into shorter but more frequent intervals at 2 different concentric velocities. Resistance-trained men performed 4 randomised isokinetic unilateral knee extension protocols, 2 at 60°·s−1 and 2 at 360°·s−1. At each speed, subjects performed 40 repetitions with 285 s of rest using traditional sets (TS; 4 sets of 10 with 95 s of inter-set rest) and rest-redistribution (RR; 20 sets of 2 with 15 s inter-set rest). Before and at 2, 5, and 10 min after exercise, tensiomyography (TMG) and oxygenation (near-infrared spectroscopy; NIRS) were measured. NIRS was also measured during exercise, and rating of perceived exertion (RPE) was recorded after every 10 repetitions. At both speeds, RR displayed greater peak torque, total work, and power output during latter repetitions, but there were no differences between TS or RR when averaging all 40 repetitions. The RPE was less during RR at both speeds (p < 0.05). RR increased select muscle oxygen saturation and blood flow at both speeds. There were no effects of protocol on TMG, but effect sizes favoured a quicker recovery after RR. RR was likely beneficial in maintaining performance compared with the latter parts of TS sets and limiting perceived and peripheral fatigue.

Novelty Although effective at slow velocities, rest-redistribution was likely more effective during high-velocity movements in this study. Rest-redistribution maintained the ability to produce force throughout an entire range of motion. Rest-redistribution reduced RPE during both high-velocity and high-force movements.
Runout simulation of seismic landslides using discontinuous deformation analysis (DDA) with state-dependent shear strength model
Authors: Nian Ting-kai , Zhang Yan-jun , Wu Hao , Chen Guang-qi , Zheng Lu
Published: September 2019

The reliable numerical simulation of the landslide process contributes to the establishment of evidence-based disaster mitigation measures in seismically active zones. To achieve this goal, a simple and unified state-dependent shear strength model of discontinuities is presented to describe the shear strength degradation in a seismic landslide process. The proposed model establishes a relationship between the shear strength parameters and the global safety factor of the slope by assuming that the slope instability (or landslide initiation) is accompanied by an instantaneous shear strength degradation of discontinuities. To realize the model numerically, the algorithms for the computation of global safety factor and the modification of shear strength parameters were incorporated into the discontinuous deformation analysis (DDA). Subsequently, the kinematic accuracy of the improved DDA method was validated by comparisons with theoretical solutions for the dynamic sliding of a block on an inclined plane. Numerical simulations of the Daguangbao landslide triggered by the Wenchuan earthquake were performed using the improved DDA method. The results illustrate that the shear strength degradation of discontinuities affect the evolution process, travel distance, and post-failure shape of the seismic landslide significantly.
Guided TE-waves in a slab structure with lossless cubic nonlinear dielectric and magnetic material: parameter dependence and power flow with focus on metamaterials
Authors: Schürmann Hans Werner , Serov Valery
Published: September 2019

The parameter dependence and power flow of guided TE-waves in a lossless cubic nonlinear, dielectric, magnetic planar three-layer structure is studied as follows.
Using a travelling wave ansatz with stationary amplitude, Maxwell’s equations are transformed to a system of ordinary nonlinear differential equations.The solutions of the system are presented compactly (in terms of hyperbolic and elliptic functions).The nonnegative and bounded (“physical”) solutions are determined by using a phase diagram condition (PDC) that is applied to express the continuity (transmission) conditions at the interfaces leading to the dispersion relation (DR).Based on the PDC, the parameter dependence and stability of the solutions to the DR and corresponding power flow are studied numerically for permittivities and permeabilities that may be appropriate to describe metamaterial.
Solving a Class of Variational Inequality Problems with a New Inexact Strategy
Authors: Dong Xiaomei , Cai Xingju , Han Deren , Ge Zhili
Published: September 2019

We consider a class of variational inequality problems with linear constraints, where the mapping is unknown and the system is an oracle. The capacitated traffic congestion pricing problem of transportation is such an application, and many classical methods cannot deal with this class of problems. Note that the cost of the observation (observe the exact solution of the subproblem) is very expensive. It is important to get an inexact solution instead of an exact solution, especially when the iteration is far from the solution set. In this paper, we propose a modified inexact prediction–correction method. Under the mild condition that the underlying mapping is strongly monotone, we prove the global convergence. Some numerical examples are presented to illustrate the efficiency of the inexact strategy.
A Method of Interest Degree Mining Based on Behavior Data Analysis
Authors: Li Zhen , Xu Shuo , Wang Tianyu
Published: September 2019

Based on big data, this paper starts from the behavior data of users on social media, and studies and explores the core issues of user modeling under personalized services. Focusing on the goal of user interest modeling, this paper proposes corresponding improvement measures for the existing interest model, which has great difference in interest description among different users and it is difficult to find the user interest change in time. For the above problems, this paper takes user-generated content and user behavior information as the analysis object, and uses natural language processing, knowledge warehouse, data fusion and other methods and techniques to numerically analyze user interest mining based on text mining and multi-source data fusion. We propose a user interest label space mapping method to avoid data sparse problem caused by too many dimensions in interest analysis. At the same time, we propose a method to extract and blend the long-term and short-term interests, and realize the comprehensive evaluation of interests. In the analysis of the big data phase, the user preference social property application preference value law, it is expected to achieve user Internet social media application preference data mining from the perspective of big data.
Local and nonlocal phase-field models of tumor growth and invasion due to ECM degradation
Authors: Fritz Marvin , Lima Ernesto A. B. F. , Nikolić Vanja , Oden J. Tinsley , Wohlmuth Barbara
Published: September 2019

We present and analyze new multi-species phase-field mathematical models of tumor growth and ECM invasion. The local and nonlocal mathematical models describe the evolution of volume fractions of tumor cells, viable cells (proliferative and hypoxic cells), necrotic cells, and the evolution of matrix-degenerative enzyme (MDE) and extracellular matrix (ECM), together with chemotaxis, haptotaxis, apoptosis, nutrient distribution, and cell-to-matrix adhesion. We provide a rigorous proof of the existence of solutions of the coupled system with gradient-based and adhesion-based haptotaxis effects. In addition, we discuss finite element discretizations of the model, and we present the results of numerical experiments designed to show the relative importance and roles of various effects, including cell mobility, proliferation, necrosis, hypoxia, and nutrient concentration on the generation of MDEs and the degradation of the ECM.
Logical laws for short existential monadic second-order sentences about graphs
Authors: Zhukovskii M. E.
Published: September 2019

In 2001, Le Bars proved that there exists an existential monadic second-order (EMSO) sentence such that the probability that it is true on [Formula: see text] does not converge and conjectured that, for EMSO sentences with two first-order variables, the zero–one law holds. In this paper, we prove that the conjecture fails for [Formula: see text], and give new examples of sentences with fewer variables without convergence (even for [Formula: see text]).
A WKB formula for echoes
Authors: Sebastiani Lorenzo , Vanzo Luciano , Zerbini Sergio
Published: September 2019

We present a unified approach for the study of idealized gravitational compact objects like wormholes (WHs) and horizonless stars, here simulated by the presence of boundary conditions at a deeply inner wall. At the classical level, namely neglecting quantum effects, the presence of the wall leads to characteristic echoes following the usual ringdown phase, such that it can discriminate black holes from other horizonless, and probably exotic, compact objects. With regard to this issue, an analytical though approximated expression for the complex frequencies of the quasinormal echoes is found and discussed. At the quantum level, we show that static WHs do not radiate.
Comparing Sensory Organs to Define the Path for Hair Cell Regeneration
Authors: Denans Nicolas , Baek Sungmin , Piotrowski Tatjana
Published: September 2019

Deafness or hearing deficits are debilitating conditions. They are often caused by loss of sensory hair cells or defects in their function. In contrast to mammals, nonmammalian vertebrates robustly regenerate hair cells after injury. Studying the molecular and cellular basis of nonmammalian vertebrate hair cell regeneration provides valuable insights into developing cures for human deafness. In this review, we discuss the current literature on hair cell regeneration in the context of other models for sensory cell regeneration, such as the retina and the olfactory epithelium. This comparison reveals commonalities with, as well as differences between, the different regenerating systems, which begin to define a cellular and molecular blueprint of regeneration. In addition, we propose how new technical advances can address outstanding questions in the field.
Novel interaction of antioxidant-1 with TRAF4: role in inflammatory responses in endothelial cells
Authors: Das Archita , Sudhahar Varadarajan , Ushio-Fukai Masuko , Fukai Tohru
Published: September 2019

NADPH oxidase (NOX)-derived reactive oxygen species (ROS) and copper (Cu), an essential micronutrient, have been implicated in vascular inflammatory diseases. We reported that in proinflammatory cytokine TNF-α-stimulated endothelial cells (ECs), cytosolic Cu chaperone antioxidant-1 (Atox1) functions as a Cu-dependent transcription factor for the NOX organizer p47phox, thereby increasing ROS-dependent inflammatory gene expression. However, the role and mechanism of Atox1 nuclear translocation in inflamed ECs remain unclear. Using enface staining and nuclear fractionation, here we show that Atox1 was localized in the nucleus in inflamed aortas from ApoE−/− mice with angiotensin II infusion on a high-fat diet, while it was found in cytosol in those from control mice. In cultured human ECs, TNF-α stimulation promoted Atox1 nuclear translocation within 15 min, which was associated with Atox1 binding to TNF-α receptor-associated factor 4 (TRAF4) in a Cu-dependent manner. TRAF4 depletion by siRNA significantly inhibited Atox1 nuclear translocation, p47phox expression, and ROS production as well as its downstream VCAM1/ICAM1 expression and monocyte adhesion to inflamed ECs, which were rescued by overexpression of nuclear targeted Atox1. Furthermore, Atox1 colocalized with TRAF4 at the nucleus in TNF-α-stimulated inflamed ECs and vessels. In summary, Cu-dependent Atox1 binding to TRAF4 plays an important role in Atox1 nuclear translocation and ROS-dependent inflammatory responses in TNF-α-stimulated ECs. Thus the Atox1-TRAF4 axis is a novel therapeutic target for vascular inflammatory disease such as atherosclerosis.
MicroRNA-mediated downregulation of K+ channels in pulmonary arterial hypertension
Authors: Babicheva Aleksandra , Ayon Ramon J. , Zhao Tengteng , Ek Vitorin Jose F. , Pohl Nicole M. , Yamamura Aya , Yamamura Hisao , Quinton Brooke A. , Ba Manqing , Wu Linda , Ravellette Keeley S. , Rahimi Shamin , Balistrieri Francesca , Harrington Angela , Vanderpool Rebecca R. , Thistlethwaite Patricia A. , Makino Ayako , Yuan Jason X.-J.
Published: September 2019

Downregulated expression of K+ channels and decreased K+ currents in pulmonary artery smooth muscle cells (PASMC) have been implicated in the development of sustained pulmonary vasoconstriction and vascular remodeling in patients with idiopathic pulmonary arterial hypertension (IPAH). However, it is unclear exactly how K+ channels are downregulated in IPAH-PASMC. MicroRNAs (miRNAs) are small non-coding RNAs that are capable of posttranscriptionally regulating gene expression by binding to the 3′-untranslated regions of their targeted mRNAs. Here, we report that specific miRNAs are responsible for the decreased K+ channel expression and function in IPAH-PASMC. We identified 3 miRNAs (miR-29b, miR-138, and miR-222) that were highly expressed in IPAH-PASMC in comparison to normal PASMC (>2.5-fold difference). Selectively upregulated miRNAs are correlated with the decreased expression and attenuated activity of K+ channels. Overexpression of miR-29b, miR-138, or miR-222 in normal PASMC significantly decreased whole cell K+ currents and downregulated voltage-gated K+ channel 1.5 (KV1.5/KCNA5) in normal PASMC. Inhibition of miR-29b in IPAH-PASMC completely recovered K+ channel function and KV1.5 expression, while miR-138 and miR-222 had a partial or no effect. Luciferase assays further revealed that KV1.5 is a direct target of miR-29b. Additionally, overexpression of miR-29b in normal PASMC decreased large-conductance Ca2+-activated K+ (BKCa) channel currents and downregulated BKCa channel β1 subunit (BKCaβ1 or KCNMB1) expression, while inhibition of miR-29b in IPAH-PASMC increased BKCa channel activity and BKCaβ1 levels. These data indicate upregulated miR-29b contributes at least partially to the attenuated function and expression of KV and BKCa channels in PASMC from patients with IPAH.
Influence of kinesthetic motor imagery and effector specificity on the long-latency stretch response
Authors: Forgaard Christopher J. , Franks Ian M. , Maslovat Dana , Chua Romeo
Published: September 2019

The long-latency “reflexive” response (LLR) following an upper limb mechanical perturbation is generated by neural circuitry shared with voluntary control. This feedback response supports many task-dependent behaviors and permits the expression of goal-directed corrections at latencies shorter than voluntary reaction time. An extensive body of literature has demonstrated that the LLR shows flexibility akin to voluntary control, but it has not yet been tested whether instruction-dependent LLR changes can also occur in the absence of an overt voluntary response. The present study used kinesthetic motor imagery ( experiment 1) and instructed participants to execute movement with the unperturbed contralateral limb ( experiment 2) to explore the relationship between the overt production of a voluntary response and LLR facilitation. Activity in stretched right wrist flexors were compared with standard “do not-intervene” and “compensate” conditions. Our findings revealed that on ~40% of imagery and ~50% of contralateral trials, a response occurred during the voluntary epoch in the stretched right wrist flexors. On these “leaked” trials, the early portion of the LLR (R2) was facilitated and displayed a similar increase to compensate trials. The latter half of the LLR (R3) showed further modulation, mirroring the patterns of voluntary epoch activity. By contrast, the LLR on “non-leaked” imagery and contralateral trials did not modulate. We suggest that even though a hastened voluntary response cannot account for all instruction-dependent LLR modulation, the overt execution of a response during the voluntary epoch in the same muscle(s) as the LLR is a prerequisite for instruction-dependent facilitation of this feedback response.

NEW & NOTEWORTHY Using motor imagery and contralateral responses, we provide novel evidence that facilitation of the long-latency reflex (LLR) requires the execution of a response during the voluntary epoch. A high proportion of overt response “leaks” were found where the mentally simulated or mirrored response appeared in stretched muscle. The first half of the LLR was categorically sensitive to the appearance of leaks, whereas the latter half displayed characteristics closely resembling activity in the ensuing voluntary period.
Preferential activation of spinal sensorimotor networks via lateralized transcutaneous spinal stimulation in neurologically intact humans
Authors: Calvert Jonathan S. , Manson Gerome A. , Grahn Peter J. , Sayenko Dimitry G.
Published: September 2019

Transcutaneous spinal stimulation (TSS), a noninvasive technique to modulate sensorimotor circuitry within the spinal cord, has been shown to enable a wide range of functions that were thought to be permanently impaired in humans with spinal cord injury. However, the extent to which TSS can be used to target specific mediolateral spinal cord circuitry remains undefined. We tested the hypothesis that TSS applied unilaterally to the skin ~2 cm lateral to the midline of the lumbosacral spine selectively activates ipsilateral spinal sensorimotor circuitry, resulting in ipsilateral activation of downstream lower extremity neuromusculature. TSS cathodes and anodes were positioned lateral from the midline of the spine in 15 healthy subjects while supine, and the timing of TSS pulses was synchronized to recordings of lower extremity muscle activity and force. At motor threshold, left and right TSS-evoked muscle activity was significantly higher in the ipsilateral leg compared with contralateral recordings from the same muscles. Similarly, we observed a significant increase in force production in the ipsilateral leg compared with the contralateral leg. Delivery of paired TSS pulses, during which an initial stimulus was applied to one side of the spinal cord and 50 ms later a second stimulus was applied to the contralateral side, revealed that ipsilateral leg muscle responses decreased following the initial stimulus, whereas contralateral muscle responses did not decrease, indicating side-specific activation of lateral spinal sensorimotor circuitry. Our results indicate TSS can selectively engage ipsilateral neuromusculature via lumbosacral sensorimotor networks responsible for lower extremity function in healthy humans.

NEW & NOTEWORTHY We demonstrate the selectivity of transcutaneous spinal stimulation (TSS), which has been shown to enable function in humans with chronic paralysis. Specifically, we demonstrate that TSS applied to locations lateral to the spinal cord can selectively activate ipsilateral spinal sensorimotor networks. We quantified lumbosacral spinal network activity by recording lower extremity muscle electromyography and force. Our results suggest lumbosacral TSS engages side-specific spinal sensorimotor networks associated with ipsilateral lower extremity function in humans.
Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression?
Authors: Caulfield Kevin A.
Published: September 2019

A recent study by Williams et al. (Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. Brain 141: e18, 2018) used accelerated, high-dose intermittent theta burst stimulation (iTBS) to treat highly treatment-resistant depression patients. Remarkably, most patients remitted, but the durability of therapeutic response was weak and all patients relapsed within 2 wk posttreatment. This mini-review examines the “fast on, fast off” effects of accelerated, high-dose iTBS for depression and suggests a new treatment that would combine the strengths of multiple extant iTBS protocols.
Governance of Relationship Risks in Megaprojects: A Social Network Analysis
Authors: Xie Linlin , Han Ting , Skitmore Martin
Published: September 2019

Megaprojects usually involve an alarmingly large number of stakeholders that form a complicated social network and lead to significant relationship risks to client/owners. Therefore, it is necessary to carry out megaproject risk management from a sociological point of view. Based on a case study of the Zhuhai Port, which connects Hong Kong, Zhuhai, and Macao, this paper analyzes the relationship risk between stakeholders and corresponding risk management strategies using social network analysis (SNA). The findings show that stakeholders with a lower density and higher centrality in the network have comparatively a lower relationship risk. Different stakeholders should choose appropriate partners to improve their centrality, reduce the network density to increase their ability to access resources, and enhance their influence and independence in the network. For megaproject client/owners, identifying and monitoring key stakeholders is the key to effective relationship risk governance. The findings provide a number of practical implications for relationship risk management and further demonstrate the importance of stakeholder teamwork, particularly for megaprojects.
Synthesis of Some New 1,2,4-Triazine and 1,2,5-Oxadiazine Derivatives with Antimicrobial Activity
Authors: Hashem Heba E. , Abo-Bakr Ahmed M.
Published: September 2019

1,2,4-Triazine and 1,2,5-oxadiazine derivatives2–12were obtained from treated 1,3-oxazolone (1) with phenyl hydrazine or hydroxylamine hydrochloride. Chlorotriazine derivative3undergoing condensation reactions with different reagents produced new fused tetrazolo-triazine and triazino-quinazolinone derivatives. 1,2,5-Oxadiazine has been used as a synthon for the fused pyrazolo-oxadiazine derivative. The constitution of the prepared compounds was built up based on microanalytical and spectral data. Some of the new compounds were assessed for their antimicrobial activity.
Prediction of Preterm Birth by Maternal Characteristics and Medical History in the Brazilian Population
Authors: Damaso Enio Luis , Rolnik Daniel Lober , Cavalli Ricardo de Carvalho , Quintana Silvana Maria , Duarte Geraldo , da Silva Costa Fabricio , Marcolin Alessandra
Published: September 2019

Objectives. The aim of this study was to assess the performance of a previously published algorithm for first-trimester prediction of spontaneous preterm birth (PTB) in a cohort of Brazilian women. Methods. This was a retrospective cohort study of women undergoing routine antenatal care. Maternal characteristics and medical history were obtained. The data were inserted in the Fetal Medicine Foundation (FMF) online calculator to estimate the individual risk of PTB. Univariate and multivariate logistic regression analyses were performed to determine the effects of maternal characteristics on the occurrence of PTB. A receiver-operating characteristics (ROC) curve was used to determine the detection rates and false-positive rates of the FMF algorithm in predicting PTB <34 weeks of gestation in our population. Results. In total, 1,323 women were included. Of those, 23 (1.7%) had a spontaneous PTB before 34 weeks of gestation, 87 (6.6%) had a preterm birth between 34 and 37 weeks, and 1,197 (91.7%) had a term delivery. Smoking and a previous history of recurrent PTB between 16 and 30 weeks of gestation without prior term pregnancy were significantly more common among women who delivered before 34 weeks of gestation compared to those who delivered at term were (39.1% vs. 12.0%, p=0.001 and 8.7% vs. 0%, p<0.001, respectively). Smoking and history of spontaneous PTB remained significantly associated with spontaneous PTB in the multivariate logistic regression analysis. Significant prediction of PTB <34 weeks of gestation was provided by the FMF algorithm (area under the ROC curve 0.67, 95% CI 0.56–0.78, p=0.005), but the detection rates for fixed false-positive rates of 10% and 20% were poor (26.1% and 34.8%, respectively). Conclusions. Maternal characteristics and history in the first trimester can significantly predict the occurrence of spontaneous delivery before 34 weeks of gestation. Although the predictive algorithm performed similarly to previously published data, the detection rates are poor and research on new biomarkers to improve its performance is needed.
Influence Factors on the Hepatotoxicity ofPolygoni Multiflori Radix
Authors: Wei Yun , Liu Meixia , Liu Jiangang , Li Hao
Published: September 2019

Background. Chinese herbal medicine (CHM) with reported hepatotoxicity is identified, in whichPolygoni Multiflori Radix(HSW) attracts most attention. According to the Traditional Chinese Medicine (TCM) theory, processing is believed to be able to reduce the toxicity of HSW, but in publications, both processed and unprocessed HSW are reported to cause liver injury.Methods. This article reviews the case reports and experimental researches involving liver damage associated with HSW from the following aspects: clinical features, hepatic toxicity components, hepatotoxicity mechanism, and so on.Results. HSW has hepatotoxicity in different degrees and even leads to death, and the reason is multioriginal.Conclusions. People should be educated to have a broad understanding on ensuring drug use safety and lower drug-induced risks when taking HSW preparations.
Effect of Blending Degree between Virgin and Aged Binder on Pavement Performance of Recycled Asphalt Mixture with High RAP Content
Authors: Xu Ying , Chou Zhijing , Li Yunze , Ji Jie , Xu Shi-fa
Published: September 2019

In this study, the influence of the blending degree between virgin and aged binder on the pavement performance of hot-mix recycled asphalt mixture (HMRAM) with high RAP content is analyzed. The aggregate gradation of AC-16 was selected. The RAP contents were 30, 40, and 50%. HMRAMs with different degrees of blending (DOBs) were prepared by changing the mixing temperature (150, 165, and 180°C) without the occurrence of excessive aging for asphalt binders. An improved Hirsch dynamic modulus prediction model was then used to quantitatively characterize the DOB of HMRAM. Finally, the high-temperature, low-temperature, moisture stability, and fatigue resistance performance of HMRAM were tested and the effect of the DOB between the virgin and aged asphalt binder on the pavement performance was analyzed. The results showed that the DOB between the virgin and aged asphalt binder cannot reach 100% at the three mixing temperatures for HMRAM with 30, 40, and 50% RAP contents, which is inconsistent with the assumption of complete blending in China’s specification. The dynamic stability of the mixture gradually decreases with the increased DOB for HMRAM with a high RAP content, while the moisture stability, low-temperature, and fatigue resistance performance are continuously improved. This means that with the increase in DOB in the stage of open to traffic, meeting high-temperature performance criteria at the design stage may become unsatisfactory for HMRAM. The moisture stability, low-temperature performance, and fatigue resistance performances of HMRAM measured at the design stage were reasonable and conservative. The change in DOB significantly affects the content and properties of total free binder in HMRAM, affecting pavement performance. The content and physical properties of the RAP aggregate also have a significant impact on pavement performance.
Intraocular Pressure Changes during Femtosecond Laser-Assisted Cataract Surgery: A Comparison between Two Different Patient Interfaces
Authors: De Giacinto Chiara , D’Aloisio Rossella , Bova Alessandro , Candian Tommaso , Perrotta Alberto Armando , Tognetto Daniele
Published: September 2019

Purpose. The aim of this retrospective cohort study was to evaluate intraocular pressure (IOP) changes during femtosecond laser-assisted cataract surgery (FLACS) using two different patient interface systems. Methods. 116 eyes of 116 patients scheduled for cataract surgery were divided into 2 groups: group 1 (61 eyes) and group 2 (55 eyes) underwent FLACS using Catalys Laser with fluid interface (liquid optics interface, LOI) and LenSx Laser with curved interface and soft contact lens (SoftFit), respectively. IOP was assessed using a portable rebound tonometer (Icare®) preoperatively, after docking, immediately after surgery, at one and seven days postoperatively. Results. In group 1, the mean IOP (±SD) was 14.1 ± 0.4 mmHg before surgery, 33.2 ± 1.1 mmHg after docking, and 21.4 ± 0.9 mmHg immediately after surgery. In group 2, the mean IOP was 13.8 ± 0.4 mmHg before surgery, 24.2 ± 1.4 mmHg after docking, and 20.2 ± 1.2 mmHg immediately after surgery. After the docking procedure, a statistically significant increase in IOP from the baseline was found in both groups (p<0.001). Moreover, no statistically significant difference in IOP measured at 1 and 7 days postoperatively was observed compared with the preoperative values (p>0.05) using both laser platforms. No intraoperative and postoperative complications were observed. Conclusions. FLACS suction phase resulted in a transient increase of IOP in both groups, especially with the LOI system, and it is probably related to the greater pressure of a suction ring and suction generated through the vacuum, independently from the effect of femtosecond laser itself.
Research on the Degree of Coupling between the Urban Public Infrastructure System and the Urban Economic, Social, and Environmental System: A Case Study in Beijing, China
Authors: Tao ZhiMei
Published: September 2019

The coordinated development of urban public infrastructure system and urban economic, social, and environmental system is an important goal for the integrated management and sustainable development of urban public infrastructure system. This paper constructs a research model of the degree of coupling coordination between urban public infrastructure system and urban economic, social, and environmental system using the analytic network process (ANP), the analytic hierarchy process (AHP), a combination evaluation method based on game theory, and a coupling coordination degree model. Using Beijing data from 2000 to 2016, the degree of coupling coordination between the Beijing urban public infrastructure system and the urban economic, social, and environmental system is empirically analyzed. This study finds that (1) the supply level of Beijing’s urban public infrastructure system has an obvious impact on the degree of coupling coordination between the two systems. (2) The global financial crisis reduced the supply speed of the urban public infrastructure system in Beijing, and put the dynamic coupling state of the two systems in the low‐level symbiosis stage. Beijing needs to improve the supply of urban public infrastructure to support the development of the urban economic, social, and environmental system. (3) Improving the supply level of the urban environmental infrastructure in Beijing, especially improving sewage disposal capacity and increasing the number of special vehicles for urban sanitation and the amount of domestic waste clearance, will positively affect the degree of coupling coordination between two systems. (4) An increase in the GDP of Beijing has a direct positive impact on the degree of coupling coordination. In addition, the increase in the social development level of the employees in three industries in Beijing has a significant impact on the degree of coupling coordination.
An Efficient Laguerre-Based FDTD Iterative Algorithm in 3D Cylindrical Coordinate System
Authors: Zhu Da-Wei , Chen Hai-Lin , Pan Zi-Yu , Xu Bo-Ao , Chen Bin
Published: September 2019

Here an efficient Laguerre-based finite-difference time-domain iterative algorithm is proposed. Different from the previously developed iterative procedure used in the efficient FDTD algorithm, a new perturbation term combined with the Gauss–Seidel iterative procedure is introduced to form the new Laguerre-based FDTD algorithm in the 3D cylindrical coordinate system. Such a treatment scheme can reduce the splitting error to a low level and obtain a good convergence; in other words, it can improve the efficiency and accuracy than other algorithms. To verify the performance of the proposed algorithm, two scattering numerical examples are given. The computation results show that the proposed algorithm can be better than the ADI-FDTD algorithm in terms of efficiency and accuracy. Meanwhile, the proposed algorithm is extremely useful for the problems with fine structures in the 3D cylindrical coordinate system.
Scutellarin Suppresses Patient-Derived Xenograft Tumor Growth by Directly Targeting AKT in Esophageal Squamous Cell Carcinoma
Authors: Liu Feifei , Zu Xueyin , Xie Xiaomeng , Zhang Yuanyuan , Liu Kangdong , Chen Hanyong , Wang Ting , Bode Ann M. , Dong Zigang , Kim Dong Joon
Published: September 2019

Scutellarin is a flavonoid compound that is found in Scutellaria barbata. It has been reported to exhibit anticancer and anti-inflammation activities. However, the anticancer properties of scutellarin and its molecular targets have not been investigated in esophageal squamous cell carcinoma (ESCC). In the current study, we report that scutellarin is a potential AKT inhibitor that suppresses patient-derived xenograft ESCC tumor growth. To identify possible molecular targets of scutellarin, potential candidate proteins were screened by an in vitro kinase assay and Western blotting. We found that scutellarin directly binds to the AKT1/2 proteins and inhibits activities of AKT1/2 in vitro. The AKT protein is activated in ESCC tissues and knockdown of AKT significantly suppresses growth of ESCC cells. Scutellarin significantly inhibits anchorage-dependent and independent cell growth and induces G2 phase cell-cycle arrest in ESCC cells. The inhibition of cell growth by scutellarin is dependent on the expression of the AKT protein. Notably, scutellarin strongly suppresses patient-derived xenograft ESCC tumor growth in an in vivo mouse model. Taken together, our data suggest that scutellarin is a novel AKT inhibitor that may prevent progression of ESCC.
Comparison of Systemic Exposure to Toxic and/or Carcinogenic Volatile Organic Compounds (VOC) during Vaping, Smoking, and Abstention
Authors: St. Helen Gideon , Liakoni Evangelia , Nardone Natalie , Addo Newton , Jacob Peyton , Benowitz Neal L.
Published: September 2019

Comparisons of systemic exposure to toxicants during monitored cigarette smoking, electronic cigarette (e-cigarette) use, and abstention are needed to enhance our understanding of the risks of e-cigarette use (vaping). In a cross-over study, we measured 10 mercapturic acid metabolites of volatile organic compounds (VOCs) in 24-hour urine samples collected from 36 dual users (8 women) of e-cigarettes and cigarettes during 2 days of ad libitum vaping or cigarette-only use, and 2 days of enforced abstention. Concentrations of VOC metabolites were higher during smoking compared with vaping, except for the methylating agents' metabolite. The fold-difference in concentrations when smoking relative to vaping ranged from 1.31 (1.06–1.61; geometric mean, 95% confidence interval; 1,3-butadiene) to 7.09 (5.88–8.54; acrylonitrile). Metabolites of acrylamide [fold difference of 1.21 (1.03–1.43)] and benzene [1.46 (1.13–1.90)] were higher during vaping compared with abstention. The 1,3-butadiene and propylene oxide metabolites were higher in variable-power tank users compared with users of cig-a-likes. E-cigarettes expose users to lower levels of toxic VOCs compared with cigarette smoking, supporting their harm reduction potential among smokers. However, some e-cigarettes expose users to VOCs such as acrylamide, benzene, and propylene oxide, and may pose health risks to nonsmoking users. The results of our study will inform regulators in assessing e-cigarettes with respect to the balance between its potential harm reduction for adult smokers and risk to nonsmoking users.
Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11
Authors: Lang Xueting , Green Michael D. , Wang Weimin , Yu Jiali , Choi Jae Eun , Jiang Long , Liao Peng , Zhou Jiajia , Zhang Qiang , Dow Ania , Saripalli Anjali L. , Kryczek Ilona , Wei Shuang , Szeliga Wojciech , Vatan Linda , Stone Everett M. , Georgiou George , Cieslik Marcin , Wahl Daniel R. , Morgan Meredith A. , Chinnaiyan Arul M. , Lawrence Theodore S. , Zou Weiping
Published: September 2019

A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy.

Significance:

This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy.

This article is highlighted in the In This Issue feature, p. 1631
Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury
Authors: Zhang Wen , Yang Yunwen , Gao Huiping , Zhang Yue , Jia Zhanjun , Huang Songming
Published: September 2019

Background: Some researches revealed that mitochondrial dysfunction is associated with various kidney injury. However, the role of mitochondrial dysfunction in the pathogenesis of acute kidney injury (AKI) still needs evidence. Methods: We evaluated the effect of mitochondrial complex I inhibitor rotenone on folic acid (FA)-induced AKI in mice. Results: Strikingly, the mice pretreated with rotenone at a dose of 200 ppm in food showed exacerbated kidney injury as shown by higher levels of blood urea nitrogen and creatinine compared with FA alone group. Meanwhile, both renal tubular injury score and the expression of renal tubular injury marker neutrophil gelatinase-associated lipocalin were further elevated in rotenone-pretreated mice, suggesting the deteriorated renal tubular injury. Moreover, the decrements of mitochondrial DNA copy number and the expressions of mitochondrial Cytochrome c oxidase subunit 1, mitochondrial NADH dehydrogenase subunit 1, and mitochondria-specific superoxide dismutase (SOD2) in the kidneys of FA-treated mice were further reduced in rotenone-pretreated mice, indicating the aggravated mitochondrial damage. In parallel with the SOD2 reduction, the oxidative stress markers of malondialdehyde and HO-1 displayed greater increment in AKI mice with rotenone pretreatment in line with the deteriorated apoptotic response and inflammation. Conclusion: Our results suggested that the inhibition of mitochondrial complex I activity aggravated renal tubular injury, mitochondrial damage, oxidative stress, cell apoptosis, and inflammation in FA-induced AKI.
Inflammation and the Alteration of B-Cell Physiology in Aging
Authors: Hagen Magdalena , Derudder Emmanuel
Published: September 2019

Aging results for the immune system in a departure from the optimal homeostatic state seen in young organisms. This divergence regrettably contributes to a higher frequency of compromised responses to infections and inefficient classical vaccination in aged populations. In B cells, the cornerstone of humoral immunity, the development and distribution of the various mature B cell subsets are impacted by aging in both humans and mice. In addition, aged mature B cells demonstrate limited capacity to mount efficient antibody responses. An expected culprit for the decline in effective immunity is the rise of the systemic levels of pro-inflammatory molecules during aging, establishing a chronic low-grade inflammation. Indeed, numerous alterations affecting directly or indirectly B cells in old people and mice are reminiscent of various effects of acute inflammation on this cell type in young adults. The present mini-review will highlight the possible adverse contributions of the persistent low-level inflammation observed in susceptible older organisms to the inadequate B-cell physiology.
Early Colon Cancer Recurring as Liver Metastasis without Local Recurrence Three Years after Complete Endoscopic Mucosal Resection
Authors: Jeon Min Ho , Jang Sung Wook , Lee Chang Min , Kim Seok Bae
Published: September 2019

Early colon cancer is defined as colon cancer that invades mucosal or submucosal layer regardless of lymph node invasion. Endoscopic mucosal resection can effectively remove early colon cancer which has no lymph node metastasis. Especially, pedunculated polyp has higher complete resection rate and lower recurrence rate that rarely needs additional surgical treatment than sessile polyp. Hence, it is common to follow up without additional treatment after complete resection of pedunculated polyp. We report a case of early colon cancer recurring as liver metastasis 3 years after complete endoscopic mucosal resection.
DNA Variant in the RPGRIP1L Gene Influences Alternative Splicing
Authors: Reble Emma , Feng Yu , Wigg Karen G. , Barr Cathy L.
Published: September 2019

The retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) gene encodes a ciliary protein that is critical for processes related to brain development, including development of left-right asymmetry, sonic hedgehog signaling, and neural tube formation. RPGRIP1L is a risk factor for retinal degeneration, and rare, deleterious variants in the RPGRIP1L gene cause Joubert syndrome and Meckel syndrome, both autosomal recessive disorders. These syndromes are characterized by dysfunctional primary cilia that result in abnormal development – and even lethality in the case of Meckel syndrome. Genetic studies have also implicated RPGRIP1L in psychiatric disorders by suggestive findings from genome-wide association studies and findings from rare-variant exome analyses for bipolar disorder and de novo mutations in autism. In this study we identify a common variant in RPGRIP1L, rs7203525, that influences alternative splicing, increasing the inclusion of exon 20 of RPGRIP1L. We detected this alternative splicing association in human postmortem brain tissue samples and, using a minigene assay combined with in vitro mutagenesis, confirmed that the alternative splicing is attributable to the alleles of this variant. The predominate RPGRIP1L isoform expressed in adult brains does not contain exon 20; thus, a shift to include this exon may impact brain function.