bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells
Authors: Jiang Miao , Österlund Pamela , Westenius Veera , Guo Deyin , Poranen Minna M. , Bamford Dennis H. , Julkunen Ilkka
Published: November 2018

In spite of the enormous amount of research, influenza virus is still one of the major challenges for medical virology due to its capacity to generate new variants, which potentially lead to severe epidemics and pandemics. We demonstrated here that a swarm of small interfering RNA (siRNA) molecules, including more than 100 different antiviral RNA molecules targeting the most conserved regions of the influenza A virus genome, could efficiently inhibit the replication of all tested avian and seasonal influenza A variants in human primary monocyte-derived macrophages and dendritic cells. The wide antiviral spectrum makes the virus-specific siRNA swarm a potentially efficient treatment modality against both avian and seasonal influenza viruses.
Social gradient of birthweight in England assessed using the INTERGROWTH-21st gestational age-specific standard
Authors: Hirst Jane E , Knight Hannah Ellin , Ohuma Eric O , Dwyer Terence , Hennig Benjamin D , Papageorghiou Aris T , Cheikh Ismail Leila , Villar José , Kennedy Stephen H
Published: November 2018

Objective

To determine the socioeconomic gradient of birthweights in England with reference to the prescriptive INTERGROWTH-21st Birthweight Standard.

Design

National cross-sectional study using data from Hospital Episode Statistics.

Setting

National Health Service in England.

Participants

All singleton babies, live born between 34 weeks’ gestation and 42 weeks’ gestation, between 1 April 2011 and 31 March 2012.

Main outcome measures

Birthweight distribution of babies with a birthweight of <10th centile or >90th centile, that is, small for gestational age (SGA) or large for gestational age (LGA) using Index of Multiple Deprivation quintiles as a proxy for socioeconomic status.

Results

Of 508 230 babies born alive between 1 April 2011 and 31 March 2012, 38 838 (7.6%) were SGA and 81 026 (15.9%) were LGA. Median birthweight was 3405 g, median z-score was 0.25 (SD 1.06). Birthweight z-score demonstrated a social gradient, from 0.26 (SD 1.1) in the most deprived areas to 0.53 (1.0) in the least deprived. Women in the most deprived areas were twice as likely to have SGA babies using the INTERGROWTH-21st chart (OR 1.94; 95% CI 1.87 to 2.01) compared with those in the least deprived areas. If all women had the same rate of SGA equivalent to those living in the least deprived areas, approximately 12 410 (30%) fewer babies would be born SGA in England each year.

Conclusions

This study gives a measure of the social gradient in singleton SGA and LGA babies across England using an international standard of newborn size at birth.
Food sources of fructose-containing sugars and glycaemic control: systematic review and meta-analysis of controlled intervention studies
Authors: Choo Vivian L , Viguiliouk Effie , Blanco Mejia Sonia , Cozma Adrian I , Khan Tauseef A , Ha Vanessa , Wolever Thomas M S , Leiter Lawrence A , Vuksan Vladimir , Kendall Cyril W C , de Souza Russell J , Jenkins David J A , Sievenpiper John L
Published: November 2018

Objective

To assess the effect of different food sources of fructose-containing sugars on glycaemic control at different levels of energy control.

Design

Systematic review and meta-analysis of controlled intervention studies.

Data sources

Medine, Embase, and the Cochrane Library up to 25 April 2018.

Eligibility criteria for selecting studies

Controlled intervention studies of at least seven days’ duration and assessing the effect of different food sources of fructose-containing sugars on glycaemic control in people with and without diabetes were included. Four study designs were prespecified on the basis of energy control: substitution studies (sugars in energy matched comparisons with other macronutrients), addition studies (excess energy from sugars added to diets), subtraction studies (energy from sugars subtracted from diets), and ad libitum studies (sugars freely replaced by other macronutrients without control for energy). Outcomes were glycated haemoglobin (HbA1c), fasting blood glucose, and fasting blood glucose insulin.

Data extraction and synthesis

Four independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by random effects models and overall certainty of the evidence assessed by the GRADE approach (grading of recommendations assessment, development, and evaluation).

Results

155 study comparisons (n=5086) were included. Total fructose-containing sugars had no harmful effect on any outcome in substitution or subtraction studies, with a decrease seen in HbA1c in substitution studies (mean difference −0.22% (95% confidence interval to −0.35% to −0.08%), −25.9 mmol/mol (−27.3 to −24.4)), but a harmful effect was seen on fasting insulin in addition studies (4.68 pmol/L (1.40 to 7.96)) and ad libitum studies (7.24 pmol/L (0.47 to 14.00)). There was interaction by food source, with specific food sources showing beneficial effects (fruit and fruit juice) or harmful effects (sweetened milk and mixed sources) in substitution studies and harmful effects (sugars-sweetened beverages and fruit juice) in addition studies on at least one outcome. Most of the evidence was low quality.

Conclusions

Energy control and food source appear to mediate the effect of fructose-containing sugars on glycaemic control. Although most food sources of these sugars (especially fruit) do not have a harmful effect in energy matched substitutions with other macronutrients, several food sources of fructose-containing sugars (especially sugars-sweetened beverages) adding excess energy to diets have harmful effects. However, certainty in these estimates is low, and more high quality randomised controlled trials are needed.

Study registration

Clinicaltrials.gov (NCT02716870).
Evaluation of a staff training programme to reimplement a comprehensive health assessment
Authors: Turcotte Luke A , Tran Jake , Moralejo Joshua , Curtin-Telegdi Nancy , Eckel Leslie , Hirdes John P
Published: November 2018

Background

Health information systems with applications in patient care planning and decision support depend on high-quality data. A postacute care hospital in Ontario, Canada, conducted data quality assessment and focus group interviews to guide the development of a cross-disciplinary training programme to reimplement the Resident Assessment Instrument–Minimum Data Set (RAI-MDS) 2.0 comprehensive health assessment into the hospital’s clinical workflows.

Methods

A hospital-level data quality assessment framework based on time series comparisons against an aggregate of Ontario postacute care hospitals was used to identify areas of concern. Focus groups were used to evaluate assessment practices and the use of health information in care planning and clinical decision support. The data quality assessment and focus groups were repeated to evaluate the effectiveness of the training programme.

Results

Initial data quality assessment and focus group indicated that knowledge, practice and cultural barriers prevented both the collection and use of high-quality clinical data. Following the implementation of the training, there was an improvement in both data quality and the culture surrounding the RAI-MDS 2.0 assessment.

Conclusions

It is important for facilities to evaluate the quality of their health information to ensure that it is suitable for decision-making purposes. This study demonstrates the use of a data quality assessment framework that can be applied for quality improvement planning.
Hepatozoon canis in three imported dogs: a new tickborne disease reaching the United Kingdom
Authors: Attipa Charalampos , Maguire David , Solano‐Gallego Laia , Szladovits Balazs , Barker Emily N , Farr Alison , Baneth Gad , Tasker Séverine
Published: November 2018

An increasing number of non‐endemic vectorborne pathogens have been described in dogs imported to the UK in the past two decades. Recently, an outbreak of canine babesiosis in south‐east England has raised veterinary awareness with regard to the impact of such diseases on the UK canine population. Canine hepatozoonosis, caused by Hepatozoon canis and transmitted by the ingestion of Rhipicephalus sanguineus ticks, is widespread in the Mediterranean basin. Herein we describe the first three molecularly confirmed clinical cases of canine hepatozoonosis in dogs imported into the UK. Veterinarians in the UK should be aware of H canis as a potential infection in imported dogs, especially in the face of the expanding distribution of R sanguineus ticks in Europe.
Effects of jet-breaker dimensional characteristics on drop manhole hydraulic performance
Authors: Hasheminejad Seyedreza , Khanjani Mohammad-Javad , Barani Gholam-Abbas
Published: November 2018

Drop manholes prevent excessive flow velocity and provide energy dissipation in steep urban sewer and drainage systems. Their poor hydraulic performance under Regime R2, in which the inlet jet collides with the manhole outlet, was improved by the jet-breaker. However, this device should still be properly sized to efficiently enhance manhole operation. In this paper, effects of jet-breaker length, width, sagitta, angle, and inlet pipe filling ratio on drop manhole performance, were investigated experimentally. Two-level factorial design and dimensional analysis were both utilized to design the experiments to study drop manhole energy dissipation and air demand as responses. Statistical analysis of the results revealed both significant design factors and regression models for each response. Neither jet-breaker length nor width had significant effects. However, the responses were improved by increasing both jet-breaker angle and inlet pipe filling ratio. Jet-breaker sagitta had a different effect on each response; a flat plate was more appropriate for energy dissipation while a curved plate decreased air demand. Simultaneous analysis of regression models determined the proper levels of significant design factors as 80% filling ratio of the inlet pipe, jet-breaker angle at 70°, and its sagitta equal to 0.
Geology, lithogeochemistry, and significance of porphyry intrusions associated with gold mineralization within the Timmins–Porcupine gold camp, Canada
Authors: MacDonald Peter J. , Piercey Stephen J.
Published: November 2018

The Timmins–Porcupine gold camp, Abitibi greenstone belt, is host >60 Moz of Au with many gold deposits spatially associated with porphyry intrusions and the Porcupine–Destor deformation zone (PDDZ). Porphyry intrusions form three suites. The Timmins porphyry suite (TIS) consists of high-Al tonalite–trondjhemite–granodiorite (TTG) with calc–alkalic affinities and high La/Yb ratios and formed during ∼2690 Ma D1-related crustal thickening and hydrous partial melting of mafic crust where garnet and hornblende were stable in the residue. The Carr Township porphyry intrusive suite (CIS) and the granodiorite intrusive suite (GIS) also have high-Al TTG, calc-alkalic affinities, but were generated 10–15 million years after the TIS; the CIS were generated at shallower depths (during postorogenic extension?) with no garnet in the crustal residue, whereas the GIS formed during D2 thrust-related crustal thickening and partial melting where garnet was stable in the residue. Gold mineralization is preferentially associated with the TIS, and to a lesser extent the GIS, proximal to the PDDZ. Intrusions near mineralization have abundant sericite, carbonate, and sulphide alteration. These intrusions exhibit low Na2O and Sr, and high Al2O3/Na2O, K2O, K2O/Na2O, Rb, and Cs, (i.e., potassic alteration); sulfide- and carbonate-altered porphyries have high (CaO + MgO + Fe2O3)/Al2O3 and LOI values. Although porphyries are not genetically related to gold mineralization, they are spatially related and are interpreted to reflect the emplacement of intrusions and subsequent Au-bearing fluids along the same crustal structures. The intrusive rocks also served as structural traps, where gold mineralization precipitated in dilatant structures along the margins of intrusions during regional (D3?) deformation.
Scattering state in GUP by Milne’s differential equation
Authors: Armat A. , Nejad S. Mohammad Moosavi
Published: November 2018

In this paper, our main aim is to obtain the transmission (T) and the reflection (R) coefficients for one-dimensional scattering state of the spin-[Formula: see text] particles in an interaction with a special nuclear potential. For this reason, at first, we consider Dirac equation and then obtain the Milne’s nonlinear differential equation due to minimal length from Schrödinger-like equation and then calculate the T- and R-coefficients using one-dimensional Woods–Saxon potential on the basis of the generalized uncertainty principle. Finally, we will check the validity and the correctness of our results.
THE FIRST ATTEMPT OF THE BIOKINETIC GA-67 MODEL APPLICATION TO CANINE LIVER CARCINOMA: CASE-CONTROL STUDY VIAIN-VIVOGAMMA CAMERA/8-SLICE CT TECHNIQUE
Authors: CHUANG CHAO-HSUN , CHEN CHIH-FENG , TSENG NENG-CHUNG , CHAN KUANG-LI , PAN LUNG-FA , PAN LUNG-KWANG
Published: November 2018

The biokinetic model of Ga-67 evolution was elaborated in this study for the case-control group of canine liver carcinoma via in-vivo gamma camera/8-slice CT technique. One liver carcinoma dog and two normal dogs were anesthetized with the further whole body scanning by a gamma camera to acquire the time-dependent Ga-67 concentration variations among eight compartments, namely: 1. body fluid, 2. liver, 3. GI Tract, 4. kidney, 5. heart, 6. remainder, 7. bladder, and 8. excretion. Each compartment was assumed to have a unique biological half-life and to be connected to other ones. The initial simplification of assigned compartments was performed based on the general-purpose biokinetic model recommended by the ICRP-30 report. Each object/dog underwent eight scans within 72[Formula: see text]h. The time-dependent empirical data were normalized to the maximal counts/pixel/sec and then integrated with the theoretical estimates, in order to optimize the correlations among compartments. A self-developed program run in MATLAB was used to reflect the actual performance acquired from the gamma camera scanning, while the dimensionless agreement (AT) was applied to assess the discrepancies between empirical and theoretical results. An AT of zero implies a perfect agreement between the theoretical and empirical results, while AT under 20 indicates an excellent consistency between the optimal computational and empirical data, whereas a wide fluctuation of the obtained ATs in the range of 7%–60% corresponded to a medium range of data disagreement in this study. The liver carcinoma dog has revealed a longer biological half-life than normal dogs in the limited range (40 versus 35 or 15[Formula: see text]h). However, the quantified data for other compartments and branching ratios among compartments provided a quite robust substantiation for constructing the biokinetic model of Ga-67 being administrated in the canine hepatic survey.
MONITORING AND EVALUATION OF SPORTS LOAD FOR PRIMARY AND MIDDLE SCHOOL STUDENTS
Authors: LUO QI , YANG LIN , ZHANG SONG , SU JUN , HAO DONGMEI
Published: November 2018

In recent years, the physical fitness of primary and middle school students in China has been declining. In addition to the unbalanced nutrition, the main reason is the insufficient load of physical exercise. The aim of this study is to explore the quantitative methods of sports load of primary and middle school students by means of training impulse (TRIMP), and to evaluate the feasibility and effectiveness of this method. In the study, 297 students (168 boys, 129 girls) were divided into intervention group and control group. All of students were tested with height, weight, vital capacity, sit-and-reach, 50[Formula: see text]m running, 50[Formula: see text]m [Formula: see text] 8 round trip, one-minute sit-up, one-minute skip and other physical indicators in gym class, the change of resting heart rate, sport heart rate, exercise time were collected before and after by independent development of the heart-rate wrist belt. The mean sport heart rate, mean exercise time (the cumulative time of the heart rate between 120 and 200[Formula: see text]bpm), the time of different intensity exercise and the TRIMP were calculated. The results of correlation analysis showed that the change of TRIMP was positively correlated with the change of vital capacity and one-minute sit up, and increasing sports load could improve the physical health, verifying the feasibility of using the TRIMP to quantify the sports load. At the same time, the TRIMP was expressed in scores to make the understanding easy for the teachers and students or any audience in general.
INFRA-OBTURATOR TENSION SLING FOR URINARY INCONTINENCE TREATMENT
Authors: KIM YEONGJIN , NA YOUNGJIN , KIM SOOBYEONG , YI JEONGYOON , AHN BUMMO
Published: November 2018

Stress incontinence occurs due to the inability to control an urge to urinate, which affects the quality of daily life. Although there is an existing therapeutics with polymer mesh tape, it is hard to fix around the urethra to restore the function of the pubourethral ligament. Therefore, in this research, an infra-obturator tension (IOT) sling was introduced to minimize the mobility of the bladder and urethra against intra-abdominal pressure. To verify the IOT performance, two different hypotheses were formulated: The hardness and volume of the IOT support the urethra and help prevent it from deforming by intra-abdominal pressure. The rotatory motion of the IOT can bend the urethra at the contact point and help restore the function of pubourethral ligament to increase vaginal tension. For the first hypothesis, a finite element simulation was conducted using three-dimensional geometrical model obtained by the computed tomography images of patients. For the second hypothesis, surgeons performed an IOT insertion operation and analyzed the sling rotation from the patients’ CT images (mean: 21∘). From the results, the mobility of the urethra was decreased because of IOT insertion. The mobility was also decreased because of the subsequent fibrotic changes from the encapsulation of the IOT.
Opportunities and challenges in search interaction
Authors: White Ryen W.
Published: November 2018

Seeking to address a wider range of user requests toward task completion.
How to get things done when you don't feel like it
Authors: Matsudaira Kate
Published: November 2018

Five strategies for pushing through.
A chance gardener
Authors: Neville-Neil George V.
Published: November 2018

Harvesting open source products and planting the next crop.
Distinct roles of histamine H1- and H2-receptor signaling pathways in inflammation-associated colonic tumorigenesis
Authors: Shi Zhongcheng , Fultz Robert S. , Engevik Melinda A. , Gao Chunxu , Hall Anne , Major Angela , Mori-Akiyama Yuko , Versalovic James
Published: November 2018

Inflammatory bowel disease (IBD) is a well-known risk factor for the development of colorectal cancer. Prior studies have demonstrated that microbial histamine can ameliorate intestinal inflammation in mice. We tested the hypothesis whether microbe-derived luminal histamine suppresses inflammation-associated colon cancer in Apcmin/+ mice. Mice were colonized with the human-derived Lactobacillus reuteri. Chronic inflammation was induced by repeated cycles of low-dose dextran sulfate sodium (DSS). Mice that were given histamine-producing L. reuteri via oral gavage developed fewer colonic tumors, despite the presence of a complex mouse gut microbiome. We further demonstrated that administration of a histamine H1-receptor (H1R) antagonist suppressed tumorigenesis, while administration of histamine H2-receptor (H2R) antagonist significantly increased both tumor number and size. The bimodal functions of histamine include protumorigenic effects through H1R and antitumorigenic effects via H2R, and these results were supported by gene expression profiling studies on tumor specimens of patients with colorectal cancer. Greater ratios of gene expression of H2R ( HRH2) vs. H1R ( HRH1) were correlated with improved overall survival outcomes in patients with colorectal cancer. Additionally, activation of H2R suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibited chemokine gene expression induced by H1R activation in colorectal cancer cells. Moreover, the combination of a H1R antagonist and a H2R agonist yielded potent suppression of lipopolysaccharide-induced MAPK signaling in macrophages. Given the impact on intestinal epithelial and immune cells, simultaneous modulation of H1R and H2R signaling pathways may be a promising therapeutic target for the prevention and treatment of inflammation-associated colorectal cancer.

NEW & NOTEWORTHY Histamine-producing Lactobacillus reuteri can suppress development of inflammation-associated colon cancer in an established mouse model. The net effects of histamine may depend on the relative activity of H1R and H2R signaling pathways in the intestinal mucosa. Our findings suggest that treatment with H1R or H2R antagonists could yield opposite effects. However, by harnessing the ability to block H1R signaling while stimulating H2R signaling, novel strategies for suppression of intestinal inflammation and colorectal neoplasia could be developed.
ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function
Authors: Zhou Suhan , Jiang Shan , Guo Jie , Xu Nan , Wang Qin , Zhang Gensheng , Zhao Liang , Zhou Qin , Fu Xiaodong , Li Lingli , Patzak Andreas , Hultström Michael , Lai En Yin
Published: November 2018

Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Ser473 and eNOS at Ser1177. Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis, and improving microvascular endothelial dysfunction. rhADAMTS13 could be a promising strategy to treat AKI in clinical settings.
Intrinsic foot muscles contribute to elastic energy storage and return in the human foot
Authors: Kelly Luke A. , Farris Dominic J. , Cresswell Andrew G. , Lichtwark Glen A.
Published: November 2018

The human foot is uniquely stiff to enable forward propulsion, yet also possesses sufficient elasticity to act as an energy store, recycling mechanical energy during locomotion. Historically, this dichotomous function has been attributed to the passive contribution of the plantar aponeurosis. However, recent evidence highlights the potential for muscles to modulate the energetic function of the foot actively. Here, we test the hypothesis that the central nervous system can actively control the foot’s energetic function, via activation of the muscles within the foot’s longitudinal arch. We used a custom-built loading apparatus to deliver cyclical loads to human feet in vivo, to deform the arch in a manner similar to that observed in locomotion. We recorded foot motion and forces, alongside muscle activation and ultrasound images from flexor digitorum brevis (FDB), an intrinsic foot muscle that spans the arch. When active, the FDB muscle fascicles contracted in an isometric manner, facilitating elastic energy storage in the tendon, in addition to the energy stored within the plantar aponeurosis. We propose that the human foot is akin to an active suspension system for the human body, with mechanical and energetic properties that can be actively controlled by the central nervous system.

NEW & NOTEWORTHY The human foot is renowned for its ability to recycle mechanical energy during locomotion, contributing up to 17% of the energy required to power a stride. This mechanism has long been considered passive in nature, facilitated by the elastic ligaments within the arch of the foot. In this paper, we present the first direct evidence that the intrinsic foot muscles also contribute to elastic energy storage and return within the human foot. Isometric contraction of the flexor digitorum brevis muscle tissue facilitates tendon stretch and recoil during controlled loading of the foot. The significance of these muscles has been greatly debated by evolutionary biologists seeking to understand the origins of upright posture and gait, as well as applied and clinical scientists. The data we present here show a potential function for these muscles in contributing to the energetic function of the human foot.
Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review
Authors: Lee Jiwon M. , Shin Jaewon , Kim Sol , Gee Heon Yung , Lee Joon Suk , Cha Do Hyeon , Rim John Hoon , Park Se-Jin , Kim Ji Hong , Uçar Ahmet , Kronbichler Andreas , Lee Keum Hwa , Shin Jae Il
Published: November 2018

Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.
Passing the Baton: Substrate Channelling in Respiratory Metabolism
Authors: Fernie Alisdair R. , Zhang Youjun , Sweetlove Lee J.
Published: November 2018

Despite species-specific differences in the pathways of respiratory metabolism are remarkably conserved across the kingdoms of life with glycolysis, the tricarboxylic acid cycle, and mitochondrial electron transport chain representing the major components of the process in the vast majority of organisms. In addition to being of critical importance in fueling life itself these pathways serve as interesting case studies for substrate channelling with research on this theme having been carried out for over 40 years. Here we provide a cross-kingdom review of the ample evidence for protein-protein interaction and enzyme assemblies within the three component pathways as well as describing the scarcer available evidence for substrate channelling itself.
Protection of Kaempferol on Oxidative Stress‐Induced Retinal Pigment Epithelial Cell Damage
Authors: Du Weiwei , An Yuanlong , He Xiangdong , Zhang Donglei , He Wei
Published: November 2018

The protection of retinal pigment epithelium (RPE) injury plays an important role in the prevention of or in delaying the pathological progress of retinal degeneration diseases, like age‐related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa. Oxidative stress has been identified as a major inducer of RPE injury, which eventually could lead to a loss of vision. Kaempferol is a natural flavonoid widely distributed in many edible plants, fruits, and traditional medicines and has been reported to have antioxidant, anti‐inflammatory, anticancer, and antimicrobial activities. The present study demonstrates that the total antioxidant capacity of kaempferol is approximately two times stronger than that of lutein which is also a natural antioxidant that is widely used in the prevention or treatment of AMD. Our data indicates that kaempferol protects human RPE cells (ARPE‐19) from hydrogen peroxide‐ (H2O2‐) induced oxidative cell damage and apoptosis through the signaling pathways involving Bax/Bcl‐2 and caspase‐3 molecules proofed by real‐time PCR and Western blot results. Kaempferol also inhibits the upregulated vascular endothelial growth factor (VEGF) mRNA expression levels induced by H2O2 in ARPE‐19 cells and affects the oxidation and antioxidant imbalanced system in ARPE‐19 cells treated by H2O2 through the regulations of both the activities of reactive oxygen species (ROS) and superoxide dismutase (SOD). Furthermore, our in vivo experimental results show that in sodium iodate‐induced retinal degeneration rat model, kaempferol could protect sodium iodate‐induced pathological changes of retina tissue and retinal cells apoptosis as well as the upregulated VEGF protein expression in RPE cells. In summary, these novel findings demonstrate that kaempferol could protect oxidative stressed‐human RPE cell damage through its antioxidant activity and antiapoptosis function, suggesting that kaempferol has a potential role in the prevention and therapeutic treatment of AMD or other retinal diseases mediated by oxidative stress.
A Unique Case of Midvariant Reverse Takotsubo Cardiomyopathy
Authors: Moazez Carmel , Zeitjian Vicken , Mehdizadeh Azar
Published: November 2018

Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is known to have 4 variants: apical, midventricular, basal, and focal. Here, we report the 2nd case of reverse midvariant (midventricular) stress cardiomyopathy and the 1st case of reverse midvariant takotsubo cardiomyopathy with apical thrombus.
Two Cases of Acute Cholecystitis and Symptomatic Choledocholithiasis in Two Women Less than 40-Years-of-Age with Hormonal Intrauterine Devices
Authors: Shields Helen M. , Sidhu Hasrat
Published: November 2018

Levonorgestrel uterine implants are accepted as a safe and efficacious method of contraception. One of the two major health side effects in a large controlled study of subcutaneous hormonal implants with levonorgestrel was a significant increase in gallbladder disease. Gallbladder hypomotility is recognized as a side effect of the levonorgestrel (progesterone). We recently saw on a Gastroenterology Consult Service, two women under 40-years-of-age who had been transferred from outside hospitals with acute cholecystitis with symptomatic choledocholithiasis. Both required Endoscopic Retrograde Cholangiopancreatography and sphincterotomies in addition to laparoscopic cholecystectomies. Both had hormonal (levonorgestrel-releasing) intrauterine devices in place for contraception. Although one patient had a family history of gallstones, the other did not. Both were nonobese, young women patients. We were struck by the coincidence of seeing two such patients. Few articles in the medical literature detail the clinical risks of gallstone disease in patients with hormonal (levonorgestrel-releasing) intrauterine devices. Our experiences with these two patients led us to believe that patients with risk factors for gallstone disease, such as a positive family history, ethnic predisposition, or obesity, should be warned of possible problems, not only with gallbladder disease, but also of common duct stones.
Classification of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern in Patients with Hepatitis B Cirrhosis Using Metabonomics
Authors: Zhao Chao-qun , Chen Long , Cai Hong , Yao Wei-li , Zhou Qun , Zhu Hui-ming , Gao Yue , Liu Ping , Gou Xiao-jun , Zhang Hua
Published: November 2018

Objective. This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques. Methods. The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography–time‐of‐flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results. After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns. Conclusions. The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.
Acute Liver Injury Associated with Khat Use in a 24-Year-Old Male
Authors: Waters Mara , Oxner Adam , Krajden Sigmund , Sultanian Richard
Published: November 2018

Chewing khat leaves (Catha edulis) is common cultural practice in Eastern African countries. Khat has been implicated in cases of acute liver injury, sometimes leading to liver failure and requiring transplantation. We report the case of a 24-year-old gentleman presenting with symptoms of acute liver failure. Bloodwork demonstrated hepatocyte-predominant liver injury. Microbiological and serological hepatitis panels were negative, and his liver biopsy demonstrated acute cholestatic hepatitis. He admitted to regular khat use for several years prior to his presentation. His liver function tests improved with cessation of khat use. This is the first reported case of acute khat-associated hepatitis in Canada. Considering cultural practices such as khat chewing in presentations of acute liver injury are important when caring for diverse patient populations.
SDN Programming for Heterogeneous Switches with Flow Table Pipelining
Authors: Wang Junchang , Cheng Shaojin , Fu Xiong
Published: November 2018

High-level programming is one of the critical building blocks of the effective use of software-defined networking (SDN). Existing solutions, however, either (1) cannot utilize the state-of-the-art switches with flow table pipelining, a key technique to prevent flow rule set explosion or (2) force programmers to manually organize and manage hardware flow table pipelines, which is time-consuming and error-prone. This paper presents a high-level SDN programming framework to address these issues. The framework can automatically (1) generate rule sets for heterogeneous switches with different flow table pipelining designs and (2) update installed rules when the network state changes. As a result, the framework can not only generate efficient rule sets for switches but also provide programmers a centralized, intuitive, and hence easy-to-use programming API. Experiments show that the framework can generate compact rule sets that are 29–116 times smaller than those generated by other open-source SDN controllers. Besides, the framework is 5 times faster to recover from network link failures in comparison to other controllers.
Maximum Swing Flexion or Gait Symmetry: A Comparative Evaluation of Control Targets on Metabolic Energy Expenditure of Amputee Using Intelligent Prosthetic Knee
Authors: Cao Wujing , Zhao Weiliang , Yu Hongliu , Chen Wenming , Meng Qiaoling
Published: November 2018

Background. The metabolic energy expenditure (MEE) was the most important assessment standard of intelligent prosthetic knee (IPK). Maximum swing flexion (MSF) angle and gait symmetry (GS) were two control targets representing different developing directions for IPK. However, the few comparisons based on MEE assessment between the MSF and GS limited the development of the IPK design. Objectives. The aim of the present work was to find out the MEE difference of amputees using IPK with control targets of MSF and GS and determine which target was more suitable for the control of IPK based on the MEE assessment. Methods. The crossover trial was designed. Six unilateral transfemoral amputees participated in the study. The amputees were assessed when wearing the IPK with different control targets, namely, the maximum swing flexion angle and gait symmetry. The oxygen consumption analysis during walking at different speeds on a treadmill was carried out. Results. All subjects showed increased oxygen consumption as walking speed increased. However, no statistically significant differences were found in oxygen consumption for different control targets. The ANOVA test showed that the overall effects of the control targets of the prosthetic knee on oxygen consumption were not significant across all walking speeds. Conclusions. The control targets of MSF and GS showed no significant differences on MEE in above-knee amputees using IPK. From perspective of amputee’s metabolic costs, either maximum swing flexion or gait symmetry could be suitable control target for the IPK.
Fracture Energy Analysis of Concrete considering the Boundary Effect of Single‐Edge Notched Beams
Authors: Xu Ping , Ma Jinyi , Zhang Minxia , Ding Yahong , Meng Lingqi
Published: November 2018

The method of determining concrete fracture energy recommended by RILEM has an obvious size effect, so determining fracture energy that is unaffected by size of the test specimen is difficult. In this study, 60 high‐strength concrete single‐edge notched beams (SENBs) of different sizes, crack length‐to‐depth ratios, and span‐to‐depth ratios were subjected to the three‐point loading test as recommended by RILEM. Then, the influences of the boundary effect on the fracture energy were identified. Based on the SENB boundary effect model, a piecewise function of the interrelationships between the experimental test fracture energy Gf, the local fracture energy gf, and the fracture energy unaffected by specimen size GF was established. The applicability of the boundary effect model was verified using the test results from this study and from the previously published research. The results show that the local fracture energy distribution in the boundary influence region was nonuniform. The smaller the local fracture energy was, the closer it was to the rear boundary of the specimen. The influence length of the boundary increased with the increasing specimen size. Based on the bilinear distribution model of the local fracture energy gf, the fracture energy unaffected by beam size GF can be obtained according to the fracture energy Gf measured for laboratory‐scale small‐sized SENB specimens. Furthermore, the model predictions are in good agreement with experimental observations.
Increased Mitochondrial Protein Levels and Bioenergetics in the Musculus Rectus Femoris of Wfs1‐Deficient Mice
Authors: Eimre Margus , Paju Kalju , Peet Nadežda , Kadaja Lumme , Tarrend Marian , Kasvandik Sergo , Seppet Joosep , Ivask Marilin , Orlova Ehte , Kõks Sulev
Published: November 2018

Wfs1 deficiency leads to a progressive loss of plasma insulin concentration, which should reduce the consumption of glucose in insulin‐dependent tissues, causing a variety of changes in intracellular energy metabolism. Our objective here was to assess the changes in the amount and function of mitochondrial proteins in different muscles of Wfs1‐deficient mice. Mitochondrial functions were assayed by high‐resolution oxygraphy of permeabilized muscle fibers; the protein amount was evaluated by liquid chromatography tandem mass spectrometry (LC/MS/MS) analysis and mRNA levels of the uncoupler proteins UCP2 and UCP3 by real‐time PCR; and citrate synthase (CS) activity was determined spectrophotometrically in muscle homogenates. Compared to controls, there were no changes in proton leak and citrate synthase activity in the heart and m. soleus tissues of Wfs1‐deficient mice, but significantly higher levels of both of these factors were observed in the m. rectus femoris; mitochondrial proteins and mRNA of UCP2 were also higher in the m. rectus femoris. ADP‐stimulated state 3 respiration was lower in the m. soleus, remained unchanged in the heart, and was higher in the m. rectus femoris. The mitochondrial protein amount and activity are higher in Wfs1‐deficient mice, as are mitochondrial proton leak and oxygen consumption in m. rectus femoris. These changes in muscle metabolism may be important for identifying the mechanisms responsible for Wolfram syndrome and diabetes.
Dark Chocolate Intake Positively Modulates Redox Status and Markers of Muscular Damage in Elite Football Athletes: A Randomized Controlled Study
Authors: Cavarretta Elena , Peruzzi Mariangela , Del Vescovo Riccardo , Di Pilla Fabio , Gobbi Giuliana , Serdoz Andrea , Ferrara Roberto , Schirone Leonardo , Sciarretta Sebastiano , Nocella Cristina , De Falco Elena , Schiavon Sonia , Biondi-Zoccai Giuseppe , Frati Giacomo , Carnevale Roberto
Published: November 2018

Intensive physical exercise may cause increase oxidative stress and muscular injury in elite football athletes. The aim of this study was to exploit the effect of cocoa polyphenols on oxidative stress and muscular injuries induced by intensive physical exercise in elite football players. Oxidant/antioxidant status and markers of muscle damage were evaluated in 24 elite football players and 15 controls. Furthermore, the 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n = 12) or a control group (n = 12) for 30 days in a randomized controlled trial. Oxidative stress, antioxidant status, and muscle damage were assessed at baseline and after 30 days of chocolate intake. Compared to controls, elite football players showed lower antioxidant power and higher oxidative stress paralleled by an increase in muscle damage markers. After 30 days of dark chocolate intake, an increased antioxidant power was found in elite athletes assuming dark chocolate. Moreover, a significant reduction in muscle damage markers (CK and LDH, p < 0.001) was observed. In the control group, no changes were observed with the exception of an increase of sNox2‐dp, H2O2, and myoglobin. A simple linear regression analysis showed that sNox2‐dp was associated with a significant increase in muscle damage biomarker release (p = 0.001). An in vitro study also confirmed that polyphenol extracts significantly decreased oxidative stress in murine myoblast cell line C2C12‐derived. These results indicate that polyphenol‐rich nutrient supplementation by means of dark chocolate positively modulates redox status and reduced exercise‐induced muscular injury biomarkers in elite football athletes. This trial is registered with NCT03288623.
MobiSentry: Towards Easy and Effective Detection of Android Malware on Smartphones
Authors: Ren Bingfei , Liu Chuanchang , Cheng Bo , Guo Jie , Chen Junliang
Published: November 2018

Android platform is increasingly targeted by attackers due to its popularity and openness. Traditional defenses to malware are largely reliant on expert analysis to design the discriminative features manually, which are easy to bypass with the use of sophisticated detection avoidance techniques. Therefore, more effective and easy-to-use approaches for detection of Android malware are in demand. In this paper, we present MobiSentry, a novel lightweight defense system for malware classification and categorization on smartphones. Besides conventional static features such as permissions and API calls, MobiSentry also employs the N-gram features of operation codes (n-opcode). We present two comprehensive performance comparisons among several state-of-the-art classification algorithms with multiple evaluation metrics: (1) malware detection on 184,486 benign applications and 21,306 malware samples, and (2) malware categorization on DREBIN, the largest labeled Android malware datasets. We utilize the ensemble of these supervised classifiers to design MobiSentry, which outperforms several related approaches and gives a satisfying performance in the evaluation. Furthermore, we integrate MobiSentry with Android OS that enables smartphones with Android to extract features and to predict whether the application is benign or malicious. Experimental results on real smartphones show that users can easily and effectively protect their devices against malware through this system with a small run-time overhead.
Identifying Driver Behavior in Preturning Maneuvers Using In-Vehicle CANbus Signals
Authors: Zardosht M. , Beauchemin S. S. , Bauer M. A.
Published: November 2018

Our objective in this contribution is to categorize driver behavior in terms of preturning maneuvers. We analyze driving behavior in an urban environment prior to turns using data obtained from the CANbus of an instrumented vehicle during a one-hour driving period for 12 different individuals. CANbus data streams such as vehicle speed, gas pedal pressure, brake pedal pressure, steering wheel angle, and acceleration are collected and analyzed for 5, 10, and 15 seconds of driving prior to each turn. We consider all turns for each driver and extract statistical features from the signals and use cluster analysis to categorize drivers into groups reflecting different driving styles. The results show that using this approach we can effectively cluster drivers into two groups. The results show consistency in the membership within a cluster throughout the different timeframes. We conclude that driver behavior classification from such data streams is possible and we hope in the near future to devise driver descriptors that include additional maneuvers.