bluuebunny/crossref_metadata_2025 huggingface dataset:
Chapter 17 Accretionary orogens reworked in an overriding plate setting during protracted continent–continent collision, Sveconorwegian orogen, southwestern Sweden
Authors: Stephens Michael B. , Wahlgren Carl-Henric
Published: January 2020

The Eastern Segment in the Sveconorwegian orogen, southwestern Sweden, is dominated by 2.0–1.8, 1.7 and 1.5–1.4 Ga crust; and the overlying Idefjorden terrane by 1.6–1.5 Ga crust. Assuming reorganization of a subduction system prior to 1.5–1.4 Ga and applying a sinistral transpressive component of disruption during the subsequent Sveconorwegian orogeny (1.1–0.9 Ga), the Idefjorden terrane is inferred to be indigenous outboard rather than exotic with respect to the continental plate Fennoscandia (Baltica). The geological record then records successive westwards shift of accretionary orogens along a convergent plate boundary for at least 500 million years. Sveconorwegian foreland-younging tectonic cycles at
c.
1.05 (or older)–1.02 Ga (Idefjorden terrane) and at
c.
0.99–0.95 Ga (Eastern Segment) prevailed. Crustal thickening and exhumation during oblique convergence preceded migmatization, magmatic activity and a changeover to an extensional regime, possibly triggered by delamination of continental lithosphere, in each cycle. Convergence after 0.95 Ga involved antiformal doming with extensional deformation at higher crustal levels (Eastern Segment) and continued magmatic activity (Idefjorden terrane). An overriding plate setting is inferred during either accretionary orogeny or, more probably, protracted continent–continent collision. Continuity of the erosional fronts in the Grenville and Sveconorwegian orogens is questioned.
Chapter 1 Introduction to the lithotectonic framework of Sweden and organization of this Memoir
Authors: Stephens Michael B.
Published: January 2020

The solid rock geology of Sweden comprises three principal components: (1) Proterozoic and (locally) Archean rocks belonging to the western part of the Fennoscandian Shield; (2) Phanerozoic and (locally) Neoproterozoic sedimentary cover rocks deposited on top of this ancient crust; and (3) the early to mid-Paleozoic (0.5–0.4 Ga) Caledonide orogen. Earlier compilations have applied different principles for the subdivision of the geology in the Fennoscandian Shield and the Caledonide orogen. A uniform lithotectonic framework has been developed here. Crustal segments affected by orogenesis have been identified and their ages determined by the youngest tectonothermal event. Four ancient mountain belts and six orogenies are preserved. Solid rocks outside the orogens have been assigned to different magmatic complexes or sedimentary successions based on their time of formation and tectonic affiliation. This approach allows relicts of older mountain-building activity to be preserved inside a younger orogen – for example, the effects of the Archean (2.8–2.6 Ga) orogeny inside the 2.0–1.8 Ga Svecokarelian orogen and Paleo–Mesoproterozoic (1.7–1.5 and 1.5–1.4 Ga) mountain-building processes inside the 1.1–0.9 Ga Sveconorwegian orogen. Sweden's five largest mineral districts are addressed in the context of this new lithotectonic framework, which forms the architecture to the contents of the chapters in this Memoir.
A novel approach to evaluating the compaction control of soils
Authors: Shimobe Satoru , Spagnoli Giovanni
Published: January 2020

Soil compaction is an important operation during the construction of road embankments, railway subgrade, earth dams and compacted clay liners for waste disposal. Soil compaction is usually controlled based on the ratio of the dry density of the soil to the soil water content. However, this relationship presents problems in both the laboratory and in the field when using excess compaction energy levels in cohesive soils with a high natural water content, including differences in the compaction energy levels and a reduction in strength as a result of over-compaction. The compaction curve, which considered the compaction energy levels, is usually unknown in the field and the main factors influencing the stiffness and strength of compacted soils are the dry density and the degree of saturation. We show here compaction results for soils in terms of the dry density and degree of saturation and introduce the concept of an optimum compaction line.
Adverse Cardiovascular Effects of Traffic Noise with a Focus on Nighttime Noise and the New WHO Noise Guidelines
Authors: Münzel Thomas , Kröller-Schön Swenja , Oelze Matthias , Gori Tommaso , Schmidt Frank P. , Steven Sebastian , Hahad Omar , Röösli Martin , Wunderli Jean-Marc , Daiber Andreas , Sørensen Mette
Published: January 2020

Exposure to traffic noise is associated with stress and sleep disturbances. The World Health Organization (WHO) recently concluded that road traffic noise increases the risk for ischemic heart disease and potentially other cardiometabolic diseases, including stroke, obesity, and diabetes. The WHO report focused on whole-day noise exposure, but new epidemiological and translational field noise studies indicate that nighttime noise, in particular,is an important risk factor for cardiovascular disease (CVD) through increased levels of stress hormones and vascular oxidative stress, leading to endothelial dysfunction and subsequent development of various CVDs. Novel experimental studies found noise to be associated with oxidative stress–induced vascular and brain damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial and neuronal nitric oxide synthase, and vascular/brain infiltration with inflammatory cells. Noise-induced pathophysiology was more pronounced in response to nighttime as compared with daytime noise. This review focuses on the consequences of nighttime noise.
Advanced glycation end products induce immature angiogenesis in in vivo and ex vivo mouse models
Authors: Chen Lixian , Cui Yun , Li Bingyu , Weng Jie , Wang Weiju , Zhang Shuangshuang , Huang Xuliang , Guo Xiaohua , Huang Qiaobing
Published: January 2020

Proliferative diabetic retinopathy (PDR) is a progressive disease predominantly involving pathological angiogenesis and is characterized by the development of immature, fragile, and easily hemorrhagic new vessels. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play important roles in the progression of diabetic retinopathy. Our previous studies demonstrated that AGEs promoted HUVEC angiogenesis by inducing moesin phosphorylation via RhoA/Rho-associated protein kinase (ROCK) pathway. The aim of this study was to further confirm AGE-induced angiogenesis in vivo and the involvement of RAGE, ROCK, and moesin phosphorylation in this process. We performed the study in an AGE-treated mouse model with various angiogenesis assays in multiple in vivo and ex vivo models. The results demonstrated that AGEs promoted significant neovascularization in whole mount retina and mouse aortic ring of adult and postnatal mice and in Matrigel plug as well, which were consistently accompanied by increased moesin phosphorylation. The increase of AGE-evoked neovascularization and moesin phosphorylation were both attenuated by RAGE knockout or ROCK inhibitor Y27632 administration in mice. We also revealed the pathological characteristics of AGE-promoted angiogenesis by demonstrating the decrease of pericyte coverage and the disarranged endothelial alignment in microvessels. In conclusion, this study provides in vivo evidences that AGEs induce immature angiogenesis by binding to RAGE, activating the RhoA/ROCK signal pathway and inducing moesin phosphorylation.

NEW & NOTEWORTHY Advanced glycation end product (AGE)-induced formation of neovessels and phosphorylation of moesin in retina and aortic ring required AGE receptors. AGEs increased neovessels and the phosphorylation of moesin in retina and aortic ring via RhoA/ROCK pathway. AGE-induced immature angiogenesis in AGE-treated mouse retina and aortic ring. The AGE-RAGE axis and moesin could be candidate targets for overcoming relative diseases.
PKCβ and reactive oxygen species mediate enhanced pulmonary vasoconstrictor reactivity following chronic hypoxia in neonatal rats
Authors: Sheak Joshua R. , Yan Simin , Weise-Cross Laura , Ahmadian Rosstin , Walker Benjimen R. , Jernigan Nikki L. , Resta Thomas C.
Published: January 2020

Reactive oxygen species (ROS), mitochondrial dysfunction, and excessive vasoconstriction are important contributors to chronic hypoxia (CH)-induced neonatal pulmonary hypertension. On the basis of evidence that PKCβ and mitochondrial oxidative stress are involved in several cardiovascular and metabolic disorders, we hypothesized that PKCβ and mitochondrial ROS (mitoROS) signaling contribute to enhanced pulmonary vasoconstriction in neonatal rats exposed to CH. To test this hypothesis, we examined effects of the PKCβ inhibitor LY-333,531, the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL), and the mitochondrial antioxidants mitoquinone mesylate (MitoQ) and (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) on vasoconstrictor responses in saline -perfused lungs (in situ) or pressurized pulmonary arteries from 2-wk-old control and CH (12-day exposure, 0.5 atm) rats. Lungs from CH rats exhibited greater basal tone and vasoconstrictor sensitivity to 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619). LY-333,531 and TEMPOL attenuated these effects of CH, while having no effect in lungs from control animals. Basal tone was similarly elevated in isolated pulmonary arteries from neonatal CH rats compared with control rats, which was inhibited by both LY-333,531 and mitochondria-targeted antioxidants. Additional experiments assessing mitoROS generation with the mitochondria-targeted ROS indicator MitoSOX revealed that a PKCβ-mitochondrial oxidant signaling pathway can be pharmacologically stimulated by the PKC activator phorbol 12-myristate 13-acetate in primary cultures of pulmonary artery smooth muscle cells (PASMCs) from control neonates. Finally, we found that neonatal CH increased mitochondrially localized PKCβ in pulmonary arteries as assessed by Western blotting of subcellular fractions. We conclude that PKCβ activation leads to mitoROS production in PASMCs from neonatal rats. Furthermore, this signaling axis may account for enhanced pulmonary vasoconstrictor sensitivity following CH exposure.

NEW & NOTEWORTHY This research demonstrates a novel contribution of PKCβ and mitochondrial reactive oxygen species signaling to increased pulmonary vasoconstrictor reactivity in chronically hypoxic neonates. The results provide a potential mechanism by which chronic hypoxia increases both basal and agonist-induced pulmonary arterial smooth muscle tone, which may contribute to neonatal pulmonary hypertension.
Layered 3D Printing by Tethered Pyro-Electrospinning
Authors: Coppola Sara , Nasti Giuseppe , Vespini Veronica , Ferraro Pietro
Published: January 2020

Nowadays it is easy to imagine that the exploitation of different additive manufacturing approaches could find use in regenerative medicine and frontiers nanotechnology with a strong interest in the development of in vivo bio-incubators that better replicate the tissue environment. Various electrospinning technologies have been exploited for the fabrication of composite polymeric architectures, where fibers have been used for the construction layer by layer of micro-architectures. Unfortunately, in case of processing biomaterials, the intrinsic factors of the materials could become obstacles when considering such advanced engineering methods. Here, for the first time, we use the pyro-EHD process for the fabrication of layered three-dimensional architectures made using a biodegradable and biocompatible polymer. The proposed approach for layered 3D printing works at mild temperature allowing deposition at high resolution and great flexibility in manufacturing, avoiding high voltage generators, and nozzles. The layered 3D printing, activated by the pyro-electric effect, is discussed and characterized in terms of geometrical features and processing parameters. Different geometries and micro-architecture (wall, square, triangle, and hybrid structures) have been demonstrated and over printing of composite polymer, obtained by mixing multiwall carbon nanotubes and fluorochrome, has been discussed, focusing on the use of a biodegradable and biocompatible polymer.
Determinants of Preterm Birth among Women Who Gave Birth in Amhara Region Referral Hospitals, Northern Ethiopia, 2018: Institutional Based Case Control Study
Authors: Mekuriyaw Abebayehu Melesew , Mihret Muhabaw Shumye , Yismaw Ayenew Engida
Published: January 2020

Background. Preterm birth refers to a birth of a baby before 37 completed weeks of gestation and after fetal viability. It is now the leading cause of new born deaths. Although identifying its common risk factors is mandatory to decrease preterm birth and thereby neonatal deaths, there was a dearth of studies in the study area. Objective. The aim of this study was to identify determinants of preterm birth among women who gave birth in Amhara region referral hospitals, Northwest Ethiopia, 2018. Method. An institutional based case-control study was conducted from September 01 to December 01/2018. A total of 405 mothers (135 cases and 270 controls) were included in the study. Multistage sampling technique was employed. Data were collected using structured questionnaire through face to face interview and checklist via Chart review. Data were entered into Epi Info version 7 and export to Statistical Package for Social Sciences (SPSS) version 20 for analysis. Descriptive statics like mean, frequency and percentage was used to describe the characteristics of participants. Both bivariable and multivariable analyses were carried out. Variable having    p-value <0.05 in binary logistic regression were the candidate for multivariable analyses. Finally, the statistical significance of the study was claimed based on the Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) and its p-value <0.05. Result. The result of multivariable analysis show that mothers with no formal education (AOR = 2.24; 95% CI: 1.28, 3.91), history of abortion (AOR = 2.92; 95% CI: 1.3, 6.4), multiple gestation (AOR = 4.1; 95% CI: 1.7, 9.8), hemoglobin level <11 gm/dl (AOR = 2.75; 95% CI: 1.11, 7.31), premature rupture of membrane (AOR = 6.4; 95% CI: 3.23, 12.7) and pregnancy induced hypertension (AOR = 4.74; 95% CI: 2.49, 9.0) had statistically significant association with experiencing preterm birth. Conclusion and Recommendation. Most of the determinants of preterm birth found to be modifiable. Thus, putting emphasis for prevention of obstetric and gynecologic complications such as anemia, premature rupture of membrane and abortion would decrease the incidence of preterm birth. Moreover, strengthening Information Communication Education about prevention of preterm birth was recommended.
[Retracted] Treatment of Large and Complicated Scalp Defects with Free Flap Transfer
Authors: Chen Fanfan , Ju Hongbin , Huang Anfei , Yi Yongjun , Cao Yongfu , Xie Wei , Wang Xinliang , Fu Guo
Published: January 2020

Background. Large scalp defects, especially those complicated by calvarial defects, titanium mesh exposure, or cerebrospinal fluid (CSF) leak, pose a challenge for the neurosurgeon and plastic surgeon. Here, we describe our experience of reconstructing the complex scalp defect with free flap transfer. Methods. From October 2012 to September 2017, 8 patients underwent free flap transfer for the reconstruction of the scalp or complicated scalp and calvarial defects. Five patients presented with scalp tumor and the other 3 patients with scalp necrosis or ulceration (2 patients with titanium plate exposure). Seven anterolateral thigh flaps and one radial forearm flap were harvested and employed. The clinical data, including defect characteristics, flap type, complications, and outcomes, were recorded and analyzed. Results. Five patients were pathologically diagnosed with malignant tumor, and 3 of them were given further radiotherapy. For the 2 patients with exposure of titanium plate, no titanium plate was removed. For the patient with scalp necrosis after decompressive craniectomy accompanied by CSF leakage, the CSF leak was stopped after reconstruction. The size of the flaps ranged from 3 to 14 cm in width and 4 to 18 cm in length. No flap failure occurred in these cases. From follow‐up to the present, no ulceration or necrosis occurred. Conclusions. Free flap transfer is an ideal method for the reconstruction of large, complicated scalp defects with a one‐stage operation. The anterolateral thigh flap is favored because of its durability, adjustability, water tightness, and infection prevention.
Comparison of Cochlear Implant Magnets and Their MRI Artifact Size
Authors: Todt I. , Guerkov R. , Gehl H. B. , Sudhoff H.
Published: January 2020

Introduction. Recent developments regarding cochlear implant magnets (e.g., a bipolar diametral magnet) and refined surgical techniques (e.g., implant positioning) have had a significant impact on the relation between cochlear implants and MRIs, making the reproducible visibility of cochlea and IAC possible. MRI scanning has changed from a contraindication to a diagnostic tool. Magnet artifact size plays a central role in the visual assessment of the cochlea and IAC. Objective. The aim of this study is to compare the CI magnet‐related maximum artifact sizes of various cochlea implant systems. Materials and Methods. We performed an in vivo measurement of MRI artifacts at 1.5 and 3 Tesla with three cochlear implant magnet systems (AB 3D, Medel Synchrony, and Oticon ZTI). The implant, including the magnet, was positioned with a head bandage 7.0 cm and 120° from the nasion, external auditory canal. We used a TSE T2w MRI sequence on the axial and coronal plains and compared the artifacts in two volunteers for each tesla strength. Results. Intraindividual artifact size differences between the three magnets are smaller than interindividual maximum artifact size differences. 3 T MRI scans, in comparison to 1.5 T MRI scans, show a difference between soft artifact areas. Conclusion. We observed no major difference between maximum implant magnet artifact sizes of the three implant magnet types.
The Implications of Converting a High-Volume Multilane Roundabout into a Turbo Roundabout
Authors: Elhassy Zuhair , Abou-Senna Hatem , Shaaban Khaled , Radwan Essam
Published: January 2020

With the growing number of vehicles utilizing roads in the city of Doha, Qatar, most intersections, particularly multilane roundabouts, have been facing traffic congestion dilemma, where traffic demand exceeds capacity. A new design for multilane roundabouts, known as a rotor turbo roundabout, was considered as an alternative to an existing highly congested multilane roundabout. The new design features spiral roadway markings and raised lane dividers which prevent maneuvering within the roundabout and eliminate cutting-offs and weavings. This design has achieved high capacity and low delay in many European countries. In this study, a traffic simulation program, VISSIM, is used to model the complex traffic operation of both the existing and proposed multilane roundabouts and to replicate the high traffic conditions and aggressive driving behavior prevalent among the Middle East countries. Three different rotor designs were examined in an attempt to have a valid comparison between the two types of roundabouts and to adhere to the standard design of the rotor roundabout without violating its essential features. The proposed designs performed slightly better on the minor approaches and managed to deliver an overall improved LOS compared to the conventional design. Major approaches, however, exhibited an increase in vehicle delay and queue lengths. The results showed that the capacity of the conventional three-lane roundabout was always superior to the capacity of the rotor roundabouts. It was concluded that rotor roundabouts may not be suitable for intersections with high demand volumes exceeding 4500 vehicles per hour, and whenever the traffic flow condition is oversaturated.
A Review of Computer‐Aided Heart Sound Detection Techniques
Authors: Li Suyi , Li Feng , Tang Shijie , Xiong Wenji
Published: January 2020

Cardiovascular diseases have become one of the most prevalent threats to human health throughout the world. As a noninvasive assistant diagnostic tool, the heart sound detection techniques play an important role in the prediction of cardiovascular diseases. In this paper, the latest development of the computer‐aided heart sound detection techniques over the last five years has been reviewed. There are mainly the following aspects: the theories of heart sounds and the relationship between heart sounds and cardiovascular diseases; the key technologies used in the processing and analysis of heart sound signals, including denoising, segmentation, feature extraction and classification; with emphasis, the applications of deep learning algorithm in heart sound processing. In the end, some areas for future research in computer‐aided heart sound detection techniques are explored, hoping to provide reference to the prediction of cardiovascular diseases.
Influence of Rosemary Extract Addition in Different Phases on the Oxidation of Lutein and WPI in WPI-Stabilized Lutein Emulsions
Authors: Xu Duoxia , Hou Zhanqun , Liu Guorong , Cao Yanping , Panya Atikorn , Xiao Hang , Dixon Will
Published: January 2020

The aim was to investigate rosemary extract with different addition methods affecting the physicochemical stability of WPI-coated lutein emulsions and examine the correlations between lutein degradation and WPI oxidation during storage. First, lutein emulsions containing different concentrations of rosemary extract in the oil phase were prepared. Second, lutein emulsions containing rosemary extract in the oil phase or water phase were studied along with the kinetic reaction of lutein degradation. Moreover, the impact of rosemary extract on the oxidation of WPI and their products was also determined. It was noticed that rosemary extract at 0.05 wt.% exhibited the best protection of lutein. According to the kinetics analysis of lutein degradation, the direct addition of rosemary extract in the oil phase was more suitable for retarding the degradation of lutein in emulsion than the addition in the aqueous phase due to it being partitioned at the interface. Meanwhile, it was revealed that the addition of rosemary extract in the water phase exhibited better inhibition of the WPI oxidation than addition in the oil phase. The understanding of the association and driving forces of rosemary extract in emulsion systems may be useful for the application of rosemary extract in multicomponent food systems.
Attribute-Guard: Attribute-Based Flow Access Control Framework in Software-Defined Networking
Authors: Zhu Xianwei , Chang ChaoWen , Xi Qin , Zuo ZhiBin
Published: January 2020

Software-defined networking (SDN) decouples the control plane from the data plane, offering flexible network configuration and management. Because of this architecture, some security features are missing. On the one hand, because the data plane only has the packet forwarding function, it is impossible to effectively authenticate the data validity. On the other hand, OpenFlow can only match based on network characteristics, and it is impossible to achieve fine-grained access control. In this paper, we aim to develop solutions to guarantee the validity of flow in SDN and present Attribute-Guard, a fine-grained access control and authentication scheme for flow in SDN. We design an attribute-based flow authentication protocol to verify the legitimacy of the validity flow. The attribute identifier is used as a matching field to define a forwarding control. The flow matching based on the attribute identifier and the flow authentication protocol jointly implement fine-grained access control. We conduct theoretical analysis and simulation-based evaluation of Attribute-Guard. The results show that Attribute-Guard can efficiently identify and reject fake flow.
Room Temperature Surface Modification of Ultrathin FeOOH Cocatalysts on Fe2O3 Photoanodes for High Photoelectrochemical Water Splitting
Authors: Wei Yiqing , Liao Aizhen , Wang Lu , Wang Xiaoyong , Wang Dunhui , Zhou Yong , Zou Zhigang
Published: January 2020

An ultrathin FeOOH cocatalyst is deposited on α-Fe2O3 photoanodes in a simple room temperature immersion process for efficient photoelectrochemical (PEC) water splitting. The prepared FeOOH/Fe2O3 photoanode has a photocurrent density of up to 2.4 mA/cm2 at 1.23 V versus reversible hydrogen electrode (RHE), and the photocurrent density is increased by about 160% compared to the bare Fe2O3 of 1.55 mA/cm2. An obvious cathodic shift of the photocurrent onset potential from 0.661 to 0.582 V was also observed, and excellent stability was maintained with almost no deterioration for 5 h. The enhanced PEC performance is attributed to the decrease of the interfacial resistance between electrode and electrolyte and the increase of the injection efficiency of holes in Fe2O3.
Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review
Authors: Pereira-Moreira Ricardo , Muscelli Elza
Published: January 2020

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules.Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance).Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content;in vivohuman studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport.Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.
Influence of Beam‐to‐Column Linear Stiffness Ratio on Failure Mechanism of Reinforced Concrete Moment‐Resisting Frame Structures
Authors: Su Jizhi , Liu Boquan , Xing Guohua , Ma Yudong , Huang Jiao
Published: January 2020

The design philosophy of a strong‐column weak‐beam (SCWB), commonly used in seismic design codes for reinforced concrete (RC) moment‐resisting frame structures, permits plastic deformation in beams while keeping columns elastic. SCWB frames are designed according to beam‐to‐column flexural capacity ratio requirements in order to ensure the beam‐hinge mechanism during large earthquakes and without considering the influence of the beam‐to‐column stiffness ratio on the failure modes of global structures. The beam‐to‐column linear stiffness ratio is a comprehensive indicator of flexural stiffness, story height, and span. This study proposes limit values for different aseismic grades based on a governing equation deduced from the perspective of member ductility. The mathematical expression shows that the structural yielding mechanism strongly depends on parameters such as material strength, section size, reinforcement ratio, and axial compression ratio. The beam‐hinge mechanism can be achieved if the actual beam‐to‐column linear stiffness ratio is smaller than the recommended limit values. Two 1/3‐scale models of 3‐bay, 3‐story RC frames were constructed and tested under low reversed cyclic loading to verify the theoretical analysis and investigate the influence of the beam‐to‐column linear stiffness ratio on the structural failure patterns. A series of nonlinear dynamic analyses were conducted on the numerical models, both nonconforming and conforming to the beam‐to‐column linear stiffness ratio limit values. The test results indicated that seismic damage tends to occur at the columns in structures with larger beam‐to‐column linear stiffness ratios, which inhibits the energy dissipation. The dynamic analysis suggests that considering the beam‐to‐column linear stiffness ratio during the design of structures leads to a transition from a column‐hinge mechanism to a beam‐hinge mechanism.
Proteomic Analysis of CSF from Patients with Leptomeningeal Melanoma Metastases Identifies Signatures Associated with Disease Progression and Therapeutic Resistance
Authors: Smalley Inna , Law Vincent , Wyatt Clayton , Evernden Brittany , Fang Bin , Koomen John M. , Welsh Eric A. , Macaulay Robert J.B. , Forsyth Peter A. , Smalley Keiran S.M.
Published: January 2020

Purpose:

The development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication of the late-stage disease, for which no effective treatments exist. Here, we performed a multi-omics analysis of the cerebrospinal fluid (CSF) from patients with LMM to determine how the leptomeningeal microenvironment shapes the biology and therapeutic responses of melanoma cells.

Experimental Design:

A total of 45 serial CSF samples were collected from 16 patients, 8 of these with confirmed LMM. Of those with LMM, 7 had poor survival (<4 months) and one was an extraordinary responder (still alive with survival >35 months). CSF samples were analyzed by mass spectrometry and incubated with melanoma cells that were subjected to RNA sequencing (RNA-seq) analysis. Functional assays were performed to validate the pathways identified.

Results:

Mass spectrometry analyses showed the CSF of most patients with LMM to be enriched for pathways involved in innate immunity, protease-mediated damage, and IGF-related signaling. All of these were anticorrelated in the extraordinary responder. RNA-seq analysis showed CSF to induce PI3K/AKT, integrin, B-cell activation, S-phase entry, TNFR2, TGFβ, and oxidative stress responses in the melanoma cells. ELISA assays confirmed that TGFβ expression increased in the CSF of patients progressing with LMM. CSF from poorly responding patients conferred tolerance to BRAF inhibitor therapy in apoptosis assays.

Conclusions:

These analyses identified proteomic/transcriptional signatures in the CSF of patients who succumbed to LMM. We further showed that the CSF from patients with LMM has the potential to modulate BRAF inhibitor responses and may contribute to drug resistance.

See related commentary by Glitza Oliva and Tawbi, p. 2083
Treatment of Capillary Hemangioblastoma in Von Hippel-Lindau Disease: Case Report and Online Survey of Treatment Preferences among Experts
Authors: Valdés-Lara Carlos Andrés , Oyervides-Alvarado Jose Arturo , Elizondo-Camacho Juan Manuel , Acón-Ramírez Dhariana , García-Aguirre Jose Gerardo
Published: January 2020

This case report aims to describe the diagnosis, treatment, and evolution of bilateral, asymmetrical retinal capillary hemangioblastomas treated with argon laser and intravitreal anti-vascular endothelial growth factor and also reports the results of an online survey of treatment preferences among retina and vitreous specialists. A previously healthy 23-year-old female presented to our Retina Department complaining of progressive visual loss in her right eye. Visual acuity at admission was 20/300 in her right eye and 20/20 in her left eye. Anterior segment findings were unremarkable and fundoscopy revealed the presence of retinal capillary hemangioblastomas in both eyes. In the right eye, the hemangioblastoma was associated with pronounced exudation and macular edema; in the left eye, the lesion was quiescent. After a complete anamnesis and genetic counseling, Von Hippel-Lindau disease was diagnosed. Treatment with laser photocoagulation was performed on both eyes. One dose of 0.5 mg intravitreal ranibizumab was applied to the right eye. Two months after treatment, the right eye demonstrated improved visual acuity (20/100). Moreover, an important decrease in tumor dimensions and a reduction of vessel tortuosity was seen in both eyes. At 18 months of follow-up, the patient maintains a good visual acuity without recurrence of the treated tumors. Laser treatment should be considered as the primary treatment option for patients with capillary hemangioblastomas with and without exudation and can be combined with intravitreal antiangiogenics if exudation is significant. Inactive smaller lesions without exudation are likely to have an excellent response to laser treatment alone. Management should be individualized since no consensus between experts has been reached.
Clinical Use and Barriers of Thoracic Ultrasound: A Survey of Italian Pulmonologists
Authors: Zanforlin Alessandro , Tursi Francesco , Marchetti Giampietro , Pellegrino Giulia Michela , Vigo Beatrice , Smargiassi Andrea , Inchingolo Riccardo , Centanni Stefano , Gasparini Stefano , Blasi Francesco , Soldati Gino , Sferrazza Papa Giuseppe Francesco ,   AdET Study Group
Published: January 2020

Introduction: Thoracic ultrasound is accurate in the diagnosis of a wide range of respiratory diseases. Yet the extent of its use is unknown. Through a national survey, we aimed to explore the clinical use of thoracic ultrasound and the barriers to the diffusion of the technique in Italy. Methods: Accademia di Ecografia Toracica (AdET) developed a self-administered survey which was sent by email to Italian pulmonologists via national scientific societies and networks. Results: Of the 2010 physicians invited, 514 completed the survey (26% response rate). According to 99% of responders, thoracic ultrasound had a relevant clinical role. Seventy-nine percent of the responders used thoracic ultrasound at least once a month. The main settings were: 53% pulmonology ward, 15% outpatient clinic, 15% interventional pulmonology room, 10% internal medicine ward, 4% respiratory intensive care units, and 9% other. Thoracic ultrasound was primarily used: (1) with both diagnostic and interventional aims (72%), (2) as diagnostic imaging (17%), and (3) as guidance for interventional procedures (11%). The main clinical applications were: (1) diagnosis and management of pleural effusion, (2) pneumothorax, (3) pneumonia, (4) cardiac failure, and (5) acute dyspnea. Twenty-one percent of the responders do not use thoracic ultrasound. The main reported bar­riers were: (1) availability of an ultrasound system (52%), (2) lack of protected time and training (22%), and (3) use of the technique by other specialists (15%). Conclusion: Thoracic ultrasound is widely used by Italian pulmonologists and considered a clinically relevant tool. The availability of dedicated ultrasound systems seems to be a major limit of the use of the technique.
Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy
Authors: Tseng Tai-Chung , Peng Cheng-Yuan , Hsu Yao-Chun , Su Tung-Hung , Wang Chia-Chi , Liu Chun-Jen , Yang Hung-Chih , Yang Wan-Ting , Lin Chia-Hsin , Yu Ming-Lung , Lai Hsueh-Chou , Tanaka Yasuhito , Nguyen Mindie H. , Liu Chen-Hua , Chen Pei-Jer , Chen Ding-Shinn , Kao Jia-Horng
Published: January 2020

Background and Aims: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker correlating with liver fibrosis stages. However, little is known about how it predicts risks of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term antiviral treatment. Materials and Methods: The study contained 2 parts. The first part was to explore whether M2BPGi could be an HCC predictor in 899 CHB patients receiving long-term entecavir therapy. The second part was to validate the findings in an independent cohort of 384 on-treatment CHB patients with more severe liver disease. Results: In the discovery cohort, there were 64 patients developing HCC within an average follow-up of 7.01 years. Our data showed that M2BPGi level was positively associated with HCC development. When stratifying the patients by an M2BPGi level of 1.73 (the third quartile), the high M2BPGi group was shown to have an increased HCC risk compared to the low M2BPGi group with hazard ratio of 5.80 (95% CI 3.50–9.60). Furthermore, we found that the M2BPGi level complements PAGE-B score, a well-validated HCC prediction model, to predict HCC development. Lastly, the cutoff was validated in the independent cohort, especially those with an intermediate PAGE-B score. Conclusions: In CHB patients receiving long-term antiviral treatment, serum M2BPGi level not only serves as an independent HCC predictor but also complements PAGE-B in stratifying HCC risks.
Correlating Adaptive Optics Images to Clinical Findings in Juvenile Macular Dystrophy with Hypotrichosis in Siblings with Homozygous CDH3 Pathogenic Variation
Authors: Nasser Fadi , Kempf Melanie , Kurtenbach Anne , Stöhr Heidi , Weber Bernhard H.F. , Neuhaus Christine , Rating Philipp , Zrenner Eberhart
Published: January 2020

Objective: We report on two German siblings diagnosed with congenital hypotrichosis and juvenile macular dystrophy, an extremely rare syndrome affecting both hair growth and visual functions. Methods: A detailed ophthalmological examination was carried out including fundus examination, visual acuity assessment, visual field determination, color vision testing, and electrophysiology (electroretinography [ERG]). Additionally, fundus photography and autofluorescence imaging (FAF) was performed, along with optical coherence tomography (OCT) and adaptive optics (AO) fundus imaging. Targeted Sanger sequencing and next-generation gene panel sequencing were carried out. Results: Macular dystrophy was evident in the fundus of both patients, as was a central scotoma in the static visual field. The kinetic visual field was normal. The ERG recordings were also normal, but the amplitudes of the multifocal ERG were reduced in the central 4–5° of the retina. The FAF images revealed a large central hypofluorescent area surrounded by a hyperfluorescent ring. The OCT images showed atrophy in the outer layers and tubulations. The AO images depicted a loss of central photoreceptors, as well as severe central atrophy in patient 1. A cone mosaic was observable in the peripheral AO fundus images of both patients. The disrupted cone mosaic on the AO images correlated with the hypofluorescent areas on autofluorescence. DNA testing identified the homozygous, likely pathogenic variant c.1508G>A/p.(Arg503His) (chr16:68719191) in the CDH3 gene. Conclusions: The two siblings revealed hypotrichosis and macular dystrophy in both eyes. The identification of a homozygous CDH3 mutation in each patient confirms the syndromic entity of hypotrichosis with juvenile macular degeneration.
Pseudoxanthoma Elasticum: An Interesting Model to Evaluate Chronic Kidney Disease-Like Vascular Damage without Renal Disease
Authors: D’Marco Luis , Lima-Martínez Marcos , Karohl Cristina , Chacín Maricarmen , Bermúdez Valmore
Published: January 2020

Background: Pseudoxanthoma elasticum (PXE; OMIM 264800) is an inherited multisystem disorder associated with accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and brush membrane in the eye. Carriers exhibit characteristic lesions in the cardiovascular system, and peripheral and coronary arterial disease as well as mitral valvulopathy often present as a cardiovascular feature of this disease. PXE and chronic kidney disease (CKD) share some common patterns in the vascular damage and in therapeutic approaches as well. Summary: To date, treating PXE has focused more on careful follow-up examinations with retinal specialists and cardiologist, avoiding long-term anticoagulation. Like CKD, maintaining a low-calcium diet, increasing dietary magnesium, and administering phosphate binders such as aluminum hydroxide or sevelamer may yield a modest benefit. Recently, 4-phenylbutyrate acid (4-PBA) has demonstrated a maturation of ABCC6 mutant effects into the plasma membrane. Moreover, in a humanized mouse model of PXE, 4-PBA administration restored the physiological function of ABCC6 mutants, resulting in enhanced calcification inhibition and thus a promising strategy for allele-specific therapy of ABCC6-associated calcification disorders. Key Message: Vascular compromise in PXE patients share some components similar to CKD.
Predictive Factors and Clinical Impact of Deep Remission in Celiac Disease
Authors: Silva Marta , Peixoto Armando , Santos Ana Luísa , Costa-Moreira Pedro , Ferreira da Silva Joel , Dias Emanuel , Macedo Guilherme
Published: January 2020

Introduction: The ultimate indicator of adherence to a gluten-free diet is the demonstration of mucosal healing. However, the need for histological reassessment is subject to controversy among “experts”. The aim of this study was to evaluate celiac patients who underwent histological reevaluation after starting a gluten-free diet in order to identify those with histological remission and associated factors. Methods: This retrospective study included patients who agreed to a histological reassessment after apparent clinical and serological remission and reported at least 12 months of diet adherence. In all cases, informed consent was signed for upper endoscopy. Results: A total of 69 patients were included. In 67.9% of cases, the diagnosis was made in the context of “classic” symptomatology, 17% had “nonclassical” presentation, and 15.1% were in latent phase. 69.2% of the diagnoses were initially suspected by serology. Endoscopically, 11.8% of the patients did not present suggestive features macroscopically, and a histological grade of Marsh IIIa–c was observed in 75.5% of all cases. The histological findings were normalized in 37.7%, which was associated with the presence of lower Marsh score values at diagnosis (p = 0.014) and lower DEXA T-score values (p = 0.038). A histological improvement was observed in 55 patients (≥2 grades in 37 cases), which was related to the initial transferrin saturation (p = 0.027) and with higher Marsh scores at diagnosis (p = 0.007). Conclusion: Even under a gluten-free diet, celiac histology normalization is difficult to obtain and appears to be independent of most clinical and serological findings at diagnosis. Patients with less severe histological levels at diagnosis reach remission more easily, but only represent the ­minority of the population.
Deranged Iron Status Evidenced by Iron Deficiency Characterizes Patients with Hidradenitis Suppurativa
Authors: Ponikowska Malgorzata , Matusiak Lukasz , Kasztura Monika , Jankowska Ewa A. , Szepietowski Jacek C.
Published: January 2020

Background: Proinflammatory activation and autoimmune processes underlie the pathophysiology of hidradenitis suppurativa (HS). Iron deficiency (ID) is frequently present in inflammation-mediated chronic diseases, irrespective of anemia. Objectives: We aimed to characterize iron status in patients with HS. Methods: Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor and hepcidin were assessed as the biomarkers of iron status in 74 patients with HS and 44 healthy subjects. ID was defined as ferritin <100 µg/L or ferritin 100–299 µg/L with Tsat <20% (following the definition used in the other studies in chronic disease). Results: Compared with controls, patients with HS demonstrated a deranged iron status as evidenced by decreased levels of ferritin (91 ± 87 vs. 157 ± 99 µg/L), Tsat (21.5 ± 10.8 vs. 42.2 ± 11.7%) and hepcidin (31.3 ± 25.9 vs. 44.2 ± 22.0 ng/mL) (all p < 0.05 vs. controls). There was also a trend toward higher values of soluble transferrin receptor (1.23 ± 0.35 vs. 1.12 ± 0.19 mg/L) (p = 0.09 vs. controls). Disease severity (assessed with the Hidradenitis Suppurativa Severity Index and the 3-degree Hurley scale) did not differentiate iron status biomarkers. ID was present in 75% of HS patients, and its prevalence was not related with disease severity (Hurley I/II/III – 82 vs. 73 vs. 67%). In HS, none of the iron status biomarkers correlated with the levels of interleukin-6 (a marker of proinflammatory activation). Conclusions: The majority of HS patients demonstrate derangements in iron status typical of ID. These abnormalities are neither related to proinflammatory activation nor associated with disease severity. Whether it may have a therapeutic impact needs to be further studied.
A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings
Authors: Ostermann Thomas , Appelbaum Sebastian , Poier Désirée , Boehm Katja , Raak Christa , Büssing Arndt
Published: January 2020

Purpose: We aimed at updating the evidence found in controlled studies addressing general and event-free survival of cancer patients treated with the fermented mistletoe extract Iscador. Methods: The databases Embase, PubMed, CAMbase, Scopus, AMED and Cochrane were searched for clinical studies on cancer patients treated with Iscador. Quality of studies and risk of bias were evaluated according to the Cochrane guidelines and the Newcastle Ottawa Scale. Outcome data were expressed as hazard ratios (HR) and the respective 95% confidence intervals (CI). Meta-analysis was carried out using a random-effects model. Results: Eighty-two controlled studies met the inclusion criteria, of which 32 with 55 strata provided data for extracting HR and CI. The overall HR was 0.59 (95% CI: [0.53; 0.65], p < 0.0001) in favour of Iscador treatment. Heterogeneity of study results was moderate (I2 = 50.9%; p < 0.0001, τ2 = 0.053). Meta-regression did not reveal significant effects of sample size or study design. However, significant differences were found between cancer entities (p < 0.01), with most pronounced effects in cervical (HR = 0.43) and less pronounced effects in lung cancer (HR = 0.84). Conclusions: We found almost identical effects on cancer survival based on a broader database of higher quality. However, none of the studies was blinded and, therefore, there might be risk of performance bias. Implications for cancer survivors are as follows: findings indicate that adjuvant treatment of cancer patients with Iscador can be associated with a better survival.