bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study
Authors: Berzigotti Annalisa , Albillos Agustín , Villanueva Candid , Genescá Joan , Ardevol Alba , Augustín Salvador , Calleja Jose Luis , Bañares Rafael , García‐Pagán Juan Carlos , Mesonero Francisco , Bosch Jaime ,   on behalf of the Ciberehd SportDiet Collaborative Group
Published: December 2016

Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16‐week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health‐related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, –5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (–23.7 ± 19.9% vs. –8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End‐Stage Liver Disease scores did not change. Conclusion: Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293‐1305).
Deciding what is possible and impossible following hippocampal damage in humans
Authors: McCormick Cornelia , Rosenthal Clive R. , Miller Thomas D. , Maguire Eleanor A.
Published: December 2016

There is currently much debate about whether the precise role of the hippocampus in scene processing is predominantly constructive, perceptual, or mnemonic. Here, we developed a novel experimental paradigm designed to control for general perceptual and mnemonic demands, thus enabling us to specifically vary the requirement for constructive processing. We tested the ability of patients with selective bilateral hippocampal damage and matched control participants to detect either semantic (e.g., an elephant with butterflies for ears) or constructive (e.g., an endless staircase) violations in realistic images of scenes. Thus, scenes could be semantically or constructively ‘possible’ or ‘impossible’. Importantly, general perceptual and memory requirements were similar for both types of scene. We found that the patients performed comparably to control participants when deciding whether scenes were semantically possible or impossible, but were selectively impaired at judging if scenes were constructively possible or impossible. Post‐task debriefing indicated that control participants constructed flexible mental representations of the scenes in order to make constructive judgements, whereas the patients were more constrained and typically focused on specific fragments of the scenes, with little indication of having constructed internal scene models. These results suggest that one contribution the hippocampus makes to scene processing is to construct internal representations of spatially coherent scenes, which may be vital for modelling the world during both perception and memory recall. © 2016 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Acute moderate exercise improves mnemonic discrimination in young adults
Authors: Suwabe Kazuya , Hyodo Kazuki , Byun Kyeongho , Ochi Genta , Yassa Michael A. , Soya Hideaki
Published: December 2016

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long‐term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise‐enhanced DG activation in rats, and acute moderate exercise‐enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10‐min moderate exercise (50%
O2peak) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG‐mediated pattern separation in humans, proposing a useful human acute‐exercise model for analyzing the neuronal substrate underlying acute and regular exercise‐enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc.
Nanofluid Flow in a Porous Channel with Suction and Chemical Reaction using Tiwari and Das's Nanofluid Model
Authors: Chen Hui , Xiao Tianli , Shen Ming
Published: December 2016

In this paper, an analysis is made for a nanofluid flow in a porous channel by introducing the conservation equation of nanoparticle volume fraction into Tiwari and Das's nanofluid model. The suction and chemical reaction are also considered in this work. The governing partial differential equations are simplified by employing a new variable and transformed into a system of high‐order nonlinear ordinary differential equations by similarity transformations. The Keller box method is used to solve this problem numerically. In addition, the influences of significant physical parameters on the distributions of the velocity and temperature as well as nanoparticle concentration are graphically presented and discussed in detail. It is found that there exists a critical value of the permeable parameter which determines the influence law of nanoparticle volume fraction parameter on skin friction coefficient and local Sherwood number. The results also indicate that the concentration increases sharply with the Schmidt number and chemical reaction parameter.
Chromatin remodelling and DNA repair genes are frequently mutated in endometrioid endometrial carcinoma
Authors: García‐Sanz Pablo , Triviño Juan Carlos , Mota Alba , Pérez López María , Colás Eva , Rojo‐Sebastián Alejandro , García Ángel , Gatius Sonia , Ruiz María , Prat Jaime , López‐López Rafael , Abal Miguel , Gil‐Moreno Antonio , Reventós Jaume , Matias‐Guiu Xavier , Moreno‐Bueno Gema
Published: December 2016

In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non‐endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome. We focused on low‐grade, non‐ultramutated tumours as these tumours have a worse prognosis than the ultramutated POLE‐positive endometrioid endometrial carcinomas (EECs). We performed exome‐sequencing of 11 EECs with matched normal tissue and subsequently validated 15 candidate genes in 76 samples. For the first time, we show that mutations in chromatin remodelling‐related genes (KMT2D, KMT2C, SETD1B and BCOR) and in DNA‐repair‐related genes (BRCA1, BRCA2, RAD50 and CHD4) are frequent in this subtype of endometrial cancer. The alterations to these genes occurred with frequencies ranging from 35.5% for KMT2D to 10.5% for BRCA1 and BCOR, with some showing a tendency toward co‐occurrence (RAD50‐KMT2D and RAD50‐SETD1B). All these genes harboured specific mutational hotspots. In addition, the mutational status of KMT2C, KMT2D and SETD1B helps to predict the degree of myometrial invasion, a critical prognostic feature. These results highlight the possible implication of these genes in this disease, creating opportunities for new therapeutic approaches.
Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration
Authors: Agerbæk Mette Ø. , Pereira Marina A. , Clausen Thomas M. , Pehrson Caroline , Oo Htoo Zarni , Spliid Charlotte , Rich Jamie R. , Fung Vincent , Nkrumah Francis , Neequaye Janet , Biggar Robert J. , Reynolds Steven J. , Tosato Giovanna , Pullarkat Sheeja T. , Ayers Leona W. , Theander Thor G. , Daugaard Mads , Bhatia Kishor , Nielsen Morten A. , Mbulaiteye Sam M. , Salanti Ali
Published: December 2016

Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria‐infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non‐malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor site for VAR2CSA‐expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA‐specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non‐malignant tissue encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL‐derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL‐derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.
Modulation of the anti‐inflammatory effects of phosphatidylserine‐containing liposomes by PEGylation
Authors: Quan Hongxuan , Park Hee Chul , Kim Yongjoon , Yang Hyeong‐Cheol
Published: December 2016

Inhibiting liposome uptake by macrophages using polyethylene glycol (PEG) surface modifications is a widely used approach for extending the half‐life of liposomes circulating in the blood. However, the biological effects of PEGylated liposomes on macrophages have not yet been thoroughly investigated. The purpose of this study was to examine the effects of PEGylated phosphatidylserine‐containing liposomes (PEG‐PSLs) on the expression of two inflammation‐associated cytokines, tumor necrosis factor‐α (TNF‐α) and transforming growth factor‐β (TGF‐β), in the murine macrophage‐like cell line RAW 264.7. Previous studies have demonstrated that PSLs inhibit TNF‐α secretion and enhance TGF‐β synthesis in macrophages by mimicking apoptotic cells. We found that PEGylation differentially affected the TNF‐α and TGF‐β levels. The PSL‐mediated inhibitory effect on TNF‐α secretion was enhanced by PEGylation, and PEG‐PSLs decreased TGF‐β levels compared with non‐PEGylated PSLs. Fluorescence‐activated cell sorting analysis demonstrated that 1% PEGylation disturbed the incorporation of PSLs into macrophages. The interference of uptake is thought to extend the binding interaction between PS to PS receptors for PSL‐mediated inhibition of TNF‐α expression. Together, these findings indicate that PEG‐PSLs can prevent TNF‐α secretion without increasing TGF‐β levels in macrophages, and they support the potential clinical use of PEG‐PSLs as anti‐inflammatory agents with a relatively low potential to induce tissue fibrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1479–1486, 2017.
Super‐resolution structure of DNA significantly differs in buccal cells of controls and Alzheimer's patients
Authors: Garcia Angeles , Huang David , Righolt Amanda , Righolt Christiaan , Kalaw Maria Carmela , Mathur Shubha , McAvoy Elizabeth , Anderson James , Luedke Angela , Itorralba Justine , Mai Sabine
Published: December 2016

The advent of super‐resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super‐resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age‐ and gender‐matched healthy, non‐caregiver controls. In this super‐resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D‐SIM). Quantitation of the super‐resolution DNA structure revealed that the nuclear super‐resolution DNA structure of individuals with AD significantly differs from that of their controls (p < 0.05) with an overall increase in the measured DNA‐free/poor spaces. This represents a significant increase in the interchromatin compartment. We also find that the DNA structure of AD significantly differs in mild, moderate, and severe disease with respect to the DNA‐containing and DNA‐free/poor spaces. We conclude that whole genome remodeling is a feature of buccal cells in AD.
Variability in zonal location of winter East Asian jet stream
Authors: Wu Sha , Sun Jianqi
Published: December 2016

This study reveals that the winter East Asian jet stream (EAJS) shows a strong variability in its zonal location; this topic has received less attention compared with the EAJS intensity and meridional location variability in previous studies. We show that the mid‐to‐high latitude climate system is mainly responsible for the EAJS eastward shift and the tropical system is closely related with the EAJS westward shift. In the EAJS east‐located years, North Pacific Oscillation undergoes a positive phase, which can enhance the eastern part of the EAJS over the North Pacific, favouring the eastward shift of the EAJS. In the west‐located years, the tropical convection over the Indian Ocean is strong, which can strengthen the zonal angular momentum transport from the Tropics to subtropical westerly belt. Consequently, the western part of the EAJS enhances and the EAJS shifts westward. In addition, the east‐located EAJS is related to the intensified Aleutian Low and East Asian trough, and thus, Northeast China, Korean Peninsula, and Japan experience low temperatures. On the other hand, the west‐located EAJS is associated with the weakened mid‐Asian ridge and cold‐temperature advection over southern East Asia, and thus, regions from mid‐Asia southeastward to southern China experience cold temperatures. Therefore, the zonal location of the EAJS is a potentially good index of the northern or southern East Asian anomalous temperature pattern.
On the impact of gaps on trend detection in extreme streamflow time series
Authors: Slater Louise , Villarini Gabriele
Published: December 2016

Streamflow time series often contain gaps of varying length and location. However, the influence of these gaps on trend detection is poorly understood and cannot be estimated a priori in trend detection studies. We simulated the effects of varying gap size (1, 2, 5, and 10 years) and location (one quarter, one third, and half of the way) on the detection rate of significant monotonic trends in annual maxima and peaks‐over‐threshold, based on the most commonly‐used trend tests in time series of varying length (from 15 to 150 years) and trend magnitude (β1). Results show that, in comparison with the complete time series, the loss in trend detection rate tends to grow with (1) increasing gap size, (2) increasing gap distance from the middle of the time series, (3) decreasing β1 slope, and (4) decreasing time series length. Based on these findings, we provide objective recommendations and cautionary remarks for maximal gap allowance in trend detection in extreme streamflow time series.
Corn silage replacement with barley silage in dairy cows' diet does not change milk quality, cheese quality and yield
Authors: Migliorati Luciano , Boselli Leonardo , Pirlo Giacomo , Moschini Maurizio , Masoero Francesco
Published: December 2016

BACKGROUND

Considering that water availability for agricultural needs is being restricted, an alternative to corn in animal nutrition should be explored in the Po Valley. The present study aimed to evaluate the effects of either a partial (Trial I) or a total (Trial II) corn silage substitution with barley silage in dairy cows' diet on milk yield and composition, its coagulation properties, cheese yield and the sensorial profile of 16‐month‐aged Grana Padano cheese.

RESULTS

A partial or a total substitution of corn silage with barley silage had no effect on milk yield. Milk fat content in Trial I and milk urea content in both trials were higher with barley silage based diets than in corn silage based diets. No effects were observed concerning the lactodinamographic profile for milk aptitude to cheese‐making, cheese yield and its organoleptic traits between feed treatments in Trials I and II. In both trials, hardness, friability and solubility scores were generally lower than reference values, whereas deformability, elasticity and stickiness scores were generally higher than reference values.

CONCLUSION

A partial or a total substitution of corn silage with barley silage in diets for dairy cows did not induce any negative effects on animal performance, nor on milk‐quality traits, cheese quality and yield. © 2016 Society of Chemical Industry
Frequency‐tuned contactless conductivity detector for the electrophoretic separation of clinical samples in capillaries with very small internal dimensions
Authors: Tůma Petr
Published: December 2016

An axial design of a capacitively coupled contactless conductivity detector was tested in combination with fused‐silica capillaries with internal diameters of 10, 15, and 25 μm, which are used for high‐efficiency electrophoretic separation. The transmission of the signal in the detection probe dependent on the specific conductivity of the solution in the capillary in the range 0–278 mS.m−1 has a complex character and a minimum appears on the curve at very low conductivities. The position of the minimum of the calibration dependence gradually shifts with decreasing frequency of the exciting signal from 1.0 to 0.25 MHz toward lower specific conductivity values. The presence of a minimum on the calibration curves is a natural property of the axial design of contactless conductivity detector, demonstrated by solution of the equivalent electrical circuit of the detection probe, and is specifically caused by the use of shielding foil. The behavior of contactless conductivity detector in the vicinity of the minimum was documented for practical separations of amino acids in solutions of 3.2 M acetic acid with addition of 0–50% v/v methanol.
Preliminary study of a novel transfection modality for in vivo siRNA delivery to vocal fold fibroblasts
Authors: Kraja Iv , Bing Renjie , Hiwatashi Nao , Rousseau Bernard , Nalband Danielle , Kirshenbaum Kent , Branski Ryan C.
Published: December 2016

Objective

An obstacle to clinical use of RNA‐based gene suppression is instability and inefficiency of current delivery modalities. Nanoparticle delivery likely holds great promise, but the kinetics and transfection conditions must be optimized prior to in vivo utility. We investigated a RNA nanoparticle complex incorporating a lipitoid transfection reagent in comparison to a commercially available reagent.

Study Design

In vitro.

Methods

We investigated which variables influence transfection efficiency of lipitoid oligomers and a commercially available reagent across species, in vitro. These variables included duration, dose, and number of administrations, as well as serum and media conditions. The target gene was Smad3, a signaling protein in the transforming growth factor‐β cascade implicated in fibroplasia in the vocal folds and other tissues.

Results

The two reagents suppressed Smad3 mRNA for up to 96 hours; lipitoid performed favorably and comparably. Both compounds yielded 60% to 80% mRNA knockdown in rat, rabbit, and human vocal fold fibroblasts (P < 0.05 relative to control). Dose and number of administrations played a significant role in gene suppression (P < 0.05). Suppression was more dose‐sensitive with lipitoid. At a constant siRNA concentration, a 50% decrease in gene expression was observed in response to a five‐fold increase in lipitoid concentration. Increased number of administrations enhanced gene suppression, ∼45% decrease between one and four administrations. Neither serum nor media type altered efficiency.

Conclusion

Lipitoid effectively knocked down Smad3 expression across multiple transfection conditions. These preliminary data are encouraging, and lipitoid warrants further investigation with the goal of clinical utility.

Level of Evidence

NA. Laryngoscope, 127:E231–E237, 2017
Results May Vary: Overcoming Variability in Consumer Response to Advertising Music
Authors: Craton Lincoln G. , Lantos Geoffrey P. , Leventhal Richard C.
Published: December 2016

Although listening to music seems effortless, it actually involves many separate psychological mechanisms. This article describes and extends the multimechanism framework proposed by Juslin and colleagues, highlighting how the operation of psychological mechanisms leads to two general types of variability in consumer response to advertising music. First, the risk ofbetween‐consumer variability(individual differences) in musical response is moderate or high for most mechanisms, and it often depends on each individual's particular history of exposure to music (listening biography). Second,within‐consumer variabilityoccurs when different mechanisms have contrasting effects, so that an individual consumer's musical response is often mixed (e.g., guilty pleasures, bittersweet feelings, pleasurable sadness). Both types of variability can negatively impact advertising objectives (message reception, recall, acceptance, brand attitudes, etc.). The article offers preliminary suggestions for how marketers can use a multimechanism approach to successfully incorporate music in commercials and reduce the risk of unanticipated consumer responses. It ends with proposals for further research.
Neoalbaconol inhibits angiogenesis and tumor growth by suppressing EGFR‐mediated VEGF production
Authors: Yu Xinfang , Li Wei , Deng Qipan , You Shuo , Liu Haidan , Peng Songling , Liu Xiaolan , Lu Jingchen , Luo Xiangjian , Yang Lifang , Tang Min , Weng Xinxian , Yi Wei , Liu Wenbin , Wu Shengqi , Ding Zhihui , Feng Tao , Zhou Jian , Fan Jia , Bode Ann M. , Dong Zigang , Liu Jikai , Cao Ya
Published: December 2016

Neoalbaconol, derived from Albatrellus confluens, shows anti‐cancer activities in the previously study, but its role in angiogenesis is unknown. Here, we determined whether neoalbaconol could attenuate angiogenesis and how does it occur. Data demonstrated that neoalbaconol could inhibit the proliferation of breast cancer cells and induce apoptosis. Also, neoalbaconol suppressed vascular endothelial growth factor (VEGF)‐induced human umbilical vascular endothelial cells (HUVECs) proliferation, migration, invasion, and capillary‐like tube formation in vitro and reduced tumor angiogenesis in vivo. VEGF receptor activation and the downstream signal transduction cascades activation were inhibited by neoalbaconol. Additionally, neoalbaconol blocked EGFR‐mediated VEGF production. EGFR overexpression reversed the neoalbaconol‐induced VEGF reduction, confirming the importance of the EGFR inhibition in anti‐angiogenesis of neoalbaconol. Furthermore, neoalbaconol inhibited tumor growth and tumor angiogenesis in a breast cancer xenograft model in vivo. Taken together, these results indicate that neoalbaconol could inhibit tumor angiogenesis and growth through direct suppression effects on vascular endothelial cells and reduction of proangiogenic factors in cancer cells.
Persistent phosphorylation at specific H3 serine residues involved in chemical carcinogen‐induced cell transformation
Authors: Zhu Xiaonian , Li Daochuan , Zhang Zhengbao , Zhu Wei , Li Wenxue , Zhao Jian , Xing Xiumei , He Zhini , Wang Shan , Wang Fangping , Ma Lu , Bai Qing , Zeng Xiaowen , Li Jie , Gao Chen , Xiao Yongmei , Wang Qing , Chen Liping , Chen Wen
Published: December 2016

Identification of aberrant histone H3 phosphorylation during chemical carcinogenesis will lead to a better understanding of the substantial roles of histone modifications in cancer development. To explore whether aberrant H3 phosphorylation contributes to chemical carcinogenesis, we examined the dynamic changes of H3 phosphorylation at various residues in chemical carcinogen‐induced transformed human cells and human cancers. We found that histone H3 phosphorylation at Ser10 (p‐H3S10) and Ser28 (p‐H3S28) was upregulated by 1.5‐4.8 folds and 2.1‐4.3 folds, respectively in aflatoxin B1‐transformed hepatocytes L02 cells (L02RT‐AFB1), benzo(a)pyrene‐transformed HBE cells (HBERT‐BaP), and coke oven emissions‐transformed HBE cells (HBERT‐COE). The ectopic expression of histone H3 mutant (H3S10A or H3S28A) in L02 cells led to the suppression of an anchorage‐independent cell growth as well as tumor formation in immunodeficient mice. In addition, an enhanced p‐H3S10 was found in 70.6% (24/34) of hepatocellular carcinoma (HCC), and 70.0% (21/30) of primary lung cancer, respectively. Notably, we found that expression of H3 carrying a mutant H3S10A or H3S28A conferred to cells the ability to maintain a denser chromatin and resistance to induction of DNA damage and carcinogen‐induced cell transformation. Particularly, we showed that introduction of a mutant H3S10A abolished the bindings of p‐H3S10 to the promoter of DNA repair genes, PARP1 and MLH1 upon AFB1 treatment. Furthermore, we revealed that PP2A was responsible for dephosphorylation of p‐H3S10. Taken together, these results reveal a key role of persistent H3S10 or H3S28 phosphorylation in chemical carcinogenesis through regulating gene transcription of DNA damage response (DDR) genes.
Molecular spectrum and differential diagnosis in patients referred with sporadic or autosomal recessive osteogenesis imperfecta
Authors: Caparros‐Martin Jose A. , Aglan Mona S. , Temtamy Samia , Otaify Ghada A. , Valencia Maria , Nevado Julián , Vallespin Elena , Del Pozo Angela , Prior de Castro Carmen , Calatrava‐Ferreras Lucia , Gutierrez Pilar , Bueno Ana M. , Sagastizabal Belen , Guillen‐Navarro Encarna , Ballesta‐Martinez Maria , Gonzalez Vanesa , Basaran Sarenur Y. , Buyukoglan Ruksan , Sarikepe Bilge , Espinoza‐Valdez Cecilia , Cammarata‐Scalisi Francisco , Martinez‐Glez Victor , Heath Karen E. , Lapunzina Pablo , Ruiz‐Perez Victor L.
Published: December 2016

Background

Osteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases. Twenty patients had nonrelated parents and were sporadic, and 21 were born to consanguineous relationships.

Methods

Mutation analysis was performed using a next‐generation sequencing gene panel, homozygosity mapping, and whole exome sequencing (WES).

Results

Patients offspring of nonconsanguineous parents were mostly identified with COL1A1 or COL1A2 heterozygous changes, although there were also a few cases with IFITM5 and WNT1 heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes including CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, TMEM38B, and WNT1. In addition, two patients born to consanguineous parents were found to have de novo COL1A1 heterozygous mutations demonstrating that causative variants in the collagen I structural genes cannot be overlooked in affected children from consanguineous couples. Further to this, WES analysis in probands lacking mutations in OI genes revealed deleterious variants in SCN9A, NTRK1, and SLC2A2, which are associated with congenital indifference to pain (CIP) and Fanconi–Bickel syndrome (FBS).

Conclusion

This work provides useful information for clinical and genetic diagnosis of OI patients with no positive family history of this disease. Our data also indicate that CIP and FBS are conditions to be considered in the differential diagnosis of OI and suggest a positive role of SCN9A and NTRK1 in bone development.
Application of phage peptide display technology for the study of food allergen epitopes
Authors: Chen Xueni , Dreskin Stephen C.
Published: December 2016

Phage peptide display technology has been used to identify IgE‐binding mimotopes (mimics of natural epitopes) that mimic conformational epitopes. This approach is effective in the characterization of those epitopes that are important for eliciting IgE‐mediated allergic responses by food allergens and those that are responsible for cross‐reactivity among allergenic food proteins. Application of this technology will increase our understanding of the mechanisms whereby food allergens elicit allergic reactions, will facilitate the discovery of diagnostic reagents and may lead to mimotope‐based immunotherapy.
Lambert–Eaton myasthenic syndrome: Epidemiology and therapeutic response in the national veterans affairs population
Authors: Abenroth Daniel C. , Smith A. Gordon , Greenlee John E. , Austin Sharon D. , Clardy Stacey L.
Published: December 2016

Introduction

One nationwide study (The Netherlands) of Lambert–Eaton myasthenic syndrome (LEMS) has been published. We report LEMS epidemiology and its therapeutic response in the United States Veterans Affairs (VA) population.

Methods

Medical records for all active patients (12.5 million) in the VA health system were queried for relevant ICD‐9 codes for the period October 1, 1999 to September 30, 2013. Clinical, electrophysiologic, and serologic features were evaluated to confirm diagnosis; epidemiologic and treatment data were collected.

Results

Point prevalence was estimated at 2.6 per 1,000,000 (confirmed cases) and 3.3 per 1,000,000 (combined confirmed and probable cases). Crude prevalence was similarly estimated at 9.2 and 10.9 per 1,000,000 respectively. A total of 18 of 48 (38%) patients received 3,4‐diaminopyridine (3,4‐DAP); 14 of 18 (78%) improved.

Conclusions

This investigation was a large North American epidemiologic study of LEMS. LEMS prevalence in the national VA population was found to be similar to previously published rates in other large international populations. Most patients experienced improvement with therapy, including a majority with 3,4‐DAP. Muscle Nerve 56: 421–426, 2017
Tetraparetic critically ill patients show electrophysiological signs of myopathy
Authors: Crone Clarissa
Published: December 2016

Introduction

Critically ill patients often develop tetraparesis. It has been debated whether this is caused by neuropathy, myopathy, or both. The aim was to determine the incidence of myopathy and neuropathy in weak patients in the intensive care unit by performing several electrophysiological examinations, including quantitative electromyography (qEMG).

Methods

Forty‐nine patients referred for electrophysiological examination because of suspected critical illness‐related weakness underwent qEMG, nerve conduction studies, and direct muscle stimulation.

Results

The qEMG showed signs of myopathy in 33 of 35 patients. Direct muscle stimulation was consistent with myopathy in 31 of 34 patients. Amplitudes of compound muscle action potentials were decreased in all patients. Four patients also had signs of sensory neuropathy, which could not be explained by preexisting medical conditions.

Conclusions

When combined, the results are compatible with muscle dysfunction in all patients. This will help to direct future studies of the pathophysiology of this serious condition. Muscle Nerve 56: 433–440, 2017
Polynomial chaos‐based extended Padé expansion in structural dynamics
Authors: Jacquelin E. , Dessombz O. , Sinou J.‐J. , Adhikari S. , Friswell M. I.
Published: December 2016

The response of a random dynamical system is totally characterized by its probability density function (pdf). However, determining a pdf by a direct approach requires a high numerical cost; similarly, surrogate models such as direct polynomial chaos expansions are not generally efficient, especially around the eigenfrequencies of the dynamical system. In the present study, a new approach based on Padé approximants to obtain moments and pdf of the dynamic response in the frequency domain is proposed. A key difference between the direct polynomial chaos representation and the Padé representation is that the Padé approach has polynomials in both numerator and denominator. For frequency response functions, the denominator plays a vital role as it contains the information related to resonance frequencies, which are uncertain. A Galerkin approach in conjunction with polynomial chaos is proposed for the Padé approximation. Another physics‐based approach, utilizing polynomial chaos expansions of the random eigenmodes, is proposed and compared with the proposed Padé approach. It is shown that both methods give accurate results even if a very low degree of the polynomial expansion is used. The methods are demonstrated for two degree‐of‐freedom system with one and two uncertain parameters. Copyright © 2016 John Wiley & Sons, Ltd.
Development of a Predictive Model for Drug‐Related Problems in Kidney Transplant Recipients
Authors: Covert Kelly L. , Mardis Caitlin R. , Fleming James N. , Pilch Nicole A. , Meadows Holly B. , Mardis Benjamin A. , Mohan Prince , Posadas‐Salas Maria , Srinivas Titte , Taber David J.
Published: December 2016

Study Objective

Drug‐related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists’ workflow in a chronic kidney transplant clinic.

Design

Prospective observational study.

Setting

Chronic kidney transplant clinic at a large, tertiary care, academic hospital.

Patients

Two hundred thirty‐seven adults seen in the kidney transplant clinic between September 16, 2015, and November 30, 2015, who were at least 90 days posttransplantation at the time of their clinic visit.

Measurements and Main Results

Prospective data detailing DRPs and a survey assessing baseline characteristics and patient‐related outcomes were used to generate a predictive model to identify patients at risk of having six or more DRPs; the cutoff of six DRPs provided a threshold for identifying a subset of high‐risk patients on whom the transplant pharmacists could focus their efforts. DRPs were categorized as nonadherence, overdosing or underdosing, duplication of therapy, preventable adverse drug reaction, missing medication, erroneous medication, conflicting provider information, undermonitoring or lack of monitoring, and wrong medication received. In total, 865 unique DRPs were identified, and the most common were erroneous medication, missing medication, and nonadherence, accounting for 38%, 21%, and 16% of the DRPs, respectively. A nine‐variable model with a sensitivity of 62.5% and specificity of 66.7% (area under the receiver operating characteristic curve of 0.720) was developed to identify patients at risk of having six or more DRPs. The model included the following variables: age, Medicaid for prescription insurance, current employment status, medication affordability, difficulty or lack of difficulty obtaining medications from the pharmacy, negative impact of medications on quality of life, medication nonadherence, poor rating of current health status, and moderate or poor medication understanding.

Conclusion

These results demonstrated that a straightforward, 5‐minute survey completed by renal transplant recipients prior to their clinic visit may be capable of effectively determining those at risk of having six or more DRPs, potentially allowing use as a screening tool for transplant pharmacists’ workflow prioritization. External validation is needed before this tool can be used in the outpatient setting.
Stability of maleic anhydride plasma polymer film to water drop evaporation
Authors: Brioude Michel M. , Laborie Marie‐Pierre , Airoudj Aissam , Haidara Hamidou , Roucoules Vincent
Published: December 2016

Previous work revealed the possibility of controlling the nanostructuration of maleic anhydride plasma polymer (MAPP) by adjusting the plasma process parameters or adding cellulose nanocrystals (CNCs) previously on the substrate. This work aimed to evaluate the stability of MAPP coating to water drop evaporation. The evaporation process was followed by optical microscopy and the effects of substrate surface chemistry and presence of CNCs were investigated. The presence of CNCs affected not only the MAPP adhesion under wet condition, leading to an impressive morphological reconstruction of MAPP coating, but also the evaporation kinetics. Therefore, this work exhibits a simple way to obtain functional surface patterns by changing the coating wet adhesion and opens new opportunities for the utilization of CNCs.
Synthesis of Magnesium Nanofibers by Electroless Reduction and their Hydrogen Interaction Properties
Authors: Sun Yahui , Aguey‐Zinsou Kondo‐Francois
Published: December 2016

Magnesium (Mg) is successfully synthesized from the direct reduction of dibutylmagnesium (MgBu2) with calcium (Ca). By adding 1‐dodecanethiol, the morphology of the magnesium particles is controlled and magnesium nanofibers with a length of 0.4–4 µm and a width of 40 nm are obtained. Besides magnesium nanofibers, isolated irregular shaped calcium particles are also observed as a by‐product of the reaction. The nanofibers readily absorbed hydrogen at 300 °C and hydrogen release occurred at much lower temperatures (360 °C) compared to the equivalent bulk material. More remarkably, these nanofibers remain stable during hydrogen cycling, but they partially react with the remaining calcium to form the ternary hydride phase Ca19Mg8H54—a phase that is usually obtained at high temperatures >500 °C and hydrogen pressure 2500 MPa. Hydrogen absorption within these magnesium nanofibers shows a slightly lower enthalpy as compared to bulk magnesium. However, the hydrogen desorption properties are influenced by the presence of calcium and its reaction with magnesium.
Effect of acrylodan conjugation and forced oxidation on the structural integrity, conformational stability, and binding activity of a glucose binding protein SM4 used in a prototype continuous glucose monitor
Authors: Hickey John M. , Sahni Neha , Chaudhuri Rajoshi , D'Souza Ajit , Metters Andrew , Joshi Sangeeta B. , Russell Middaugh C. , Volkin David B.
Published: December 2016

Continuous glucose monitoring (CGM) devices offer diabetes patients a convenient approach to assist in controlling blood glucose levels. A prototype CGM has been developed that uses the emission profile of a polarity‐sensitive fluorophore (acrylodan) conjugated to a glucose/galactose‐binding protein (SM4‐AC) to measure the concentration of glucose in vivo. During development, a decrease in the devices signal intensity was observed in vivo over time, which was postulated to be result of oxidative degradation of SM4‐AC. A comprehensive physicochemical analysis of SM4‐AC was pursued to identify potential mechanisms of signal intensity loss in this CGM during in vitro forced oxidation studies. An assessment of the structural integrity and conformational stability of SM4‐AC indicated a relatively decreased polarity and lower tertiary structure stability compared to unconjugated protein (SM4). The stability and polarity of SM4‐AC was also altered in the presence of H2O2. Furthermore, a time‐dependent loss in the fluorescence signal of SM4‐AC was observed when incubated with H2O2. An LC‐MS peptide mapping analysis of these protein samples indicated that primarily two Met residues in SM4‐AC were susceptible to oxidation. When these two residues were genetically altered to an amino acid not prone to oxidation, the glucose binding ability of the protein was retained and no loss of acrylodan fluorescence was observed in the presence of H2O2. Genetic alteration of these two residues is proposed as an effective approach to increase the long‐term stability of SM4‐AC within this prototype CGM in vivo.
Ultrasound image based visual servoing for moving target ablation by high intensity focused ultrasound
Authors: Seo Joonho , Koizumi Norihiro , Mitsuishi Mamoru , Sugita Naohiko
Published: December 2016

Background

Although high intensity focused ultrasound (HIFU) is a promising technology for tumor treatment, a moving abdominal target is still a challenge in current HIFU systems. In particular, respiratory‐induced organ motion can reduce the treatment efficiency and negatively influence the treatment result. In this research, we present: (1) a methodology for integration of ultrasound (US) image based visual servoing in a HIFU system; and (2) the experimental results obtained using the developed system.

Materials and methods

In the visual servoing system, target motion is monitored by biplane US imaging and tracked in real time (40 Hz) by registration with a preoperative 3D model. The distance between the target and the current HIFU focal position is calculated in every US frame and a three‐axis robot physically compensates for differences. Because simultaneous HIFU irradiation disturbs US target imaging, a sophisticated interlacing strategy was constructed.

Results

In the experiments, respiratory‐induced organ motion was simulated in a water tank with a linear actuator and kidney‐shaped phantom model. Motion compensation with HIFU irradiation was applied to the moving phantom model. Based on the experimental results, visual servoing exhibited a motion compensation accuracy of 1.7 mm (RMS) on average. Moreover, the integrated system could make a spherical HIFU‐ablated lesion in the desired position of the respiratory‐moving phantom model.

Conclusions

We have demonstrated the feasibility of our US image based visual servoing technique in a HIFU system for moving target treatment.
NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer
Authors: Duan Shun , Yang Yajuan , Zhang Cunli , Zhao Nana , Xu Fu‐Jian
Published: December 2016

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.
Behaviour of over‐reinforced high‐strength concrete beams confined with post‐tensioned steel straps – an experimental investigation
Authors: Ma Chau‐Khun , Awang Abdullah Zawawi , Garcia Reyes , Omar Wahid , Pilakoutas Kypros
Published: December 2016

This study examines the flexural behaviour of high‐strength concrete (HSC) beams confined using an innovative steel strapping tensioning technique (SSTT) able to provide active confinement. Twelve over‐reinforced HSC beams (fc = 50 or 80 MPa) were designed to fail prematurely by concrete crushing at mid‐span. The mid‐span region of eight such beams was confined externally using the SSTT with different steel strap confinement ratios, the aim of which was to delay concrete crushing. The test results are discussed in terms of the failure modes, load‐deflection response and the concrete and tensile reinforcement strains observed. Although the unconfined beams failed in a brittle manner with no post‐peak deflection, the steel straps were very effective at enhancing the post‐peak deformation of the SSTT‐confined beams by up to 126 %. Moreover, for the beams tested in this study, the use of the SSTT led to failures after yielding of the tensile reinforcement. The proposed SSTT can be used to confine HSC elements where ductility is required.
Photoactivatable Substrates: A Material‐Based Approach for Dissecting Cell Migration
Authors: Nakanishi Jun
Published: December 2016

Photoactivatable substrates, which show changes in surface cell adhesiveness in response to photoirradiation, are promising platforms for cell manipulation with high spatiotemporal resolution. In addition to having applications in cell and tissue engineering, these materials are unique tools for basic biological sciences research, and they complement conventional genetic engineering technologies. One of the most useful applications is in the study of cell migration, which occurs in various physiological and pathological processes. In this personal account, I provide a brief overview of the development of photoactivatable substrates and their applications, highlighting in particular the contributions of our research group to collective cell migration studies. This material‐based approach is useful for dissecting the molecular biological and mechanobiological aspects of the regulatory mechanisms in the cellular social activities.