bluuebunny/crossref_metadata_2025 huggingface dataset:
The IgM pentamer is an asymmetric pentagon with an open groove that binds the AIM protein
Authors: Hiramoto Emiri , Tsutsumi Akihisa , Suzuki Risa , Matsuoka Shigeru , Arai Satoko , Kikkawa Masahide , Miyazaki Toru
Published: October 2018

We demonstrate the bona fide 2D structure of the IgM pentamer and its association with AIM protein.
GDP-
l
-fucose synthase is a CD4
+
T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis
Authors: Planas Raquel , Santos Radleigh , Tomas-Ojer Paula , Cruciani Carolina , Lutterotti Andreas , Faigle Wolfgang , Schaeren-Wiemers Nicole , Espejo Carmen , Eixarch Herena , Pinilla Clemencia , Martin Roland , Sospedra Mireia
Published: October 2018

GDP-
l
-fucose synthase is an autoantigen recognized by cerebrospinal fluid–infiltrating CD4
+
T cells from HLA-DRB3* patients with multiple sclerosis.
Predicting pathology provides prostate prognostication
Authors: Nance Elizabeth A.
Published: October 2018

A live primary cell phenotypic assay with single-cell resolution can predict postsurgical adverse pathology with >80% accuracy for patients with prostate or breast cancer.
Daptomycin Pore Formation and Stoichiometry Depend on Membrane Potential of Target Membrane
Authors: Seydlová Gabriela , Sokol Albert , Lišková Petra , Konopásek Ivo , Fišer Radovan
Published: October 2018

Daptomycin is a calcium-dependent lipodepsipeptide antibiotic clinically used to treat serious infections caused by Gram-positive pathogens. Its precise mode of action is somewhat controversial; the biggest issue is daptomycin pore formation, which we directly investigated here.
Whole-Genome Sequence of Toxic Freshwater Cyanobacterium Chrysosporum ovalisporum Strain UAM-MAO
Authors: Sanz-Alférez Soledad , Rodríguez-Sanz Carolina E. , Barón-Sola Ángel , del Campo Francisca F.
Published: October 2018

Here, we report the complete nucleotide sequence of
Chrysosporum ovalisporum
UAM-MAO, a filamentous, cylindrospermopsin-producing cyanobacterium involved in bloom forming in freshwater systems worldwide. It was isolated from an artificial pond in Madrid, Spain.
Whole-Genome Sequence of Lactobacillus salivarius DJ-sa-01, Isolated from Chicken Small Intestine
Authors: Kim Dongjun , Cho Mun-Ju , Cho Seungchan , Lee Yongjun , Byun Sung June , Lee Sukchan
Published: October 2018

We have identified the whole-genome sequence of
Lactobacillus salivarius
DJ-sa-01, a potential probiotic strain for poultry, isolated from a chicken small intestine. We used the PacBio and Illumina platforms to obtain the sequence of the entire single circular chromosome.
Maternal attitude towards delaying puberty in girls with and without a disability: a questionnaire-based study from the United Arab Emirates
Authors: Deeb Asma , Akle Mariette , Al Zaabi Abrar , Siwji Zohra , Attia Salima , Al Suwaidi Hana , Al Qahtani Nabras , Ehtisham Sarah
Published: October 2018

Background

Parental anxiety about the impact of puberty/menses, particularly in girls with severe disability leads to seeking therapeutic pubertal suppression. We aim to explore maternal attitudes and reasons for seeking pubertal suppression.

Methods

Mothers of girls receiving gonadotropin -releasing hormone analogue therapy in Mafraq hospital, Abu Dhabi were enrolled in the study. A semistructured interview was conducted to ascertain possible reasons for delaying puberty. The study group was divided into girls with a disability with central precocious puberty (CPP) or normal puberty and girls without a disability presenting with CPP.

Results

42 mother–daughter pairs were enrolled and divided into two groups; group A: 15 girls with CPP with no disability; group B: 27 girls with disability (10 had CPP (group B1) and 17 had normal pubertal timing (group B2)). Mothers in group A aimed to delay puberty, while in group B, 13 (48%) mothers desired to halt puberty and 7 (26%) requested permanent surgical intervention. Fear of short stature (15, 100%), inability to cope psychologically (10, 67%) and fear of peer rejection (9, 60%) were the main concerns in group A. In group B, mothers were concerned about menstrual hygiene management (25, 92.5%), fear of child abuse or unwanted pregnancy (15, 55%) and fear of inability to express pain/discomfort with menstruation (8, 30%).

Conclusion

Mothers of girls with a disability commonly seek medical help to delay/halt puberty due to concerns about menstrual hygiene. Short final height was the main concern for girls without a disability. Culture and religion play an important role in puberty management in girls with a disability.
How to do it: investigate exertional rhabdomyolysis (or not)
Authors: Fernandes Peter M , Davenport Richard J
Published: October 2018

Rhabdomyolysis is the combination of symptoms (myalgia, weakness and muscle swelling) and a substantial rise in serum creatine kinase (CK) >50 000 IU/L; there are many causes, but here we specifically address exertional rhabdomyolysis. The consequences of this condition can be severe, including acute kidney injury and requirement for higher level care with organ support. Most patients have ‘physiological’ exertional rhabdomyolysis with no underlying disease; they do not need investigation and should be advised to return to normal activities in a graded fashion. Rarely, exertional rhabdomyolysis may be the initial presentation of underlying muscle disease, and we review how to identify this much smaller group of patients, who do require investigation.
On the homogenization and up-scaling of a discrete element method model
Authors: Yetisir Mike , Dusseault Maurice , Gracie Robert
Published: October 2018

A Distinct Element Method (DEM) up-scaling framework is presented that estimates the parameters of a continuum constitutive model that best captures the salient features of naturally fractured rock (NFR) behaviour. Up-scaling is achieved using homogenized DEM stress–strain curves and a particle swarm optimization algorithm followed by a Levenberg–Marquardt algorithm. The effectiveness of the framework is demonstrated by up-scaling a DEM model of a NFR to a Drucker–Prager damage-plasticity model. The up-scaled continuum model is shown to compare well (<5% error) with direct numerical simulation in a slope stability analysis and requires two orders of magnitude less computational effort.
Hemipenes eversion behavior: a new form of communication in two Liolaemus lizards (Iguania: Liolaemidae)
Authors: Ruiz-Monachesi M.R. , Paz A. , Quipildor M.
Published: October 2018

Males of several animals have intromittent organs and may use these in a communicative context during sexual or intrasexual interactions. In some lizards, hemipenes eversion behavior have been observed, and the aim of this study is to find out whether this behavior is functionally significant under a communicative approach. Here, we investigated the eversion of hemipenes in the Light Blue Lizard (Liolaemus coeruleus Cei and Ortiz-Zapata, 1983) and in the Valley Lizard (Liolaemus quilmes Etheridge, 1993) by filming the response of male focal lizards in different experimental settings: (i) an agonistic context, i.e., with a conspecific male, (ii) a sexual context, i.e., with a conspecific female, and (iii) a control treatment, i.e., without a treatment lizard. In both species, focal lizards showed this behavior only in an agonistic context, with interspecific differences as follows. Liolaemus coeruleus has longer times until eversion and dragging of hemipenes; however, it has shorter time of eversion and exposition of the hemipenes. Liolaemus quilmes has the opposite pattern compared with L. coeruleus. These indicate that eversion of the hemipenes can act as a visual display and as a signal of aggressive behavior towards conspecific rival males. The present study offers a new behavioral perspective on the use of masculine genitalia in lizards.
Overview of electronic tongue sensing in environmental aqueous matrices: potential for monitoring emerging organic contaminants
Authors: Magro Cátia , Mateus Eduardo P. , Raposo Maria , Ribeiro Alexandra B.
Published: October 2018

Emerging organic contaminants (EOC) are synthetic or naturally occurring chemicals that have the potential to enter the environment and cause known or suspected adverse ecological and human health effects. Despite not being commonly monitored, EOC are often detected in effluents and water bodies because of their inefficient removal in conventional wastewater treatment plants. There is a growing concern about the presence and impact of EOC as well as the need for reliable and effective water monitoring using sensors capable of detecting the target molecules in complex media. Due to their specificities, such as fast response times, low cost, portability and user-friendly operation, electronic tongue (e-tongue) systems present some advantages over the traditional analytical techniques (e.g., chromatographic systems) used for environmental monitoring. We reviewed e-tongue sensors, focusing on their ability for real-time environmental monitoring. A bibliometric evaluation was carried out, along with a study of the status of the existing e-tongue systems, how they worked, and their applications in different fields. The potential of e-tongue sensors to detect organic contaminants in aqueous environmental matrices is discussed, with a particular focus on EOC.
Difference Hierarchies for nT τ-functions
Authors: Addabbo Darlayne , Bergvelt Maarten
Published: October 2018

We introduce hierarchies of difference equations (referred to as [Formula: see text]-systems) associated to the action of a (centrally extended, completed) infinite matrix group [Formula: see text] on [Formula: see text]-component fermionic Fock space. The solutions are given by matrix elements ([Formula: see text]-functions) for this action. We show that the [Formula: see text]-functions of type [Formula: see text] satisfy bilinear equations of length [Formula: see text]. The [Formula: see text]-system is, after a change of variables, the usual [Formula: see text] term [Formula: see text]-system of type [Formula: see text].

Restriction from [Formula: see text] to a subgroup isomorphic to the loop group [Formula: see text], defines [Formula: see text]-systems, studied earlier in [1] by the present authors for [Formula: see text].
Research on Age Estimation Algorithm Based on Structured Sparsity
Authors: Zhu Zijiang , Li Junshan , Hu Yi , Deng Xiaoguang
Published: October 2018

In order to solve the inaccuracy of age estimation dataset and the imbalance of age distribution, this paper proposes an age estimation model based on the structured sparse learning. Firstly, the Multi-label representation of facial images is performed by age, and the age estimation model is trained by solving the model matrix. Finally, the correlation with all age labels is calculated according to the facial images and age estimation model to be tested, and the most correlated age is taken as the predicted age. This paper sets up a series of verification experiments, and analyzes the structured sparse age estimation model from several perspectives. The proposed algorithm has achieved good results in the evaluation of indexes such as the mean absolute error, accumulation index curve and convergence rate, and has designed the demo system to put the model into use. Facts prove that the age estimation model proposed in this paper may achieve a good estimation effect.
Mean-field optimal multi-modes switching problem: A balance sheet
Authors: Eddahbi M’hamed , Fakhouri Imade , Ouknine Youssef
Published: October 2018

We study a finite horizon optimal multi-modes switching problem with many nodes. The switching is based on the optimal expected profit and cost yields, moreover both sides of the balance sheet are considered. The profit and cost yields per unit time are respectively assumed to be coupled through a coupling term which is the average of profit and cost yields. The corresponding system of Snell envelopes is highly complex, so we consider the aggregated yields where a mean-field approximation is used for the coupling term. First, the problem is formulated by the mean of the Snell envelope of processes. Then, in terms of backward SDEs, the problem is equivalent to a system of mean-field reflected backward SDEs with interconnected and nonlinear obstacles. More precisely, the driver function depends also on the mean of the unknown process (expected profit or cost yields) which makes the mean-field interaction in the driver nonlinear. The first main result of this paper, is to show the existence of a continuous minimal solution of the system of mean-field reflected backward SDEs, which is done by using the Picard iteration method. The second main result concerns the optimality of the switching strategies which we fully characterize.
Time-Varying Formation Control for Time-Delayed Multi-Agent Systems with General Linear Dynamics and Switching Topologies
Authors: Xiao Wei , Yu Jianglong , Wang Rui , Dong Xiwang , Li Qingdong , Ren Zhang
Published: October 2018

Time-varying formation analysis and design problems for general linear multi-agent systems with switching interaction topologies and time-varying delays are studied. Firstly, a consensus-based formation control protocol is constructed using local information of the neighboring agents. An algorithm with three steps is presented to design the proposed formation control protocol. Then, based on linear matrix inequality technique and common Lyapunove–Krasovskii stability theory, sufficient conditions for general linear multi-agent systems with switching topologies and time-varying delays to achieve time-varying formation are given together with a time-varying formation feasibility condition. Finally, a numerical simulation is given to demonstrate the effectiveness of the obtained theoretical results.
Tradeoffs in Neuroevolutionary Learning-Based Real-Time Robotic Task Design in the Imprecise Computation Framework
Authors: Huang Pei-Chi , Sentis Luis , Lehman Joel , Fok Chien-Liang , Mok Aloysius K. , Miikkulainen Risto
Published: October 2018

A cyberphysical avatar is a semi-autonomous robot that adjusts to an unstructured environment and performs physical tasks subject to critical timing constraints while under human supervision. This article first realizes a cyberphysical avatar that integrates three key technologies: body-compliant control, neuroevolution, and real-time constraints. Body-compliant control is essential for operator safety, because avatars perform cooperative tasks in close proximity to humans; neuroevolution (NEAT) enables “programming” avatars such that they can be used by non-experts for a large array of tasks, some unforeseen, in an unstructured environment; and real-time constraints are indispensable to provide predictable, bounded-time response in human-avatar interaction. Then, we present a study on the tradeoffs between three design parameters for robotic task systems that must incorporate at least three dimensions: (1) the amount of training effort for robot to perform the task, (2) the time available to complete the task when the command is given, and (3) the quality of the result of the performed task. A tradeoff study in this design space by using the imprecise computation as a framework is to perform a common robotic task, specifically, grasping of unknown objects. The results were validated with a real robot and contribute to the development of a systematic approach for designing robotic task systems that must function in environments like flexible manufacturing systems of the future.
Intersex, Hermaphroditism, and Gonadal Plasticity in Vertebrates: Evolution of the Müllerian Duct and Amh/Amhr2 Signaling
Authors: Adolfi Mateus Contar , Nakajima Rafael Takahiro , Nóbrega Rafael Henrique , Schartl Manfred
Published: October 2018

In vertebrates, sex organs are generally specialized to perform a male or female reproductive role. Acquisition of the Müllerian duct, which gives rise to the oviduct, together with emergence of the Amh/Amhr2 system favored evolution of viviparity in jawed vertebrates. Species with high sex-specific reproductive adaptations have less potential to sex reverse, making intersex a nonfunctional condition. Teleosts, the only vertebrate group in which hermaphroditism evolved as a natural reproductive strategy, lost the Müllerian duct during evolution. They developed for gamete release complete independence from the urinary system, creating optimal anatomic and developmental preconditions for physiological sex change. The common and probably ancestral role of Amh is related to survival and proliferation of germ cells in early and adult gonads of both sexes rather than induction of Müllerian duct regression. The relationship between germ cell maintenance and sex differentiation is most evident in species in which Amh became the master male sex–determining gene.
The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial
Authors: Myette-Côté Étienne , Durrer Cody , Neudorf Helena , Bammert Tyler D. , Botezelli José Diego , Johnson James D. , DeSouza Christopher A. , Little Jonathan P.
Published: October 2018

Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (−5%, P < 0.05), whereas both LC+Ex (−16%, P < 0.001) and LC (−12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: −32%, LC: −45%, and LC+Ex: −44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (−76%, P = 0.035) and a tendency for a reduction in LC (−70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (−27%, P = 0.001) and LC+Ex (−35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.
Role of connecting tubule glomerular feedback in obesity related renal damage
Authors: Monu Sumit R. , Maheshwari Mani , Peterson Edward L. , Carretero Oscar A.
Published: October 2018

Zucker obese rats (ZOR) have higher glomerular capillary pressure (PGC) that can cause renal damage. PGC is controlled by afferent (Af-Art) and efferent arteriole (Ef-Art) resistance. Af-Art resistance is regulated by factors that regulate other arterioles, such as myogenic response. In addition, it is also regulated by 2 intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that increased CTGF contributes to TGF attenuation, which in turn increases PGC in ZOR. We performed a renal micropuncture experiment and measured stop-flow pressure (PSF), which is an indirect measurement of PGC in ZOR. Maximal TGF response at 40 nl/min was attenuated in ZOR (4.47 ± 0.60 mmHg) in comparison to the Zucker lean rats (ZLR; 8.54 ± 0.73 mmHg, P < 0.05), and CTGF was elevated in ZOR (5.34 ± 0.87 mmHg) compared with ZLR (1.12 ± 1.28 mmHg, P < 0.05). CTGF inhibition with epithelial sodium channel blocker normalized the maximum PSF change in ZOR indicating that CTGF plays a significant role in TGF attenuation (ZOR, 10.67 ± 1.07 mmHg vs. ZLR, 9.5 ± 1.53 mmHg). We conclude that enhanced CTGF contributes to TGF attenuation in ZOR and potentially contribute to progressive renal damage.
Input-specific maturation of NMDAR-mediated transmission onto parvalbumin-expressing interneurons in layers 2/3 of the visual cortex
Authors: Ferrer Camilo , Hsieh Helen , Wollmuth Lonnie P.
Published: October 2018

Parvalbumin-expressing (PV) GABAergic interneurons regulate local circuit dynamics. In terms of the excitation driving PV interneuron activity, the N-methyl-d-aspartate receptor (NMDAR)-mediated component onto PV interneurons tends to be smaller than that onto pyramidal neurons but makes a significant contribution to their physiology and development. In the visual cortex, PV interneurons mature during the critical period. We hypothesize that during the critical period, the NMDAR-mediated signaling and functional properties of glutamatergic synapses onto PV interneurons are developmentally regulated. We therefore compared the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and NMDAR-mediated synaptic responses before (postnatal days 15–20, P15–P20), during (P25–P40), and after (P50–P60) the visual critical period. AMPAR miniature excitatory postsynaptic currents (mEPSCs) showed a developmental decrease in frequency, whereas NMDAR mEPSCs were absent or showed extremely low frequencies throughout development. For evoked responses, we consistently saw a NMDAR-mediated component, suggesting pre- or postsynaptic differences between evoked and spontaneous neurotransmission. Evoked responses showed input-specific developmental changes. For intralaminar inputs, the NMDAR-mediated component significantly decreased with development. This resulted in adult intralaminar inputs almost exclusively mediated by AMPARs, suited for the computation of synaptic inputs with precise timing, and likely having NMDAR-independent forms of plasticity. In contrast, interlaminar inputs maintained a stable NMDAR-mediated component throughout development but had a shift in the AMPAR paired-pulse ratio from depression to facilitation. Adult interlaminar inputs with facilitating AMPAR responses and a substantial NMDAR component would favor temporal integration of synaptic responses and could be modulated by NMDAR-dependent forms of plasticity.

NEW & NOTEWORTHY We show for the first time input-specific developmental changes in the N-methyl-d-aspartate receptor component and short-term plasticity of the excitatory drive onto layers 2/3 parvalbumin-expressing (PV) interneurons in the visual cortex during the critical period. These developmental changes would lead to functionally distinct adult intralaminar and interlaminar glutamatergic inputs that would engage PV interneuron-mediated inhibition differently.
Pluripotent Stem Cell-Derived Pancreatic Progenitors and β-Like Cells for Type 1 Diabetes Treatment
Authors: Sambathkumar Rangarajan , Migliorini Adriana , Nostro Maria Cristina
Published: October 2018

In this review, we focus on the processes guiding human pancreas development and provide an update on methods to efficiently generate pancreatic progenitors (PPs) and β-like cells in vitro from human pluripotent stem cells (hPSCs). Furthermore, we assess the strengths and weaknesses of using PPs and β-like cell for cell replacement therapy for the treatment of Type 1 diabetes with respect to cell manufacturing, engrafting, functionality, and safety. Finally, we discuss the identification and use of specific cell surface markers to generate safer populations of PPs for clinical translation and to study the development of PPs in vivo and in vitro.
The Difference δ-Cells Make in Glucose Control
Authors: Huising Mark O. , van der Meulen Talitha , Huang Jessica L. , Pourhosseinzadeh Mohammad S. , Noguchi Glyn M.
Published: October 2018

The role of beta and α-cells to glucose control are established, but the physiological role of δ-cells is poorly understood. Delta-cells are ideally positioned within pancreatic islets to modulate insulin and glucagon secretion at their source. We review the evidence for a negative feedback loop between delta and β-cells that determines the blood glucose set point and suggest that local δ-cell-mediated feedback stabilizes glycemic control.
Conflict and Compromise: Using Reversible Remodeling to Manage Competing Physiological Demands at the Fish Gill
Authors: Gilmour Kathleen M. , Perry Steve F.
Published: October 2018

The structural features of the fish gill necessary for oxygen uptake also favor undesirable, passive movements of ions and water. Reversible gill remodeling is one solution to this conflict. Cell masses that limit functional surface area are lost when oxygen availability decreases in hypoxia or oxygen demand increases with exercise or high temperature. However, much remains to be learned about how widespread reversible gill remodeling is among fish species, and how and why it occurs.
Technoeconomic Distribution Network Planning Using Smart Grid Techniques with Evolutionary Self‐Healing Network States
Authors: Nieto-Martin Jesus , Kipouros Timoleon , Savill Mark , Woodruff Jennifer , Butans Jevgenijs
Published: October 2018

The transition to a secure low‐carbon system is raising a set of uncertainties when planning the path to a reliable decarbonised supply. The electricity sector is committing large investments in the transmission and distribution sector upon 2050 in order to ensure grid resilience. The cost and limited flexibility of traditional approaches to 11 kV network reinforcement threaten to constrain the uptake of low‐carbon technologies. This paper investigates the suitability and cost‐effectiveness of smart grid techniques along with traditional reinforcements for the 11 kV electricity distribution network, in order to analyse expected investments up to 2050 under different DECC demand scenarios. The evaluation of asset planning is based on an area of study in Milton Keynes (East Midlands, United Kingdom), being composed of six 11 kV primaries. To undertake this, the analysis used a revolutionary new model tool for electricity distribution network planning, called scenario investment model (SIM). Comprehensive comparisons of short‐ and long‐term evolutionary investment planning strategies are presented. The work helps electricity network operators to visualise and design operational planning investments providing bottom‐up decision support.
Amino Acid-Based Metabolic Panel Provides Robust Prognostic Value Additive to B-Natriuretic Peptide and Traditional Risk Factors in Heart Failure
Authors: Wang Chao-Hung , Cheng Mei-Ling , Liu Min-Hui
Published: October 2018

Metabolic disturbances represent functional perturbation in peripheral tissues and predict outcomes in patients with heart failure (HF). This study developed an amino acid-based metabolic panel and sought to see whether this panel could add diagnostic and prognostic value to currently used B-type natriuretic peptide (BNP) measurements. Mass spectrometry and ultra-performance liquid chromatography were performed on 1288 participants, including 129 normal controls and 712 patients at HF stages A to D in the initial cohort and 447 stage C patients in the validation cohort. Patients were followed up for composite events (death/HF-related rehospitalization). Histidine, ornithine, and phenylalanine were 3 metabolites found strongly significant to identify patients at stage C and were adopted to develop the HOP panel. Compared to BNP, HOP had better value in discriminating the patients at different stages, especially in elderly patients and those with atrial fibrillation, high body mass index, or kidney dysfunction. HOP was correlated with the distance of 6 min walking distance better than BNP. For prognosis, HOP predicted composite events in patients at stages C and D, independent of log (BNP), age, sex, left ventricular ejection fraction, New York Heart Association functional class, HF stage, diabetes mellitus, chronic kidney disease, hypertension, hemoglobin, and albumin. Higher BNP (≥750 pg/mL) along with higher HOP (≥14) robustly predicted lower event-free survival compared to all others [hazard ratio=3.15 (2.23–4.46), p<0.001]. The prognostic value of HOP was confirmed in the validation cohort. In conclusion, aiming for clinical applications, this study proved that the HOP panel provides diagnostic and prognostic value additive to BNP and traditional risk factors.
Occurrence and Multilocus Genotyping of Giardia duodenalis in Yunnan Black Goats in China
Authors: Xie Shi-Chen , Zou Yang , Chen Dan , Jiang Meng-Meng , Yuan Xiao-Dan , Li Zhao , Zou Feng-Cai , Yang Jian-Fa , Sheng Jin-Liang , Zhu Xing-Quan
Published: October 2018

Giardia duodenalis is an important zoonotic parasite which can parasitize in the intestines of humans and various animals. However, the information about the prevalence and genetic diversity of G. duodenalis in goats in China is limited. It is yet to be known whether Yunnan black goats, a unique goat breed in subtropical Yunnan province, southwestern China, are infected with G. duodenalis. Thus, a total of 907 fecal samples were collected from Yunnan black goats in five regions in Yunnan province, to estimate the prevalence and genotypes of G. duodenalis using a PCR-based approach. The G. duodenalis prevalence is 4.2% (38/907) in Yunnan black goats by nested amplification of the β-giardin (bg) gene, and the genotypes are identified as assemblage E, with 5 novel subtypes (E11-E15). Multilocus sequence typing revealed that 11, 18, and 38 samples were amplifiable on tpi (triose phosphate isomerase), gdh (glutamate dehydrogenase), and bg locus, respectively, and identified three novel multilocus genotypes (MLGs): MLGE9-MLGE11. To our knowledge, this is the first report of G. duodenalis prevalence and genotypes in Yunnan black goats in China, which extended the host range of G. duodenalis and provided basic data for controlling G. duodenalis infection in Yunnan black goats.
Do MicroRNAs Modulate Visceral Pain?
Authors: Tao Zhuo-Ying , Xue Yang , Li Jin-Feng , Traub Richard J. , Cao Dong-Yuan
Published: October 2018

Visceral pain, a common characteristic of multiple diseases relative to viscera, impacts millions of people worldwide. Although hundreds of studies have explored mechanisms underlying visceral pain, it is still poorly managed. Over the past decade, strong evidence emerged suggesting that microRNAs (miRNAs) play a significant role in visceral nociception through altering neurotransmitters, receptors and other genes at the posttranscriptional level. Under pathological conditions, one kind of miRNA may have several target mRNAs and several kinds of miRNAs may act on one target, suggesting complex interactions and mechanisms between miRNAs and target genes lead to pathological states. In this review we report on recent progress in examining miRNAs responsible for visceral sensitization and provide miRNA-based therapeutic targets for the management of visceral pain.
Cellular and Molecular Heterogeneity Associated with Vessel Formation Processes
Authors: Castro Pollyana Ribeiro , Barbosa Alan Sales , Pereira Jousie Michel , Ranfley Hedden , Felipetto Mariane , Gonçalves Carlos Alberto Xavier , Paiva Isabela Ribeiro , Berg Bárbara Betônico , Barcelos Luciola Silva
Published: October 2018

The microvasculature heterogeneity is a complex subject in vascular biology. The difficulty of building a dynamic and interactive view among the microenvironments, the cellular and molecular heterogeneities, and the basic aspects of the vessel formation processes make the available knowledge largely fragmented. The neovascularisation processes, termed vasculogenesis, angiogenesis, arteriogenesis, and lymphangiogenesis, are important to the formation and proper functioning of organs and tissues both in the embryo and the postnatal period. These processes are intrinsically related to microvascular cells, such as endothelial and mural cells. These cells are able to adjust their activities in response to the metabolic and physiological requirements of the tissues, by displaying a broad plasticity that results in a significant cellular and molecular heterogeneity. In this review, we intend to approach the microvasculature heterogeneity in an integrated view considering the diversity of neovascularisation processes and the cellular and molecular heterogeneity that contribute to microcirculatory homeostasis. For that, we will cover their interactions in the different blood-organ barriers and discuss how they cooperate in an integrated regulatory network that is controlled by specific molecular signatures.
An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature
Authors: Miki Kosuke , Obara Naoshi , Makishima Kenichi , Sakamoto Tatsuhiro , Kusakabe Manabu , Kato Takayasu , Kurita Naoki , Nishikii Hidekazu , Yokoyama Yasuhisa , Sakata-Yanagimoto Mamiko , Hasegawa Yuichi , Chiba Shigeru
Published: October 2018

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.
Hydraulic Characteristics of Transporting a Piped Carriage in a Horizontal Pipe Based on the Bidirectional Fluid-Structure Interaction
Authors: Zhang Chunjin , Sun Xihuan , Li Yongye , Zhang Xueqin , Zhang Xuelan , Yang Xiaoni , Li Fei
Published: October 2018

Energy shortage restricts the rapid development of the global transport industry. Trying to develop innovative modes of transport becomes an inevitable trend. Hydraulic Capsule Pipelines (HCPs) are the freight transportation modes that use a kind of fluid to push capsules filled with bulk solids materials through water-filled pipelines. HCPs not only alleviate everincreasing costs caused by energy scarcities and oil price up, but also solve issues like traffic congestion and environmental pollution. Published literature is mainly limited to numerical simulation of the unidirectional fluid-structure interaction between the capsules and the fluid inside the pipelines; furthermore, the hydraulic characteristics only involve the speed of the capsules and the pressure drop characteristics of the fluid within the pipe. This research was conducted on the following four aspects of HCPs. First, an improved cylindrical capsule called a “piped carriage” was evaluated. Second, an associated solution between the fluid domain within the pipe and the solid domain of the piped carriage was investigated numerically on the basis of the bidirectional fluid-structure interaction methods. Third, the effects of diameter ratiob(ratio of a diameter of the piped carriageDeto a pipe diameterDp, widely ranging inb=0.4~0.95) on hydraulic characteristics of transporting the piped carriage within the pipeline were extensively discussed. Finally, based on Least-Cost Principle, an optimization model of HCPs was effectively built. The results showed that the simulated results were in good agreement with the experimental results, which further indicated that it was feasible for solving the hydraulic characteristics of transporting the piped carriage by using the bidirectional fluid-structure interaction methods. The results will be of great reference value for further research on HCPs and also provide a theoretical foundation for the optimal design of HCPs.
Comprehensive Validation of Snapback Primer-Based Melting Curve Analysis to Detect Nucleotide Variation in the Codon 12 and 13 of KRAS Gene
Authors: Zhang Qunfeng , Du Yiqiao , Zhang Xinju , Kang Zhihua , Guan Ming , Wu Zhiyuan
Published: October 2018

Background. KRAS genotyping in tumor samples is a decisive clinical test for the anti-EGFR therapy management. However, the complexity of KRAS mutation landscape across different cancer types and the mosaic effect caused by cancer cellularity and heterogeneity make the choice of KRAS genotyping method a challenging topic in the clinical practice. Methods. We depicted the landscape of somatic KRAS mutation in 7,844 primary tumors and 10,336 metastatic tumors across over 30 types of cancer using the Cancer Genome Atlas (TCGA) and Integrated Mutation Profiling of Actionable Cancer Targets (MSKCC-IMPACT) databases, respectively. A snapback primer assay based on melting curve analysis was developed to detect the most common somatic mutations in KRAS codons 12 and 13. The sensitivity and accuracy of the method was validated by genotyping 100 colorectal cancer (CRC) samples, in comparison with Sanger sequencing and T-A cloning sequencing. Results. Pancreas adenocarcinoma (somatic mutation frequency 90.6%), colorectal adenocarcinoma (42.5%), and lung adenocarcinoma (32.6%) are the top three most KRAS mutant primary cancer types. The metastatic tumors showed a higher prevalence (90.99% versus 66.31%) and diversity of KRAS mutation compared with the primary tumors. Mutations in codons 12 and 13 are the predominant genetic alteration in KRAS (84.15% for TCGA and 86.13% for MSK-IMPACT). Moreover, KRAS mutation is highly correlated with the overall survival of patients with metastatic cancer. The snapback primer assay showed a more favorable performance in enriching and detecting the KRAS codon 12 and 13 mutation (1% mutation load) compared with Sanger sequencing (20% mutation load and 7% false-negative rate). Conclusions. KRAS mutation pattern is highly diverse among different cancer types and is associated with the survival of patients with metastatic cancers. The snapback primer assay is a reliable, sensitive method to detect the major mutant KRAS alleles, which might facilitate the effective cancer treatment decisions.
Wardowski Type Contractions and the Fixed-Circle Problem on S-Metric Spaces
Authors: Mlaiki Nabil , Çelik Ufuk , Taş Nihal , Özgür Nihal Yilmaz , Mukheimer Aiman
Published: October 2018

In this paper, we present new fixed-circle theorems for self-mappings on an S-metric space using some Wardowski type contractions, ψ-contractive, and weakly ψ-contractive self-mappings. The common property in all of the obtained theorems for Wardowski type contractions is that the self-mapping fixes both the circle and the disc with the center x0 and the radius r.
Genetic Markers Can Predict Chondrogenic Differentiation Potential in Bone Marrow-Derived Mesenchymal Stromal Cells
Authors: Kanawa Masami , Igarashi Akira , Fujimoto Katsumi , Higashi Yukihito , Kurihara Hidemi , Sugiyama Masaru , Saskianti Tania , Kato Yukio , Kawamoto Takeshi
Published: October 2018

The precise predictions of the differentiation direction and potential of mesenchymal stromal cells (MSCs) are an important key to the success of regenerative medicine. The expression levels of fate-determining genes may provide tools for predicting differentiation potential. The expression levels of 95 candidate marker genes and glycosaminoglycan (GAG) contents after chondrogenic induction in 10 undifferentiated ilium and 5 jaw MSC cultures were determined, and their correlations were analyzed. The expression levels of eight genes before the induction of chondrogenic MSC differentiation were significantly correlated with the GAG levels after induction. Based on correlation patterns, the eight genes were classified into two groups: group 1 genes (AURKB,E2F1,CDKN2D,LIF, andACLY), related to cell cycle regulation, and group 2 genes (CD74,EFEMP1, andTGM2), involved in chondrogenesis. The expression levels of the group 2 genes were significantly correlated with the ages of the cell donors. The expression levels ofCDKN2D,CD74, andTGM2were >10-fold higher in highly potent MSCs (ilium MSCs) than in MSCs with limited potential (jaw MSCs). Three-dimensional (3D) scatter plot analyses of the expression levels of these genes showed reduced variability between donors and confirmed predictive potential. These data suggest that group 2 genes are involved in age-dependent decreases in the chondrogenic differentiation potential of MSCs, and combined 3D analyses of the expression profiles of three genes, including two group 2 genes, were predictive of MSC differentiation potential.
Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling
Authors: Luo Yong-Heng , Chen Juan , Xiao En-Hua , Li Qiu-Yun , Luo Yong-Mei
Published: October 2018

Demethylating agent zebularine is reported to be capable of inducing differentiation of stem cells by activation of methylated genes, though its function in hepatocyte differentiation is unclear. p38 signal pathway is involved in differentiation of hepatocytes and regulating of DNA methyltransferases 1 (DNMT1) expression. However, little is known about the impact of zebularine on bone marrow mesenchymal stem cells (BMMSCs) and p38 signaling during hepatic differentiation. The present study investigated the effects of zebularine on hepatic differentiation of rabbit BMMSCs, as well as the role of p38 on DNMT1 and hepatic differentiation, with the aim of developing a novel strategy for improving derivation of hepatocytes. BMMSCs were treated with zebularine at concentrations of 10, 20, 50, and 100 μM in the presence of hepatocyte growth factor; changes in the levels of hepatic-specific alpha-fetoprotein and albumin were detected and determined by RT-PCR, WB, and immunofluorescence staining. Expression of DNMT1 and phosphorylated p38 as well as urea production and ICG metabolism was also analyzed. Zebularine at concentrations of 10, 20, and 50 μM could not affect cell viability after 48 h. Zebularine treatment leads to an inhibition of DNMT activity and increase of hepatic-specific proteins alpha-fetoprotein and albumin in BMMSCs in vitro; zebularine addition also induced expression of urea production of and ICG metabolism. p38 signal was activated in BMMSCs simulated with HGF; inhibition of p38 facilitated the synthesis of DNMT1 and albumin in cells. Zebularine restrained DNMT1 and phosphorylated p38 which were induced by HGF. Therefore, this study demonstrated that treatment with zebularine exhibited terminal hepatic differentiation of BMMSCs in vitro in association with hepatocyte growth factor; p38 pathway at least partially participates in zebularine-induced hepatic differentiation of rabbit BMMSCs.
First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study
Authors: Boutin Amélie , Demers Suzanne , Gasse Cédric , Giguère Yves , Tétu Amélie , Laforest Geneviève , Bujold Emmanuel
Published: October 2018

Background: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. Subjects and Methods: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11–13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). Results: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57–0.65) and preterm PE (AUC = 0.73, 95% CI 0.64–0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62–0.71; AUC for preterm PE 0.81, 95% CI 0.72–0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. Conclusion: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.
The Effects of Gusher-Related Intracochlear Pressure Changes on Hearing Preservation in Cochlear Implantation: A Comparative Series
Authors: Crohan William , Krishnaswamy Jay , Rajan Gunesh
Published: October 2018

Aim: To investigate and compare residual hearing preservation between patients based on the presence of intraoperative gusher. Methodology: We retrospectively compared 2 cohorts of cochlear implant recipients significantly distinguished by whether or not they experienced gusher intraoperatively. Patients underwent cochlear implantation using 24-mm lateral wall electrode arrays as well pharmacologic steroid protection. All patients were assessed by a hearing implant MDT. Hearing preservation rates and speech perception outcomes were assessed at 1, 6, 12, 24, 36, 48, and 60 months. Results: The patients with no gusher demonstrated complete hearing preservation. The patients with gusher demonstrated significant postoperative reduction of hearing thresholds, which declined at a significantly higher pace during follow-up. All patients demonstrated significantly better speech performance after cochlear implantation. Conclusion: The present study suggests that intraoperative gusher is associated with a significant drop in residual hearing, both immediately and over time, which may be related to the large change in intracochlear pressure intraoperatively.
Chemoreduction of Orbital Recurrence of Uveal Melanoma by Intra-Arterial Melphalan
Authors: Francis Jasmine H. , Barker Christopher A. , Yin Vivian T. , Carvajal Richard D. , Chapman Paul , Abramson David H. , Gobin Y. Pierre
Published: October 2018

Background/Aims: The treatment of orbital melanoma poses a management challenge. This case explores the delivery of high-dose melphalan to an orbital recurrence of uveal melanoma via intra-arterial delivery of melphalan to the orbit. A 62-year-old man developed recurrent orbital disease 7 months after enucleation for a large uveal melanoma. He received 6 monthly intra-arterial infusions of melphalan to the orbit, ranging in dose from 20 to 30 mg per infusion. Following the last infusion, mild temporary erythema was noted on the forehead along the distribution of the supratrochlear artery. The orbital recurrence was reduced in size by 66% in the longest dimension as measured by magnetic resonance imaging (MRI). However, 9 months following intra-arterial melphalan, tumor regrowth was detected on MRI, and additional treatment options were pursued. Conclusion: This case demonstrates that intra-arterial melphalan can result in nonsustained tumor regression of recurrent orbital uveal melanoma. It suggests that local delivery of high-dose melphalan may be helpful as a neoadjuvant treatment for uveal melanoma, and future studies will be useful to confirm the value of this approach in additional cases of recurrent and possibly in primary uveal melanoma.