bluuebunny/crossref_metadata_2025 huggingface dataset:
Two sides of the same coin: session types and game semantics: a synchronous side and an asynchronous side
Authors: Castellan Simon , Yoshida Nobuko
Published: January 2019

Game semantics and session types are two formalisations of the same concept: message-passing open programs following certain protocols. Game semantics represents protocols as games, and programs as strategies; while session types specify protocols, and well-typed π-calculus processes model programs. Giving faithful models of the π-calculus and giving a precise description of strategies as a programming language are two difficult problems. In this paper, we show how these two problems can be tackled at the same time by building an accurate game semantics model of the session π-calculus.

Our main contribution is to fill a semantic gap between the synchrony of the (session) π-calculus and the asynchrony of game semantics, by developing an event-structure based game semantics for synchronous concurrent computation. This model supports the first truly concurrent fully abstract (for barbed congruence) interpretation of the synchronous (session) π-calculus. We further strengthen this correspondence, establishing finite definability of asynchronous strategies by the internal session π-calculus. As an application of these results, we propose a faithful encoding of synchronous strategies into asynchronous strategies by call-return protocols, which induces automatically an encoding at the level of processes. Our results bring session types and game semantics into the same picture, proposing the session calculus as a programming language for strategies, and strategies as a very accurate model of the session calculus. We implement a prototype which computes the interpretation of session processes as synchronous strategies.
An abstract stack based approach to verified compositional compilation to machine code
Authors: Wang Yuting , Wilke Pierre , Shao Zhong
Published: January 2019

A key ingredient contributing to the success of CompCert, the state-of-the-art verified compiler for C, is its block-based memory model, which is used uniformly for all of its languages and their verified compilation. However, CompCert's memory model lacks an explicit notion of stack. Its target assembly language represents the runtime stack as an unbounded list of memory blocks, making further compilation of CompCert assembly into more realistic machine code difficult since it is not possible to merge these blocks into a finite and continuous stack. Furthermore, various notions of verified compositional compilation rely on some kind of mechanism for protecting private stack data and enabling modification to the public stack-allocated data, which is lacking in the original CompCert. These problems have been investigated but not fully addressed before, in the sense that some advanced optimization passes that significantly change the ways stack blocks are (de-)allocated, such as tailcall recognition and inlining, are often omitted.

We propose a lightweight and complete solution to the above problems. It is based on the enrichment of CompCert's memory model with an abstract stack that keeps track of the history of stack frames to bound the stack consumption and that enforces a uniform stack access policy by assigning fine-grained permissions to stack memory. Using this enriched memory model for all the languages of CompCert, we are able to reprove the correctness of the full compilation chain of CompCert, including all the optimization passes. In the end, we get Stack-Aware CompCert, a complete extension of CompCert that enforces the finiteness of the stack and fine-grained stack permissions.

Based on Stack-Aware CompCert, we develop CompCertMC, the first extension of CompCert that compiles into a low-level language with flat memory spaces. Based on CompCertMC, we develop Stack-Aware CompCertX, a complete extension of CompCert that supports a notion of compositional compilation that we call contextual compilation by exploiting the uniform stack access policy provided by the abstract stack.
From fine- to coarse-grained dynamic information flow control and back
Authors: Vassena Marco , Russo Alejandro , Garg Deepak , Rajani Vineet , Stefan Deian
Published: January 2019

We show that fine-grained and coarse-grained dynamic information-flow control (IFC) systems are equally expressive. To this end, we mechanize two mostly standard languages, one with a fine-grained dynamic IFC system and the other with a coarse-grained dynamic IFC system, and prove a semantics-preserving translation from each language to the other. In addition, we derive the standard security property of non-interference of each language from that of the other, via our verified translation. This result addresses a longstanding open problem in IFC: whether coarse-grained dynamic IFC techniques are less expressive than fine-grained dynamic IFC techniques (they are not!). The translations also stand to have important implications on the usability of IFC approaches. The coarse- to fine-grained direction can be used to remove the label annotation burden that fine-grained systems impose on developers, while the fine- to coarse-grained translation shows that coarse-grained systems---which are easier to design and implement---can track information as precisely as fine-grained systems and provides an algorithm for automatically retrofitting legacy applications to run on existing coarse-grained systems.
Health Impact Assessment of Transportation Projects and Policies: Living Up to Aims of Advancing Population Health and Health Equity?
Authors: Cole Brian L. , MacLeod Kara E. , Spriggs Raenita
Published: January 2019

Health impact assessment (HIA) is a forward-looking, evidence-based tool used to inform stakeholders and policy makers about the potential health effects of proposed projects and policies and to identify options for maximizing potential health benefits and minimizing potential harm. This review examines how health equity, a core principle of health impact assessment (HIA), has been operationalized in HIAs conducted in the United States in one sector, transportation. Two perspectives on promoting health equity appear in the broader public health research literature; one aims at reducing disparities in health determinants and outcomes in affected populations, whereas the other focuses on facilitating community participation and self-determination. Variations in how these perspectives are applied in HIA informed our typology of five ways of addressing health equity in HIA. Transportation HIAs commonly included two of these—selecting vulnerable populations for the focus of the HIA and stakeholder engagement, seen in more than 70% of the 96 HIAs reviewed. Fewer than half of the HIAs assessed current health disparities or changes in their distribution. Only 15% of HIAs addressed equity by focusing on capabilities development or empowerment. Routinely assessing and reporting how an HIA aims to address health equity might better manage expectations and could make HIA practitioners and users more conscious of how an HIA can realistically be used to advance health equity.
All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element
Authors: Tamaki Masanori , Tominaga Tatsuya , Fujita Yui , Koezuka Yasuhiko , Ichien Go , Murakami Taichi , Kishi Seiji , Yamamoto Keiichi , Abe Hideharu , Nagai Kojiro , Doi Toshio
Published: January 2019

Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488–11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.
Tobacco smoking induces cardiovascular mitochondrial oxidative stress, promotes endothelial dysfunction, and enhances hypertension
Authors: Dikalov Sergey , Itani Hana , Richmond Bradley , Arslanbaeva Liaison , Vergeade Aurelia , Rahman S. M. Jamshedur , Boutaud Olivier , Blackwell Timothy , Massion Pierre P. , Harrison David G. , Dikalova Anna
Published: January 2019

Tobacco smoking is a major risk factor for cardiovascular disease and hypertension. It is associated with the oxidative stress and induces metabolic reprogramming, altering mitochondrial function. We hypothesized that cigarette smoke induces cardiovascular mitochondrial oxidative stress, which contributes to endothelial dysfunction and hypertension. To test this hypothesis, we studied whether the scavenging of mitochondrial H2O2 in transgenic mice expressing mitochondria-targeted catalase (mCAT) attenuates the development of cigarette smoke/angiotensin II-induced mitochondrial oxidative stress and hypertension compared with wild-type mice. Two weeks of exposure of wild-type mice with cigarette smoke increased systolic blood pressure by 17 mmHg, which was similar to the effect of a subpresssor dose of angiotensin II (0.2 mg·kg−1·day−1), leading to a moderate increase to the prehypertensive level. Cigarette smoke exposure and a low dose of angiotensin II cooperatively induced severe hypertension in wild-type mice, but the scavenging of mitochondrial H2O2 in mCAT mice completely prevented the development of hypertension. Cigarette smoke and angiotensin II cooperatively induced oxidation of cardiolipin (a specific biomarker of mitochondrial oxidative stress) in wild-type mice, which was abolished in mCAT mice. Cigarette smoke and angiotensin II impaired endothelium-dependent relaxation and induced superoxide overproduction, which was diminished in mCAT mice. To mimic the tobacco smoke exposure, we used cigarette smoke condensate, which induced mitochondrial superoxide overproduction and reduced endothelial nitric oxide (a hallmark of endothelial dysfunction in hypertension). Western blot experiments indicated that tobacco smoke and angiotensin II reduce the mitochondrial deacetylase sirtuin-3 level and cause hyperacetylation of a key mitochondrial antioxidant, SOD2, which promotes mitochondrial oxidative stress.

NEW & NOTEWORTHY This work demonstrates tobacco smoking-induced mitochondrial oxidative stress, which contributes to endothelial dysfunction and development of hypertension. We suggest that the targeting of mitochondrial oxidative stress can be beneficial for treatment of pathological conditions associated with tobacco smoking, such as endothelial dysfunction, hypertension, and cardiovascular diseases.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mitochondrial-oxidative-stress-in-smoking-and-hypertension/ .
Recent Progress on Gold-Nanocluster-Based Fluorescent Probe for Environmental Analysis and Biological Sensing
Authors: Liu Mingxian , Tang Fenglin , Yang Zhengli , Xu Jing , Yang Xiupei
Published: January 2019

Gold nanoclusters (AuNCs) are one of metal nanoclusters, which play a pivotal role in the recent advances in the research of fluorescent probes for their fluorescence effect. They are favored by most researchers due to their strong stability in fluorescence and adjustability in fluorescence wavelength when compared to traditional organic fluorescent dyes. In this review, we introduce various synthesis strategies of gold-nanocluster-based fluorescent probes and summarize their application for environmental analysis and biological sensing. The use of gold-nanocluster-based fluorescent probes for the analysis of heavy metals and inorganic and organic pollutants is covered in the environmental analysis while biological labeling, imaging, and detection are presented in biological sensing.
Copigmentation with Sinapic Acid Improves the Stability of Anthocyanins in High-Pressure-Processed Strawberry Purees
Authors: Terefe Netsanet Shiferaw , Netzel Gabriele A. , Netzel Michael E.
Published: January 2019

This study investigated the impact of copigmentation with sinapic acid on the stability of anthocyanins in strawberry purees of three commercial cultivars (Camarosa, Rubygem, and Festival) after high-pressure processing (HPP; 600 MPa/5 min) and thermal processing (TP; 88°C/2 min) and during three months of refrigerated storage. Copigmentation did not have a significant effect on the stability of anthocyanins during processing with 14% to 30% degradation observed with no significant difference among cultivars or the processing technique. On the contrary, copigmentation significantly (p<0.05) improved the stability of anthocyanins in HPP samples during storage, most probably via the formation of intramolecular complexes which improve the resistance of anthocyanins to degradation. The anthocyanin contents of the copigmented HPP Camarosa, Rubygem, and Festival samples were, respectively, 42%, 40%, and 33% higher than their noncopigmented counterparts at the end of the three-month storage. Copigmentation also improved the retention of the total antioxidant capacity of the HPP-processed strawberry samples. The TPC of the copigmented HPP Camarosa, Rubygem, and Festival samples was, respectively, 66%, 65%, and 85% higher than that of the non-copigmented samples after three months of storage, whereas the respective ORAC values were 36.5%, 59.3%, and 35.3% higher. In contrast, copigmentation did not improve the stability of anthocyanins in TP samples, although significant (p<0.05) improvement in antioxidant capacity was also observed in TP samples due to the antioxidant nature of the copigment.
Enhanced Motivational Modulation of Motor Behaviour with Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease
Authors: Kojovic Maja , Higgins Andrea , Mir Pablo , Jahanshahi Marjan
Published: January 2019

Background. Motivational improvement of movement speed in Parkinson’s disease (PD) is observed in life-threatening situations and has been empirically demonstrated in experimental studies using reaction time paradigms. Objectives. To address two clinically relevant questions: first, if in PD, motivational modulation through provision of monetary incentive on a sorting task that approximates performance on everyday life tasks affects movement speed. Second, how this effect is compared between PD patients treated with medication or subthalamic deep brain stimulation. Methods. We used the Card Arranging Reward Responsivity Objective Test that shares component processes with everyday life tasks to compare reward responsivity of movement speed in 10 PD patients with STN-DBS, 10 nonoperated medicated PD patients, both OFF and ON their usual medications/stimulation, and 11 age-matched healthy controls. Results. Despite longer disease duration and more severe motor symptoms, STN-DBS PD patients with the stimulator turned ON showed greater improvement of movement speed with the prospect of monetary incentive compared to both medicated PD patients and healthy participants. Discussion. The effect of monetary incentive on movement speed in PD patients is more pronounced with STN-DBS than dopaminergic medications, suggesting that motivational modulation of movement speed may be enhanced as a direct consequence of STN stimulation.
Study of PEM Fuel Cell End Plate Design by Structural Analysis Based on Contact Pressure
Authors: Dey Tapobrata , Deshpande Jaydeep , Singdeo Debanand , Ghosh Prakash C.
Published: January 2019

A fuel cell stack is configured to power any load ranging from watts to megawatt by varying cells connected in series. During stack assembly, major emphasis must be placed on application of adequate external pressure for reducing the ohmic losses, the purpose of which is to achieve proper contact between the cell components and minimize the contact resistance. Present work aims to study the influence of geometry of the cell, bolt configuration, gasket thickness mismatch, and material properties of different components of average and distribution contact pressure. The geometries are evaluated for end plate designs with a view to understand the pressure distribution and contact resistance in each case. Among different designs, extruded hexagon is found to perform well with an average contact pressure of 0.13 MPa and contact resistance of 28 Ω-cm2. Greater gasket thickness requires higher forces to be applied before the GDL makes contact with BPP. The effect of gasket thickness mismatch is evaluated for different values to identify its appropriate value. The pressure is applied using bolts and position and number of bolts is determined for homogeneous contact pressure on the active area. This study provides a framework for future end plate design of fuel cells.
Prepatellar Bursal Infection Caused by Mycobacterium tuberculosis with an In Situ Total Knee Arthroplasty: A Case Report and Comprehensive Literature Review
Authors: Algarni Abdulrahman D.
Published: January 2019

Prepatellar bursal infection is a rare occurrence. The incidence of tuberculosis, including musculoskeletal type, is increasing. We present a case of isolated prepatellar bursal swelling associated with a discharging sinus; the condition developed in an elderly patient 4 years after total knee arthroplasty. Aspiration of the bursa revealed acid-fast bacilli on Ziehl–Neelsen staining, typical of Mycobacterium tuberculosis; this was confirmed later on culture. The patient was successfully treated with a 6-month course of antituberculous chemotherapy. To the best of our knowledge, only two previous cases of tuberculous prepatellar bursal infection have been reported in English literature. Our case illustrates the importance of considering tuberculous prepatellar bursal infection in the differential diagnosis of anterior knee swelling. All physicians treating patients with musculoskeletal disease should be aware of the possibility of this diagnosis and maintain a high index of suspicion; this is especially true in areas where tuberculosis is still endemic and in high-risk patients, such as the elderly.
Wavelet Analysis of Daily Energy Demand and Weather Variables
Authors: Bonkaney Abdou Latif , Seidou Sanda Ibrah , Balogun Ahmed A.
Published: January 2019

In this paper, we applied the Wavelet Transform Coherence (WTC) and phase analysis to analyze the relationship between the daily electricity demand (DED) and weather variables such as temperature, relative humidity, wind speed, and radiation. The DED data presents both seasonal fluctuations and increasing trend while the weather variables depict only seasonal variation. The results obtained from the WTC and phase analysis permit us to detect the period of time when the DED significantly correlates with the weather variables. We found a strong seasonal interdependence between the air temperature and DED for a periodicity of 256-512 days and 128-256 days. The relationship between the humidity and DED also shows a significant interdependence for a periodicity of 256-512 days with average coherence equal to 0.8. Regarding the radiation and wind speed, the correlation is low with average coherence less than 0.5. These results provide an insight into the properties of the impacts of weather variables on electricity demand on the basis of which power planners can rely to improve their forecasting and planning of electricity demand.
Coprecipitation Preparation of Cu/Zn/Al-Hydrotalcite-Like Compound for Copper Removal from Electroplating Wastewater
Authors: Bai Dekui , Wang Xiaofang , Huo Dongxia , Ying Quanhong , Wang Ni , Xia Baixue
Published: January 2019

Cu/Zn/Al-hydrotalcite-like compound (Cu/Zn/Al-HTlc) was prepared by the coprecipitation method with ZnII, AlIII cations solution, and electroplating wastewater containing CuII cation. The preparation conditions of Cu/Zn/Al-HTlc were optimized. The metal ion pollutants removal effect and iodide maximum adsorption capacity of Cu/Zn/Al-HTlc were also studied. The physicochemical properties of the Cu/Zn/Al-HTlc were analyzed by X-ray diffraction, FTIR, SEM, N2 adsorption-desorption isotherms, and TG-DTG. The results showed that Cu/Zn/Al-HTlc should be prepared with the ZnII-AlIII molar ratio of 1.5 : 1, pH = 11, and aged at room temperature for 0.5 d. Structural analysis showed that the Cu/Zn/Al-HTlc was a layered compound. CuII and other metal ion pollutants can also be successfully removed from electroplating wastewater in the preparation process of Cu/Zn/Al-HTlc and reached Chinese National Emission Standard (GB 21900-2008). The optimal adsorption condition of calcinated Cu/Zn/Al-HTlc for iodide was as follows: the solid-liquid ratio was 1 : 250, the pH value was 8, and the adsorption process was carried out at 25°C for 30 min. The saturated adsorption capacity reached 1000 mg·g−1 at the optimal adsorption condition. The main reason for this high-saturated adsorption capacity of Cu/Zn/Al-HTlc was that iodide penetrated into the layered structure of Cu/Zn/Al-HTlc by physical adsorption and CuII undergoes a specific redox reaction, producing CuI. Hence, coprecipitation synthetic technology and prepared Cu/Zn/Al-HTlc could be potentially used for electroplating wastewater treatment.
Esophageal Stricture Caused by Actinomyces in a Patient with No Apparent Predisposing Factors
Authors: Zhang Allison N. , Guss Debra , Mohanty Smruti R.
Published: January 2019

Actinomyces species are Gram positive anaerobic or microaerophilic bacteria that are part of the human flora in the oropharyngeal, gastrointestinal, and genitourinary tract. In the presence of a mucosal injury, they can become pathogenic and infect the underlying tissue without respect for tissue planes, leading to abscesses, fistulas, and sinus tracts. Through contiguous and hematogenous spread, virtually any organ can become infected. The presentation can be myriad and often mimics tumors, tuberculosis, or other more common infections and inflammatory conditions. While the cervicofacial region is the most common site of infection, involvement of the esophagus is unusual. Esophageal actinomycosis mostly occurs in patients with compromised immunity or prior esophageal injuries. Occurrence in immunocompetent individuals without risk factors is exceedingly rare. We report a case of esophageal actinomycosis complicated by an esophageal stricture in a patient with no apparent predisposing conditions.
Chemical Constituents from the Roots of Polygala arillata and Their Anti-Inflammatory Activities
Authors: Xiang Wei , Zhang Guo-Dong , Li Fang-Yi , Wang Teng-long , Suo Tong-Chuan , Wang Chun-Hua , Li Zheng , Zhu Yan
Published: January 2019

A new compound, named arillatanoside E, which was elucidated as 3-O-β-D-glucopyranosyl presenegenin 28-O-β-D-xylopyranosyl-(1 ⟶ 3)-β-D-xylopyranosyl-(1 ⟶ 4)-α-L-rhamnopyranosyl-(1 ⟶ 2)-(4-O-acetyl)-β-D-fucopyranosyl ester, along with 11 known compounds was isolated from the ethanolic extract of the roots of Polygala arillata. The 11 known compounds were identified as oleanolic acid (2), 3′-E-3,4,5-trimethoxy cinnamoyl-6-benzoyl sucrose (3), trans-ferulic acid (4), trans-feruloyl-glucoside (5), feruloyl-glucoside (6), 2,4,6-trimethoxy-1-O-β-D-glycoside (7), 3-methoxy-4-hydroxybenzoic acid (8), monopentadecanoin (9), sinapic acid (10), p-hydroxybenzaldehyde (11), and palmitic acid (12). Among them, seven isolated compounds 1, 2, 4, 5, 7, 8, and 10 exhibited little cytotoxic activity on macrophage RAW 264.7 cells. Then, the inhibitory effects of 7 isolates on nitric oxide (NO) production in lipopolysaccharide-activated macrophages were evaluated. As a result, 3 compounds have significant anti-inflammatory activity, and they were arillatanoside E (1), oleanolic acid (2), and 2,4,6-trimethoxy-1-O-β-D-glycoside (7).
Biofortification of Spring Barley Grain with Microelements through Sulfur Fertilization
Authors: Barczak Bożena , Jastrzębska Magdalena , Kostrzewska Marta K.
Published: January 2019

One means of enriching plants with microelements is agronomic biofortification, whereby the mineral composition of plants is stimulated through appropriate fertilization. A fertilizer component which has received much attention in recent years is sulphur. Due to the significant reduction in SO2 emissions from industrial sources to the atmosphere, a progressive deficiency of this nutrient has been observed in soils in Poland and other parts of the world. Therefore, a study was undertaken to assess the effect of different application rates (20 and 40 kg·ha−1) and forms (elemental and ionic) of sulphur on the content of selected micronutrients (Mn, Fe, Zn, and Cu) and their proportions (Fe : Mn) in the grain of the Antek variety of spring barley. In a three-year single-factor field experiment setup on luvisols with low content of sulphur, the following fertilizers were tested: ammonium sulphate, potassium sulphate, and Wigor S (80% elemental sulphur and 20% bentonite). It was demonstrated that, in the fertilization of spring barley, supplementation of NPK with sulphur can be regarded as an agronobmic method of biofortification of grain with micronutrients because it beneficially affects the content of manganese, iron, zinc, and copper in the grain. An increase in the content of these micronutrients was found in the grain of plants fertilized with sulphur in comparison to plants that were not fertilized with this nutrient in each of the growing seasons. Ammonium sulphate, compared to the other fertilizers tested, had the greatest impact on the content and uptake of all micronutrients, with the exception of zinc. Marked differences in the effect of the application rates of 20 and 40 kg·S·ha−1 were observed only for fertilizers containing the ionic form of sulphur. The beneficial effect of sulphur on the biofortification of microelements in spring barley grain indicates the need to include this nutrient in cultivation of this species.
Identification of the Potential Metabolic Pathways Involved in the Hepatic Tumorigenesis of Rat Diethylnitrosamine-Induced Hepatocellular Carcinoma via 1H NMR-Based Metabolomic Analysis
Authors: Chen Minjiang , Lu Siming , Zheng Hong , Xu Min , Song Jingjing , Yang Weibin , Weng Qiaoyou , Zheng Liyun , Fan Xiaoxi , Cheng Xingyao , Gao Hongchang , Ji Jiansong
Published: January 2019

The systemic investigation of the metabolic pathways associated with the hepatic tumorigenesis is important to discover novel biomarkers and identify the potential pathogenesis. Here, the 1H nuclear magnetic resonance- (1H NMR-) based metabolomic analysis was used to monitor the whole process of rat diethylnitrosamine-induced HCC. Intraperitoneal administration of diethylnitrosamine (DEN) was used to induce primary HCCs in male Sprague-Dawley rats. Magnetic resonance imaging (MRI) examinations were performed to follow the tumor formation and growth in the liver and H&E staining was used to confirm MR imaging findings. The rats with DEN treatment and control rats without DEN were euthanized at the time points of 3, 8, and 15 weeks after the start of modeling. 1H NMR-based metabolomic analysis was used to explore hepatic metabolite changes and certify key metabolic pathways in the process of tumor tumorigenesis. Our MRI results depicted the formation of HCC nodules in ten rats 14 weeks after DEN injection which were confirmed by histology. Twenty-four different metabolites were identified and quantified by 1H NMR spectroscopy; OPLS-DA models and corresponding VIP plots analysis further identified ten metabolites associated with the abnormal metabolism. The aberrant glucose, lipid, and glutathione-glutamine-glutamate metabolism could be detected involving in the process of hepatic tumorigenesis, which provides an important evidence for the in-depth study of subsequent molecular mechanisms, especially the glutathione-glutamine-glutamate metabolism.
Modelos psicopatológicos integrativos para la formulación diagnóstica en psiquiatría de niños y adolescentes
Authors: Pacheco Pacheco Bernardo Enrique
Published: January 2019

La psiquiatría de niños y adolescentes si quiere tener una línea de acción clínica más efectiva necesita de paradigmas o modelos de comprensión de los fenómenos psicopatológicos. La elección de un modelo o de una perspectiva de análisis ante un determinado caso en muchas ocasiones es un desafío. Aunque el psiquiatra haya sido formado en una teoría o un modelo determinado, la práctica psiquiátrica muchas veces lo insta a buscar modelos más pluralistas e integrativos que den cuenta de un modo más global de la realidad que vive el niño o adolescente psíquicamente afectado.El propósito de este artículo es realizar una reflexión teórica - clínica de distintos modelos de comprensión psicopatológica que pueden ser útiles de considerar cuando se procede a realizar una formulación diagnóstica en psiquiatría infanto juvenil. Se revisan los modelos psicopatológicos tradicionales básicos y se describen algunos modelos complementarios que pueden servir de apoyo a la evaluación psiquiátrica.Se espera que el artículo sea un aporte fundamentalmente para los nuevos profesionales que se están formando en la especialidad y que necesitan de orientaciones clínicas para la realización de un diagnóstico psiquiátrico.
IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells
Authors: Alaeddine Mohamad , Prat Mélissa , Poinsot Véréna , Gouazé-Andersson Valérie , Authier Hélène , Meunier Etienne , Lefèvre Lise , Alric Camille , Dardenne Christophe , Bernad José , Alric Laurent , Segui Bruno , Balard Patricia , Couderc François , Couderc Bettina , Pipy Bernard , Coste Agnès
Published: January 2019

Macrophage-mediated cytotoxicity is controlled by surface receptor expression and activation. Despite the numerous studies documenting the role of macrophage C-type lectin receptors (CLR) in pathogen elimination, little is known about their contribution to antitumor responses. Here, we report that IL13 inhibits T-cell lymphoma and ovarian adenocarcinoma development in tumor-bearing mice through the conversion of tumor-supporting macrophages to cytotoxic effectors, characterized by a CLR signature composed of dectin-1 and mannose receptor (MR). We show that dectin-1 and MR are critical for the recognition of tumor cells through sialic acid–specific glycan structure on their surface and for the subsequent activation of macrophage tumoricidal response. Finally, we validated that IL13 antitumor effect mediated by dectin-1 and MR overexpression on macrophages can extend to various types of human tumors. Therefore, these results identify these CLRs as potential targets to promote macrophage antitumor response and represent an attractive approach to elicit tumor-associated macrophage tumoricidal properties.
Influence of Storage and Preservation Techniques on Egg-Derived Carotenoids: A Substantial Source for Cutaneous Antioxidants
Authors: Painsi Clemens , Hesterberg Karoline , Lademann Jürgen , Knorr Dietrich , Patzelt Alexa , Vandersee Staffan , Meinke Martina C. , Richter Heike , Bob Adrienne , Knorr Fanny , Quehenberger Franz , Lange-Asschenfeldt Bernhard
Published: January 2019

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.
Nomograms of Fetal Cardiac Dimensions at 18–41 Weeks of Gestation
Authors: García-Otero Laura , Gómez Olga , Rodriguez-López Mérida , Torres Ximena , Soveral Iris , Sepúlveda-Martínez Álvaro , Guirado Laura , Valenzuela-Alcaraz Brenda , López Marta , Martínez Josep Maria , Gratacós Eduard , Crispi Fàtima
Published: January 2019

Objective: There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a well-defined echocardiographic methodology in a low-risk population. Methods: This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation. Results: Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively). Conclusions: We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling.
Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study
Authors: Nunthapiwat Sujinun , Sekararithi Ratanaporn , Wanapirak Chanane , Sirichotiyakul Supatra , Tongprasert Fuanglada , Srisupundit Kasemsri , Luewan Suchaya , Tongsong Theera
Published: January 2019

Objective: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. Methods: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. Results: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. Conclusion: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.
Cholesterol Crystals in Embolic Debris are Associated with Postoperative Cerebral Embolism after Carotid Artery Stenting
Authors: Maekawa Kota , Shibata Masunari , Nakajima Hideki , Kitano Yotaro , Seguchi Masaru , Kobayashi Kazuto , Sano Takanori , Yabana Tadashi , Miya Fumitaka
Published: January 2019

Object: We investigated possible associations among the presence of cholesterol crystals in embolic debris, the proportions of debris components, and postoperative cerebral embolism in patients undergoing carotid artery stenting (CAS). Methods: Sixty-seven consecutive procedures were performed for internal carotid artery stenosis with CAS at our hospital between November 2015 and February 2018. Procedures for emergency CAS for stroke in evolution or crescendo transient ischemic attack were excluded (n = 12). The embolic debris from remaining procedures (n = 55) was stained with hematoxylin-eosin and the red blood cells, white blood cells, and fibrin were quantified by color-based segmentation. Cholesterol crystals and calcification were examined histopathologically. Diffusion-weighted imaging (DWI) was performed 1–3 days after CAS, and the images were used to classify procedures according to the presence of new lesions. Results: Of the 55 CAS procedures, new DWI lesions were identified after 32. One patient had symptomatic cerebral embolism. Higher proportions of patients with cholesterol crystals in embolic debris (17 vs. 78%, p < 0.001) and higher proportion of white blood cells (mean 2.3 [0–9.9] vs. 4.2% [0–29.9%], p < 0.01) were observed in the embolic debris of procedures with and without new DWI lesions. Conclusions: Cholesterol crystals were common in the embolic debris from patients with postoperative ischemic lesions after CAS. These results suggest that inflammatory destabilization of the intraplaque lipid component is related to postprocedural DWI lesions.
A Case of Streptozocin Monotherapy for Unresectable Duodenal Neuroendocrine Tumor G2
Authors: Miyagawa Koji , Nakabayashi Yudai , Ishihara Yosuke , Todo Momoko , Fuji Nobuaki
Published: January 2019

Background: Duodenal neuroendocrine tumors (NET) are rare, and few reports have demonstrated the effectiveness of chemotherapy for duodenal NET, with not many other treatment options available. Here, we present a case of unresectable duodenal NET G2 that was effectively treated with streptozocin (STZ) monotherapy. We also perform a literature review. Case Summary: A 57-year-old man presented with multiple lymph node metastasis, liver metastasis, and bone metastasis that occurred after the primary resection of the duodenal NET G2. His long-term survival was obtained; the duration of stable disease exceeded 1 year and 6 months following STZ monotherapy. In addition, his CA 19–9 levels, which previously were increasing, normalized following treatment. Conclusion: To our knowledge, no study has reported the effectiveness of STZ monotherapy for duodenal NET. Our findings demonstrate that for unresectable duodenal NETs, STZ should be first administered as a high volume/single dose to stabilize the disease. However, if the disease progresses, a combination therapy may be effective in obtaining a long-term prognosis of the patient. Furthermore, CA19–9 levels may be an effective factor for determining the therapeutic effect of STZ in NET with other metastases.
Beyond KRAS: Practical Molecular Targets in Pancreatic Adenocarcinoma
Authors: Grinshpun Albert , Zarbiv Yonaton , Roszik Jason , Subbiah Vivek , Hubert Ayala
Published: January 2019

Pancreatic adenocarcinoma (PDAC) has a grim prognosis. Molecular and genomic analyses revealed that the striking majority of these tumors are driven by KRAS mutation, currently not amenable to targeted therapy. However, other driver mutations were found in a small fraction of patients. Herein we report of 3 cases of patients with metastatic PDAC and wildtype KRAS, found to harbor BRAF or RET pathogenic alterations. The patients were treated with targeted therapies with variable success. In our opinion, those proof-of-concept cases argue in favor of additional research and clinical trials’ effort in this small but significant PDAC population with uncommon driver mutations.
C4d in Native Glomerular Diseases
Authors: Chandra Preeti
Published: January 2019

Complement activation occurs in many glomerular diseases, the exact pathway(s) of activation has been studied in detail in some diseases but not in all. C4d is generated by the activation of classical and lectin pathways, and its presence can point to the activation of either of these pathways. This review aims to summarize the available data with regard to the deposition of glomerular C4d in native kidney biopsies in different glomerular pathologies that may be useful for future research into the role of complement activation in glomerular diseases. While there is more information on C4d in certain diseases (e.g., Immunoglobulin A (IgA) nephropathy), there is scant data in other diseases (such as focal segmental glomerulosclerosis).
Luís Bernardo Honwana, imobilidade e violência sob o olhar infantil
Authors: Borges Marana
Published: January 2019

O livro de contos Nós matamos o Cão Tinhoso!, de Luís Bernardo Honwana, publicado em 1964, foi um marco na literatura contemporânea de Moçambique. Nesta resenha, analiso a segunda edição brasileira da obra, que inclui mais um conto. Proponho uma leitura dos contos que leve em consideração o olhar infantil sobre a violência e o consequente desconcerto causado no leitor. A impossibilidade de dar sentido à violência impede os personagens de se rebelarem contra o arbítrio colonial.
Pseudoblock of the Posterior Mitral Line With Epicardial Bridging Connections Is a Frequent Cause of Complex Perimitral Tachycardias
Authors: Barkagan Michael , Shapira-Daniels Ayelet , Leshem Eran , Shen Changyu , Anter Elad
Published: January 2019

Background:

The mitral isthmus is the critical element of perimitral reentrant tachycardias. Prolongation in transisthmus conduction time and differential pacing techniques are commonly used to determine block. However, these may not distinguish block from slow conduction or conduction via epicardial bridging connections. The aim of this study was to examine these standard criteria for mitral line block with endocardial and epicardial activation mapping.

Methods:

In 56 patients, posterior mitral line was performed using radiofrequency ablation. Conduction block was defined as transisthmus time (≥100 ms) and reversal of coronary sinus activation during pacing from the left atrial appendage. These results were compared with high-resolution activation mapping (Rhythmia) of the endocardium and epicardium via the coronary sinus.

Results:

Mitral block determined by pacing was achieved in 51 out of 56 (91%) patients. In 11 out of 51 (21.6%), activation mapping demonstrated residual endocardial (3/11; 27.2%) or epicardial (8/11; 72.7%) connections. Epicardial bridging connections were distant from the line (2.4±1.6 cm), inserting laterally at the proximal-middle coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium (7/11; 63.6%). Mitral line block was achieved in 75% by targeting these insertion site(s). The transisthmus conduction time had limited predictive value for distinguishing block from pseudoblock.

Conclusions:

Standard criteria for posterior mitral line block may not distinguish block from pseudoblock. In particular, epicardial bridging connections can result in prolonged transisthmus conduction time and reversal in coronary sinus activation to falsely suggest block. These connections are a frequent cause for complex circuits, and their insertion site(s) can be targeted for ablation.
Strength of Evidence Underlying the American Heart Association/American College of Cardiology Guidelines on Endovascular and Surgical Treatment of Peripheral Vascular Disease:
Authors: Sardar Partha , Giri Jay , Jaff Michael R. , Parikh Sahil A. , Kundu Amartya , White Christopher J. , Chatterjee Saurav , Kennedy Kevin F. , Desai Nihar R. , Hyder Omar N. , Mukherjee Debabrata , Shishehbor Mehdi H. , Abbott J. Dawn , Aronow Herbert D.
Published: January 2019

Background:

The objective of this study was to evaluate the evidence-base supporting the American Heart Association and American College of Cardiology guidelines on peripheral vascular interventions.

Methods and Results:

American Heart Association/American College of Cardiology guideline documents available as of May 2018 were abstracted for both endovascular and surgical peripheral vascular intervention. The number of recommendations, class of recommendations (I, II, and III) and the distribution of their respective level of evidence (LOE; A, B, and C) were determined for each procedure. Guidelines were also evaluated for changes in recommendations over time. Of 5 current guidelines reporting 134 recommendations, only 13% were supported by LOE A and 39% were supported by LOE C. Overall, most recommendations were class II (54%), while 35% were class I. Lower LOEs were observed for interventions for pulmonary embolism/deep vein thrombosis (A 0%, B 24%, C 76%), inferior vena cava filter (A 0%, B 31%, C 69%), and renal artery stenosis (A 0%, B 67%, C 33%). Comparatively higher LOE A was observed for endovascular stroke therapy (24%). Compared with previous versions, total number of recommendations for lower extremity peripheral artery disease in the current guideline, decreased from 49 to 26, without an improvement in high-quality evidence.

Conclusions:

There is significant variation in the LOE supporting various peripheral vascular intervention in the current American Heart Association/American College of Cardiology guidelines. Overall, the availability of high-quality evidence remains low and the LOE appears insufficient to support many guideline recommendations for peripheral vascular intervention. These findings highlight the need for more objective and comparative evidence to support the use of endovascular and surgical therapy and in some areas, for updated guidelines.