bluuebunny/crossref_metadata_2025 huggingface dataset:
Technological and Human Factors of Malware Attacks
Authors: Lévesque Fanny Lalonde , Chiasson Sonia , Somayaji Anil , Fernandez José M.
Published: July 2018

The success (or failure) of malware attacks depends upon both technological and human factors. The most security-conscious users are susceptible to unknown vulnerabilities, and even the best security mechanisms can be circumvented as a result of user actions. Although there has been significant research on the technical aspects of malware attacks and defence, there has been much less research on how users interact with both malware and current malware defences.

This article describes a field study designed to examine the interactions between users, antivirus (AV) software, and malware as they occur on deployed systems. In a fashion similar to medical studies that evaluate the efficacy of a particular treatment, our experiment aimed to assess the performance of AV software and the human risk factors of malware attacks. The 4-month study involved 50 home users who agreed to use laptops that were instrumented to monitor for possible malware attacks and gather data on user behaviour. This study provided some very interesting, non-intuitive insights into the efficacy of AV software and human risk factors. AV performance was found to be lower under real-life conditions compared to tests conducted in controlled conditions. Moreover, computer expertise, volume of network usage, and peer-to-peer activity were found to be significant correlates of malware attacks. We assert that this work shows the viability and the merits of evaluating security products, techniques, and strategies to protect systems through long-term field studies with greater ecological validity than can be achieved through other means.
Transitional Justice and Economic Policy
Authors: Urueña René , Prada-Uribe María Angélica
Published: July 2018

The field of transitional justice has faced several challenges in its relatively short life span. The latest of these challenges is the claim for broadening its scope to incorporate social justice– and development-related matters. And in just a few years, the possibility and adequacy of thicker or more holistic conceptions of transitional justice have become mainstream. Nonetheless, since their beginnings these new approaches have been subject to criticism from both within and outside the field. This article describes the trajectory of the scholarly debate on expanding transitional justice to encompass socioeconomic concerns, as well as its main limitations. It starts by exploring the main reasons that led to the historical marginalization of socioeconomic concerns in transitional justice theory and practice. It then considers the rationale for the implementation of broader approaches to transitional justice and closes with a discussion of the main challenges and limitations these proposals face.
Baculovirus Entry and Egress from Insect Cells
Authors: Blissard Gary W. , Theilmann David A.
Published: July 2018

Baculoviruses are large DNA viruses of insects that are highly pathogenic in many hosts. In the infection cycle, baculoviruses produce two types of virions. These virion phenotypes are physically and functionally distinct, and each serves a critical role in the biology of the virus. One phenotype, the occlusion-derived virus (ODV), is occluded within a crystallized protein that facilitates oral infection of the host. A large complex of at least nine ODV envelope proteins called per os infectivity factors are critically important for ODV infection of insect midgut epithelial cells. Viral egress from midgut cells is by budding to produce a second virus phenotype, the budded virus (BV). BV binds, enters, and replicates in most other tissues of the host insect. Cell recognition and entry by BV are mediated by a single major envelope glycoprotein: GP64 in some baculoviruses and F in others. Entry and egress by the two virion phenotypes occur by dramatically different mechanisms and reflect a life cycle in which ODV is specifically adapted for oral infection while BV mediates dissemination of the infection within the animal.
Color Perception: Objects, Constancy, and Categories
Authors: Witzel Christoph , Gegenfurtner Karl R.
Published: July 2018

Color has been scientifically investigated by linking color appearance to colorimetric measurements of the light that enters the eye. However, the main purpose of color perception is not to determine the properties of incident light, but to aid the visual perception of objects and materials in our environment. We review the state of the art on object colors, color constancy, and color categories to gain insight into the functional aspects of color perception. The common ground between these areas of research is that color appearance is tightly linked to the identification of objects and materials and the communication across observers. In conclusion, we argue that research should focus on how color processing is adapted to the surface properties of objects in the natural environment in order to bridge the gap between the known early stages of color perception and the subjective appearance of color.
Proteomics reveals Rictor as a noncanonical TGF-β signaling target during aneurysm progression in Marfan mice
Authors: Parker Sarah J. , Stotland Aleksandr , MacFarlane Elena , Wilson Nicole , Orosco Amanda , Venkatraman Vidya , Madrid Kyle , Gottlieb Roberta , Dietz Harry C. , Van Eyk Jennifer E.
Published: July 2018

The objective of the present study was to 1) analyze the ascending aortic proteome within a mouse model of Marfan syndrome (MFS; Fbn1C1041G/+) at early and late stages of aneurysm and 2) subsequently test a novel hypothesis formulated on the basis of this unbiased proteomic screen that links changes in integrin composition to transforming growth factor (TGF)-β-dependent activation of the rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling pathway. Ingenuity Pathway Analysis of over 1,000 proteins quantified from the in vivo MFS mouse aorta by data-independent acquisition mass spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice. We validated this pattern of Rictor activation in vivo by Western blot analysis for phosphorylation on Thr1135 in a separate cohort of mice and showed in vitro that TGF-β activates Rictor in an integrin-linked kinase-dependent manner in cultured aortic vascular smooth muscle cells. Expression of β3-integrin was upregulated in the aged MFS aorta relative to young MFS mice and wild-type mice. We showed that β3-integrin expression and activation modulated TGF-β-induced Rictor phosphorylation in vitro, and this signaling effect was associated with an altered vascular smooth muscle cell proliferative-migratory and metabolic in vitro phenotype that parallels the in vivo aneurysm phenotype in MFS. These results reveal that Rictor is a novel, context-dependent, noncanonical TGF-β signaling effector with potential pathogenic implications in aortic aneurysm.

NEW & NOTEWORTHY We present the most comprehensive quantitative analysis of the ascending aortic aneurysm proteome in Marfan syndrome to date resulting in novel and potentially wide-reaching findings that expression and signaling by β3-integrin constitute a modulator of transforming growth factor-β-induced rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling and physiology in aortic vascular smooth muscle cells.
The Piezo1 cation channel mediates uterine artery shear stress mechanotransduction and vasodilation during rat pregnancy
Authors: John Liam , Ko Nga Ling , Gokin Alexander , Gokina Natalia , Mandalà Maurizio , Osol George
Published: July 2018

During mammalian pregnancy, the uterine circulation must undergo substantial vasodilation and growth to maintain sufficient uteroplacental perfusion. Although we and others have shown that nitric oxide (NO) is a key mediator of these processes, the mechanisms that augment uterine artery NO signaling during gestation have not been identified. We hypothesized that Piezo1, a recently discovered cation channel, may be involved in the process of shear stress mechanotransduction, as other studies have shown that it is both mechanosensitive and linked to NO production. Surprisingly, there are no studies on Piezo1 in the uterine circulation. Our aims in the present study were to determine whether this novel channel is 1) present in uterine arteries, 2) regulated by gestation, 3) functionally relevant (able to elicit rises in intracellular Ca2+concentration and vasodilation), and 4) linked to NO. Immunohistochemistry confirmed that Piezo1 is present in uterine arteries, primarily but not exclusively in endothelial cells. Western blot analysis showed that its protein expression was elevated during gestation. In pressurized main uterine arteries, pharmacological activation of Piezo1 by Yoda1 produced near maximal vasodilation and was associated with significant increases in intracellular Ca2+concentration in endothelial cell sheets. Shear stress induced by intraluminal flow produced reversible vasodilations that were inhibited >50% by GsMTx-4, a Piezo1 inhibitor, and by Nω-nitro-l-arginine methyl ester/ Nω-nitro-l-arginine, inhibitors of NO synthase. These findings are the first to implicate a functional role for Piezo1 in the uterine circulation as a mechanosensor of endothelial shear stress. Moreover, our data demonstrate that Piezo1 activation leads to vasodilation via NO and indicate that its molecular expression is upregulated during pregnancy.

NEW & NOTEWORTHY This is the first study to highlight Piezo1 in the uterine circulation. As a potentially important endothelial mechanosensor of shear stress, Piezo1 may be linked to mechanisms that support increased uteroplacental perfusion during pregnancy.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/piezo1-mechanotransduction-in-the-uterine-circulation/ .
Mitochondria “THE” target of myocardial conditioning
Authors: Boengler Kerstin , Lochnit Günter , Schulz Rainer
Published: July 2018

Several interventions, such as ischemic preconditioning, remote pre/perconditioning, or postconditioning, are known to decrease lethal myocardial ischemia-reperfusion injury. While several signal transduction pathways become activated by such maneuvers, they all have a common end point, namely, the mitochondria. These organelles represent an essential target of the cardioprotective strategies, and the preservation of mitochondrial function is central for the reduction of ischemia-reperfusion injury. In the present review, we address the role of mitochondria in the different conditioning strategies; in particular, we focus on alterations of mitochondrial function in terms of energy production, formation of reactive oxygen species, opening of the mitochondrial permeability transition pore, and mitochondrial dynamics induced by ischemia-reperfusion.
Complexity Analysis on the Aerodynamic Performance of the Mega High‐Speed Train Caused by the Wind Barrier on the Embankment
Authors: Hu He-xuan , Lei Wan-xin , Zhang Ye
Published: July 2018

With the world development of high‐speed railways and increasing speeds, aerodynamic forces and moments acting on trains have been increased further, making trains stay at a “floated” state. Under a strong crosswind, the aerodynamic performance of a train on the embankment is greatly deteriorated; lift force and horizontal force borne by trains will be increased quickly; trains may suffer derailing or overturning more easily compared with the flat ground; train derailing will take place when the case is serious. All of these phenomena have brought risks to people’s life and properties. Hence, the paper establishes an aerodynamic model about a high‐speed train passing an air barrier, computes aerodynamic forces and moments, and analyzes pulsating pressures on the train surface as well as those of unsteady flow fields around the train. Computational results indicate that when the train passed the embankment air barrier, the head wave of air pressure full wave is more than the tail wave; the absolute value of negative wave is more than that of the positive wave, which is more obvious in the head train. When the train is passing the air barrier, pressure pulsation values at head train points are more than those at other points, while pressure changes most violently at the train bottom, and pressure values close to the air barrier are more than those points far from the air barrier. Pressure values at the cross section 1 were larger than those of other points. Pressure values at measurement points of the tail train ranked the second place, with the maximum negative pressure of 1253 Pa. Pressure change amplitudes and maximum negative pressure on the train surface are increased quickly, while pressure peak values on the high‐speed train surface are in direct ratio to the running speed. With the increased speed of the high‐speed train, when it is running in the embankment air barrier, the aerodynamic force and moment borne by each train body are increased sharply, while the head train suffers the most obvious influences of aerodynamic effects.
Peroxisome Proliferator-Activated Receptor-γPrevents Cholesterol Gallstone Formation in C57bl Mice by Regulating Bile Acid Synthesis and Enterohepatic Circulation
Authors: Wang Gang , Han Tao , Wang ShiJia , Chen Min , Sun Yueming , Fu Zan
Published: July 2018

To investigate the role of the peroxisome proliferator-activated receptor-γ(PPARγ) in the progression of cholesterol gallstone disease (CGD), C57bl/6J mice were randomized to the following groups (n=7/group): L (lithogenic diet, LGD), LM (LGD+pioglitazone), CM (chow diet+pioglitazone), and NC (normal control, chow diet). Gallbladder stones were observed by microscopy. Histological gallbladder changes were assessed. Bile acids (BA) and cholesterol were measured in the serum, bile, and feces. Proteins and mRNA expression of genes involved in BA metabolism and enterohepatic circulation were assessed by western blotting and real-time RT-PCR. PPARγactivation was performed in LO2 cell by lentivirus transfection and in Caco2 cell by PPARγagonist treatment. Downregulation of farnesoid X receptor (FXR) by small interference RNA (siRNA) was performed in L02 cells and Caco2 cells, respectively. Results showed that pharmacological activation of PPARγby pioglitazone prevents cholesterol gallstone formation by increasing biliary BA synthesis and enterohepatic circulation. Activated PPARγinduced the expression of genes involved in enterohepatic circulation and bile acid synthesis (like PCG1α, BSEP, MRP2, MRP3, MRP4, NTCP, CYP7A1, CYP27A1, ASBT, OSTα, and OSTβ). Downregulation of FXR repressed expression of partial genes involved in BA enterohepatic circulation. These findings suggest a new function of PPARγin preventing CGD by handling BA synthesis and transport through a FXR dependent or independent pathway.
Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat Diet
Authors: Lu Yanliu , Du Yimei , Qin Lin , Wu Di , Wang Wei , Ling Lei , Ma Feifei , Ling Hua , Yang Li , Wang Changhong , Wang Zhengtao , Zhou Xumei , He Yuqi
Published: July 2018

Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR‐mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL‐C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL‐C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real‐time PCR. The LC‐MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL‐C levels. The gene expression level of Shp was downregulated while the levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by gypenosides. Indicated by LC‐MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine‐conjugated bile acids while decreasing glycine‐conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD‐fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.
DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Mireles-Canales Martha Paola , González-Chávez Susana Aideé , Quiñonez-Flores Celia Maria , León-López Ever Adán , Pacheco-Tena César
Published: July 2018

Systemic lupus erythematosus (SLE) is a perplexing and potentially severe disease, the pathogenesis of which is yet to be understood. SLE is considered to be a multifactorial disease, in which genetic factors, immune dysregulation, and environmental factors, such as ultraviolet radiation, are involved. Recently, the description of novel genes conferring susceptibility to develop SLE even in their own (monogenic lupus) has raised the interest in DNA dynamics since many of these genes are linked to DNA repair. Damage to DNA induces an inflammatory response and eventually triggers an immune response, including those targeting self-antigens. We review the evidence that indicates that patients with SLE present higher levels of DNA damage than normal subjects do and that several proteins involved in the preservation of the genomic stability show polymorphisms, some of which increase the risk for SLE development. Also, the experience from animal models reinforces the connection between DNA damage and defective repair in the development of SLE-like disease including characteristic features such as anti-DNA antibodies and nephritis. Defining the role of DNA damage response in SLE pathogenesis might be strategic in the quest for novel therapies.
Experimental and Numerical Study of Fatigue Damage Assessment under Combined High and Low Cycle Loading
Authors: Han Chaoshuai , Qu Xianqiang , Ma Yongliang , Shi Dexin
Published: July 2018

This paper studies fatigue damage under combined high and low cycle loading. The interaction of two types of loading will greatly reduce fatigue life of structures. Existing methods usually neglect the minor high cycle loading, which obviously underestimates the total fatigue damage. To solve this problem, four methods are proposed and extended for the case of combined loading. Numerical simulations based on the superposition of two sine waves are performed. Experiments are carried out using “DH36” smooth round‐type specimens. Damage predictions results by four methods are compared to the experimental results. It is concluded that some methods give satisfactory fatigue damage estimations and can be regarded as a safe design tool in engineering application.
Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) Are Distinct Entities with Frequent BRAFV600 Mutations
Authors: Wang Anthony C. , Jones David T.W. , Abecassis Isaac Joshua , Cole Bonnie L. , Leary Sarah E.S. , Lockwood Christina M. , Chavez Lukas , Capper David , Korshunov Andrey , Fallah Aria , Wang Shelly , Ene Chibawanye , Olson James M. , Geyer J. Russell , Holland Eric C. , Lee Amy , Ellenbogen Richard G. , Ojemann Jeffrey G.
Published: July 2018

Desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA) are extremely rare tumors that typically arise in infancy; however, these entities have not been well characterized in terms of genetic alterations or clinical outcomes. Here, through a multi-institutional collaboration, the largest cohort of DIG/DIA to date is examined using advanced laboratory and data processing techniques. Targeted DNA exome sequencing and DNA methylation profiling were performed on tumor specimens obtained from different patients (n = 8) diagnosed histologically as DIG/DIGA. Two of these cases clustered with other tumor entities, and were excluded from analysis. The remaining 16 cases were confirmed to be DIG/DIA by histology and by DNA methylation profiling. Somatic BRAF gene mutations were discovered in 7 instances (43.8%); 4 were BRAFV600E mutations, and 3 were BRAFV600D mutations. Three instances of malignant transformation were found, and sequencing of the recurrence demonstrated a new TP53 mutation in one case, new ATRX deletion in one case, and in the third case, the original tumor harbored an EML4–ALK fusion, also present at recurrence. DIG/DIA are distinct pathologic entities that frequently harbor BRAFV600 mutations. Complete surgical resection is the ideal treatment, and overall prognosis is excellent. While, the small sample size and incomplete surgical records limit a definitive conclusion about the risk of tumor recurrence, the risk appears quite low. In rare cases with wild-type BRAF, malignant progression can be observed, frequently with the acquisition of other genetic alterations.

Implications: DIG/DIA are a distinct molecular entity, with a subset frequently harboring either BRAFV600E or BRAFV600D mutations. Mol Cancer Res; 16(10); 1491–8. ©2018 AACR.
Atrophied Thymus, a Tumor Reservoir for Harboring Melanoma Cells
Authors: Sizova Olga , Kuriatnikov Denis , Liu Ying , Su Dong-Ming
Published: July 2018

Tumor metastatic relapse is the primary cause for cancer-associated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, a central T-cell immune organ, has been suggested to be a premetastatic tumor reservoir for B-lymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell–inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor blood stream–circulating melanoma cells. In addition, a chemotherapy-induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemoresistant state.

Implications: Here, the thymus serves as a premetastatic reservoir for nonlymphoid solid tumor cells during chemotherapy, which could be a novel target of minimal residual disease in antitumor therapy, thus preventing tumor metastatic relapse. Mol Cancer Res; 16(11); 1652–64. ©2018 AACR.
Wenn Geschlechtsverkehr nicht möglich ist: Vorstellung eines internetbasierten Behandlungsprogramms für Genito-Pelvine Schmerz-Penetrationsstörung mit Falldarstellung
Authors: Zarski Anna-Carlotta , Berking Matthias , Hannig Wiebke , Ebert David Daniel
Published: July 2018

Hintergrund: Schwierigkeiten, Geschlechtsverkehr zu haben trotz bestehenden Wunsches, stellen für Frauen mit Genito-Pelviner Schmerz-Penetrationsstörung (GPSPS) eine große Belastung dar. Die Verfügbarkeit spezifischer Therapieangebote für sexuelle Funktionsstörungen bei Frauen ist begrenzt und existierende Therapiemöglichkeiten werden oftmals aus Schamgefühlen nicht in Anspruch genommen. Internetbasierte Behandlungsansätze können einen niedrigschwelligen, anonymen, zeit- und ortsunabhängigen spezialisierten Therapiezugang ermöglichen. Bislang liegt noch kein wissenschaftlich evaluiertes Programm für die Behandlung von GPSPS vor. Das Ziel der vorliegenden Arbeit ist es deshalb, den Therapieleitfaden eines neu entwickelten internetbasierten, begleiteten Behandlungsprogramms für GPSPS (Paivina-Care) vorzustellen sowie exemplarisch die Akzeptanz und Zufriedenheit und den subjektiven Nutzen anhand eines Fallberichtes darzustellen. Methodik: Das Rational und der Therapieleitfaden des Behandlungsprogramms werden vorgestellt. Die Falldarstellung nach der Case Reporting (CARE)-Leitlinie präsentiert eine Patientin mit erfolgreichem Behandlungsverlauf sowie qualitative und quantitative Erfolgsmaße. Ergebnisse: Die Kasuistik zeigt, dass das kognitiv-verhaltenstherapeutische Programm basierend auf Schmerz- und Sexualtherapie unter Einbezug des Partners die GPSPS bei der vorgestellten Patientin erfolgreich behandeln konnte und mit hoher Therapiezufriedenheit Schmerzen und sexualitätsbezogene Ängste und negative Kognitionen reduzieren sowie Geschlechtsverkehr ermöglichen konnte. Derzeit erfolgt eine randomisiert-kontrollierte Wirksamkeitsuntersuchung an 200 Frauen mit GPSPS. Schlussfolgerung: Das internetbasierte Behandlungsprogramm bietet Frauen mit GPSPS eine flexible Behandlungsmöglichkeit, die sie anonym, zeit- und ortsunabhängig nutzen können.
Positiver Effekt von Botoxinjektionen auf Kopfschmerzen - willkommener Nebeneffekt, aber keine primäre Indikation
Authors: Gerber Peter Arne
Published: July 2018

Background: Headache is a common disorder of the nervous system; chronic headache in particular may affect quality of life negatively. The pathophysiology is multifactorial and not completely elucidated. Studies have demonstrated the beneficial effects of botulinum toxin A on chronic migraine headaches, but failed to show the same effect on chronic tension-type headaches. Methods: We present the case of a 32-year-old woman who after receiving cosmetic injections with botulinum toxin A for fine lines of the forehead experienced relief of subclinical tension-type headaches. Conclusions: Although the effect of botulinum toxin A on chronic tension-type headaches is limited, several studies demonstrate its pain-modulating effects, and as such it is worth paying attention to this potential beneficial effect when performing cosmetic injections with botulinum toxin A.
Nomograms of the Fetal Sylvian Fissure and Insular Lobe throughout Gestation: A Multicentric, Ultrasonographic Cross-Sectional Study
Authors: Spinelli Marialuigia , Sica Carmine , Ghezzi Fabio , Cromi Antonella , Surbek Daniel , Raio Luigi
Published: July 2018

Introduction: Anomalies in cortical development are often associated with an adverse outcome, but prenatal diagnosis is often impeded by the limited knowledge about normal sulci biometries throughout fetal brain development. Our aim was to provide two-dimensional ultrasonographical (2D US) nomograms of the depth of the Sylvian fissure (SF) and insular lobe (IL), as well as of the SF ratio throughout gestation in a large number of fetuses. Materials and Methods: This was a prospective cross-sectional study of 329 normal singleton pregnancies. Measurements of the SF, IL, and SF ratio were obtained in a standard transthalamic plane of the fetal head. The SF ratio was defined as SF\SF + IL. All measurements were expressed by regression equations as a function of gestational age (GA) according to the method described by Royston and Wright. The first 38 measurements were repeated twice by 2 examiners to assess the reproducibility through the intraclass correlation coefficient (ICC). Results: A significant correlation was found between GA and SF (r = 0.79; p < 0.0001) as well as IL (r = 0.77; p < 0.0001). Similarly, the SF ratio also showed a significant correlation with GA (r = 0.39; p < 0.0001). When interobserver variability was assessed, ICC was 0.97. Conclusions: Prenatal 2D US measurements of SF and IL as well as the SF ratio may be feasible and reproducible using a standard view of the fetal head. Our nomograms may be used as a reference for assessing cortical development throughout pregnancy.
Preventive Nephrology: The Role of Obesity in Different Stages of Chronic Kidney Disease
Authors: Pommer Wolfgang
Published: July 2018

Background: Obesity is increasing worldwide and has become a nontraditional risk factor in chronic kidney disease (CKD). Summary: Obesity-related nephropathy may aggravate renal complications of the metabolic syndrome and progress to advanced CKD stages, while obesity in early stages of CKD is clearly related to the development of kidney disease. A high body mass index (BMI) in advanced CKD stages and dialysis is an advantage for survival (so called “obesity paradox”). A high lean body to fat mass index indicates a beneficial state of body composition. In contrast, loss of muscle mass with increasing fat mass causes “sarcopenia obesity,” which is related to unfavorable outcomes in renal replacement therapy. Obesity (BMI > 30–35) in renal transplant recipients is associated with a higher risk of complications such as delayed graft function, increased rates of rejection, and graft loss. While conservative management of morbid obesity is failing in most cases, bariatric surgery seems to be an option in some cases to improve renal complications in the early stage of CKD or in transplant candidates. Key Message: In conclusion, obesity is increasingly prevalent among CKD patients. Adequate management with respect to the specific role of obesity in different stages of CKD should be integrated in routine renal care.
Ocular Surface Squamous Neoplasia with Intraocular Extension: Clinical and Ultrasound Biomicroscopic Findings
Authors: Meel Rachna , Dhiman Rebika , Sen Seema , Kashyap Seema , Tandon Radhika , Vanathi Murugesan
Published: July 2018

Purpose: To study the clinical profile, ultrasound biomicroscopy (UBM) findings, and treatment outcome of ocular surface squamous neoplasia with intraocular extension (OSSN-IO). Methods: It was a retrospective case series of 7 eyes of OSSN-IO treated at our center from March 2015 till December 2016. Results: Mean age of presentation was 53 years. Clinical signs of intraocular involvement were evident in 3 cases (43%). In the remaining 4 cases (57%), it was diagnosed on UBM alone. Mean tumor height on UBM was 5.06 mm (6.6 mm for nodular and 3.8 mm for nodulo-ulcerative pattern). Of 7 cases, 2 were managed with exenteration, 4 cases with enucleation + limited excision ± external beam radiotherapy, and 1 was lost to follow-up. Complete regression was noted in 83% cases (5/6) and they remain disease free at a mean follow-up of 23.2 months. One case died of metastasis at 7 months. Histopathological examination showed well- to moderately differentiated tumor in all cases. Conclusions: Use of UBM in high-risk OSSN cases may help pick up IO invasion. Tumors that are at high risk for IO invasion are thick nodular tumors (> 5 mm), tumors with nodular or ulcerative morphology, and those with prior surgical intervention.
Stereotactic Body Radiation Therapy as an Alternative Treatment for Patients with Hepatocellular Carcinoma Compared to Sorafenib: A Propensity Score Analysis
Authors: Bettinger Dominik , Pinato David J. , Schultheiss Michael , Sharma Rohini , Rimassa Lorenza , Pressiani Tiziana , Burlone Michela E. , Pirisi Mario , Kudo Masatoshi , Park Joong Won , Buettner Nico , Neumann-Haefelin Christoph , Boettler Tobias , Abbasi-Senger Nasrin , Alheit Horst , Baus Wolfgang , Blanck Oliver , Gerum Sabine , Guckenberger Mathias , Habermehl Daniel , Ostheimer Christian , Riesterer Oliver , Tamihardja Jörg , Grosu Anca-Ligia , Thimme Robert , Brunner Thomas Baptist , Gkika Eleni
Published: July 2018

Background and Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC. Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland. Medical records were reviewed including laboratory parameters, treatment characteristics and development of adverse events. Propensity score matching was performed to adjust for differences in baseline characteristics. The primary endpoint was overall survival (OS) and progression-free survival. Results: Median OS of SBRT patients was 18.1 (10.3–25.9) months compared to 8.8 (8.2–9.5) in sorafenib patients. After adjusting for different baseline characteristics, the survival benefit for patients treated with SBRT was still preserved with a median OS of 17.0 (10.8–23.2) months compared to 9.6 (8.6–10.7) months in sorafenib patients. SBRT treatment of intrahepatic lesions in patients with extrahepatic metastases was also associated with improved OS compared to patients treated with sorafenib in the same setting (17.0 vs. 10.0 months, p = 0.012), whereas in patients with portal vein thrombosis there was no survival benefit in patients with SBRT. Conclusions: In this retrospective comparative study, SBRT showed superior efficacy in HCC patients compared to patients treated with sorafenib.
Effect of Exercise on Physical Recovery of People with Locked-In Syndrome after Stroke: What Do We Know from the Current Evidence? A Systematic Review
Authors: Law Ying Man , Feng Lan Fang , Liang Qui , Meng Li Jiao , Shen Peng , Yu Shuai Jiang , Pao Wing Yi
Published: July 2018

Introduction: Locked-in syndrome (LIS) results from a brainstem lesion in the pons. Ischemic stroke is the most common etiology of LIS. People with LIS have poor mobility with serious complications due to immobilization. Benefits of exercise after stroke have been widely reported. However, little is known about what and how much exercise should be prescribed for these patients. Objectives: To explore and evaluate the effect of exercise on the physical recovery of people with LIS after stroke. Methods: We searched the following databases (last searched August 2017): EMBASE, MEDLINE, PubMed, CINAHL, AMED, PEDro, Cochrane Central Register of Controlled Trials, REHABDATA, Google Scholar, WANFANG, CNKI, and CQVIP. Handsearching of relevant journals and reference lists was also performed. The Oxford Centre for Evidence-Based Medicine was used to assess the evidence level of the included studies. Results: We identified 5 papers from 207 papers involving 35 cases; 26 cases had various degrees of improvement in physical performance after exercise; 9 cases had no change. Five types of exercises and prescriptions were adopted. Study designs and interventions were heterogeneous. All studies contained mixed rehabilitation interventions. A total of 8 different outcome measurement tools have been reported in the studies. Conclusion: Studies indicate a positive trend of effect of exercise for physical recovery of people with LIS after stroke including the improvement of muscle strength, tone, walking ability, and activity in daily living. Mixed physical exercises were used. The effects were not significant. No adverse event has been reported. The quality of the existing evidence is relatively low since the papers were either case series or case studies. Further studies are needed on exercise types and dosages for better prescriptions for people with LIS after stroke. This may help to extend their lives with better control of the complications and to improve their quality of life.
Psychometric Properties of a Modified KINDL-R Questionnaire for Adolescents and Adults, and Construction of a Brief Version, the KINDL-A(dult)B(rief) Questionnaire, KINDL-AB
Authors: Neuner Bruno , Krampe Henning , McCarthy William J. , Reinke Sarah , Kowalski Dorothee , Clausnizer Hartmut , Shneyder Maria , Rocke Angela , Nowak-Göttl Ulrike
Published: July 2018

Background/Aims: The generic quality of life KINDL-R ­questionnaire is validated for use in children/adolescents ≤16 years. The aim of this cross-sectional investigation was to modify the KINDL-R questionnaire for use in adults and to validate its psychometric properties. Methods: Five items of the KINDL-R questionnaire were adapted and the newly developed KINDL-A(dult) questionnaire administered to 255 patients with hereditary and acquired bleeding disorders (mean age 53 years). Its internal consistency and convergent and divergent construct validity were investigated and confirmatory factor analysis was used to evaluate the latent factor structure. Results: The KINDL-A questionnaire showed satisfactory reliability, varying construct validity, but inconclusive factor structure. The KINDL-AB(rief) was developed by removing half of the items and combining 2 sub-axes. This led to factor loadings between 0.62 and 0.91 and increased overall fit (Goodness of fit > 0.8 and Root Mean Square Error of Approximation, RMSEA, < 0.08). Results were validated in 966 healthy blood donors (mean age 38 years). In this group, the KINDL-AB questionnaire showed factor loadings between 0.43 and 0.77, Goodness of fit > 0.95 and RMSEA < 0.05. Conclusions: The new KINDL-AB suggests sufficient to good psychometric properties in adult patients with hereditary and acquired bleeding disorders.
Is Perfusion MRI without Deconvolution Reliable for Mismatch Detection in Acute Stroke? Validation with 15O-Positron Emission Tomography
Authors: Reimer Johanna , Montag Cornelia , Schuster Alexander , Moeller-Hartmann Walter , Sobesky Jan , Heiss Wolf-Dieter , Zaro-Weber Olivier
Published: July 2018

Background: In acute stroke, the magnetic resonance (MR) imaging-based mismatch concept is used to select patients with tissue at risk of infarction for reperfusion therapies. There is however a controversy if non-deconvolved or deconvolved perfusion weighted (PW) parameter maps perform better in tissue at risk prediction and which parameters and thresholds should be used to guide treatment decisions. Methods: In a group of 22 acute stroke patients with consecutive MR and quantitative positron emission tomography (PET) imaging, non-deconvolved parameters were validated with the gold standard for penumbral-flow (PF) detection 15O-water PET. Performance of PW parameters was assessed by a receiver operating characteristic curve analysis to identify the accuracy of each PWI map to detect the ­upper PF threshold as defined by PET cerebral blood flow <20 mL/100 g/min. Results: Among normalized non-deconvolved parameters, PW-first moment without delay correction (FM without DC) > 3.6 s (area under the curve [AUC] = 0.89, interquartile range [IQR] 0.85–0.94), PW-maximum of the concentration curve (Cmax) < 0.66 (AUC = 0.92, IQR 0.84–0.96) and PW-time to peak (TTP) > 4.0 s (AUC = 0.92, IQR 0.87–0.94) perform significantly better than other non-deconvolved parameters to detect the PF threshold as defined by PET. Conclusions: Non-deconvolved parameters FM without DC, Cmax and TTP are an observer-independent alternative to established deconvolved parameters (e.g., Tmax) to guide treatment decisions in acute stroke.
High-Risk Types of Human Papilloma Virus DNA Testing in Women with False Negative Cytology
Authors: Edblad-Svensson Ann , Silfverdal Lena , Collberg Pia , Tunón Katarina
Published: July 2018

Objective: To determine whether high-risk types of human papilloma virus (hrHPV) DNA testing is reliable for selection patients in need of further investigation with colposcopy in women with increased risk of high-grade cervical lesions as a result of false negative cytology. The secondary objective was to compare the sensitivity of hrHPV testing on self-collected versus physician-collected samples for the detection of histological high-grade cervical intraepithelial neoplasia (CIN2+). Methods: Sixty-three patients identified with a missed abnormality following the re-evaluation of benign cervical cytology were included. A patient-collected and a physician-collected sample for HPV, colposcopy and cervical specimen collection for histology and cytology were performed. Results: The sensitivity of hrHPV testing of physician-collected samples for CIN2+ was 100% (95% CI 82.7–100), and the negative predictive value (NPV) was 100% (95% CI 93.3–100). The sensitivity of the self-sampling device to identify CIN2+ was 84.6% (95% CI 59.1–96.7), and the NPV was 94.4% (95% CI 83.4–98.8). The differences in the sensitivity and NPV between the 2 methods were non-significant. The agreement between the 2 methods regarding the HPV results was good, with a kappa value of 0.74 (95% CI 0.57–0.91). Conclusion: The current findings indicate that physician-collected samples for hrHPV DNA testing may be used as triage for the colposcopy of women with false negative cytology.
Home-Based Care Evolution in Chronic Respiratory Failure between 2001 and 2015 (Antadir Federation Observatory)
Authors: Melloni Boris , Mounier Line , Laaban Jean-Pierre , Chambellan Arnaud , Foret Didier , Muir Jean-François
Published: July 2018

Background: The aetiologies of chronic respiratory failure (CRF) are moving in many western countries. Obesity-Hypoventilation syndrome (OHS) has become one of the most common indications of non-invasive ventilation (NIV) with Chronic Obstructive Pulmonary Diseases (COPD). Long-Term Oxygen Therapy (LTOT) technology is the treatment plan for CRF patients in the new era. Objectives: This study aimed to assess home-based care evolution in CRF patients on LTOT (LTOT) and/or NIV from the ANTADIR observatory. Methods: A computerized database from 14 regional facilities was analysed (30% of French home-treated patients). Patient age, sex, aetiology, home respiratory devices were recorded between 2001 and 2015. Results: By the end of 2015, 12,147 CRF patients received LTOT (40%), NIV (24%), LTOT + NIV (23%), continuous positive airway pressure (CPAP; 11%) or LTOT + CPAP (3%). Between 2001 and 2015, we observed a decrease of LTOT (63–40%) in the benefit of NVI ± LTOT (25–47%). Regarding the aetiology, we note a slight decrease in obstructive disease and a significant increase in restrictive disease, mainly due to OHS. The 10-year survival was better on NIV ± LTOT than on LTOT, for overall patients and for both obstructive and restrictive patients. The 10-year survival was better on NIV ± LTOT than on LTOT (35 vs. 10%, p < 0.05). In COPD patients on LTOT, a switch from conventional to new home devices was observed. Stationary LTOT systems were less prescribed, while portable/transportable ­system, liquid oxygen and self-filling oxygen were increasingly prescribed. Conclusion: Our study confirmed changes in CRF aetiologies and home devices. OHS is now an important indication of NIV. Using new LTOT technologies changed home prescriptions in COPD patients.
Variable Vowel Metaphony in Asturian: An Acoustic Analysis
Authors: Barnes Sonia
Published: July 2018

Background/Aims: Vowel metaphony, a type of vowel harmony observed in Asturian, is characterized by the raising and/or centralization of stressed mid or low vowels in the presence of a high vowel in word-final position. Descriptions of Asturian metaphony have been based on data collected using exclusively auditory judgments. This study is the first to document the phenomenon acoustically. Methods: The data were collected using a word elicitation task and sociolinguistic interviews of 40 speakers from the 2 geographic areas in which metaphony has been observed. Qualitative and quantitative analyses of vocalic distributions were performed. Results: The results of the analyses show that: (1) while metaphony still occurs in Asturian, its implementation is highly variable; (2) metaphonized variants remain distinct from other vowels; and (3) the traditional distinction between 2 areas of metaphony cannot be maintained. Conclusion: This study provides the first acoustic characterization of vowel metaphony in Asturian, offering empirical evidence on which to build theoretical approaches to vowel metaphony.
Management of Coagulopathy during Bleeding and Invasive Procedures in Patients with Liver Failure
Authors: Drolz Andreas , Ferlitsch Arnulf , Fuhrmann Valentin
Published: July 2018

Alterations in hemostasis are a characteristic feature of advanced liver disease. Patients with coagulopathy of advanced liver disease are prone to bleedings and also thromboembolic events. Under stable conditions, cirrhosis patients show alterations in both pro- and anticoagulatory pathways, frequently resulting in a rebalanced hemostasis. This review summarizes current recommendations of management during bleeding and prior to invasive procedures in patients with cirrhosis.
Fibronectin Type III Domain-Containing 5 Attenuates Liver Fibrosis Via Inhibition of Hepatic Stellate Cell Activation
Authors: Zhou Bing , Ling Li , Zhang Feng , Liu Tong-Yan , Zhou Hong , Qi Xiao-Hong , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing
Published: July 2018

Background/Aims: Fibronectin type III domain-containing 5 (FNDC5) protein is involved in the beneficial effects of exercise on metabolism. FNDC5 attenuates hepatic steatosis induced by high fat diet (HFD). Here, we examined the effects of FNDC5 on liver fibrosis and underline mechanisms. Methods: Experiments were carried out on wild-type and FNDC5-/- mice, primary mouse hepatic stellate cells (HSCs) and human hepatic stellate cell line (LX-2). The mice were fed with HFD for 6 months to induce liver fibrosis. Oxidized low density lipoprotein (oxLDL) were used to induce the activation of hepatic stellate cells and fibrosis in mouse HSCs and human LX-2 cells. H&E, Masson’s trichrome staining and Sirius red staining were used for liver sections. Protein and mRNA expressions were evaluated with Western blot and RT-PCR, respectively. Results: FNDC5 deficiency aggravated the HFD-induced liver fibrosis and HSCs activation in mice. It exacerbated the HFD-induced inhibition of AMPK phosphorylation, upregulation of connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β), and deposition of extracellular matrix (ECM) in liver of mice. Administration of FNDC5 attenuated oxLDL-induced AMPK deactivation, HSCs activation, CTGF and TGF-β upregulation and ECM deposition in mouse HSCs. The beneficial effects of FNDC5 on oxLDL-induced AMPK dephosphorylation, HSCs activation and ECM deposition were prevented by the inhibition of AMPK with compound C in human LX-2 cells. However, the effects of FNDC5 on hepatic fibrosis in vivo in this study cannot be distinguished from its effects on adiposity and hepatic steatosis. Conclusions: FNDC5 deficiency aggravates HFD-induced liver fibrosis in mice. FNDC5 plays beneficial roles in attenuating liver fibrosis via AMPK phosphorylation-mediated inhibition of HSCs activation.