bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences with obtaining informed consent for genomic sequencing
Authors: Bernhardt Barbara A. , Roche Myra I. , Perry Denise L. , Scollon Sarah R. , Tomlinson Ashley N. , Skinner Debra
Published: July 2015

Despite the increased utilization of genome and exome sequencing, little is known about the actual content and process of informed consent for sequencing. We addressed this by interviewing 29 genetic counselors and research coordinators experienced in obtaining informed consent for sequencing in research and clinical settings. Interviews focused on the process and content of informed consent; patients/participants' common questions, concerns and misperceptions; and challenges to obtaining informed consent. Content analysis of transcribed interviews revealed that the main challenges to obtaining consent related to the broad scope and uncertainty of results, and patient/participants' unrealistic expectations about the likely number and utility of results. Interviewees modified their approach to sessions according to contextual issues surrounding the indication for testing, type of patient, and timing of testing. With experience, most interviewees structured sessions to place less emphasis on standard elements in the consent form and technological aspects of sequencing. They instead focused on addressing misperceptions and helping patients/participants develop realistic expectations about the types and implications of possible results, including secondary findings. These findings suggest that informed consent sessions should focus on key issues that may be misunderstood by patients/participants. Future research should address the extent to which various stakeholders agree on key elements of informed consent. © 2015 Wiley Periodicals, Inc.
Detection of mutually exclusive mosaicism in a girl with genotype‐phenotype discrepancies
Authors: Luo Minjie , Mulchandani Surabhi , Dubbs Holly A. , Swarr Daniel , Pyle Louise , Zackai Elaine H. , Spinner Nancy B. , Conlin Laura K.
Published: July 2015

Discordance between clinical phenotype and genotype has multiple causes, including mosaicism. Phenotypes can be modified due to tissue distribution, or the presence of multiple abnormal cell lines with different genomic contributions. We have studied a 20‐month‐old female whose main phenotypes were failure to thrive, developmental delay, and patchy skin pigmentation. Initial chromosome and SNP microarray analysis of her blood revealed a non‐mosaic ∼24 Mb duplication of 15q25.1q26.3 resulting from the unbalanced translocation of terminal 15q to the short arm of chromosome 15. The most common feature associated with distal trisomy 15q is prenatal and postnatal overgrowth, which was not consistent with this patient's phenotype. The phenotypic discordance, in combination with the patchy skin pigmentation, suggested the presence of mosaicism. Further analysis of skin biopsies from both hyper‐ and hypopigmented regions confirmed the presence of an additional cell line with the short arm of chromosome X deleted and replaced by the entire long arm of chromosome 15. The Xp deletion, consistent with a variant Turner Syndrome diagnosis, better explained the patient's phenotype. Parental studies revealed that the alterations in both cell lines were de novo and the duplicated distal 15q and the deleted Xp were from different parental origins, suggesting a mitotic event. The possible mechanism for the occurrence of two mutually exclusive structural rearrangements with both involving the long arm of chromosome 15 is discussed. © 2015 Wiley Periodicals, Inc.
Dark energy in light of the discovery of the Higgs
Authors: Copeland Edmund J.
Published: July 2015

We discuss the impact the observation of the Higgs Boson has had on models of Dark Energy.
Fabrication of polyvinyl chloride based nanocomposite nanofiltration membrane: investigation of SDS/Al2O3 nanoparticle concentration and solvent ratio effects
Authors: Bagheripour E. , Moghadassi A. R. , Hosseini S. M.
Published: July 2015

In the current research polyvinylchloride‐based nanocomposite nanofiltration membranes were prepared by using of sodium dodecyl sulfate (SDS) as additive, aluminum oxide (Al2O3) nanoparticles as inorganic filler and dimethylacetamide (DMAC)/tetrahydrofuran (THF) as solvents via phase inversion method. The effect of solvents ratio (DMAC to THF), SDS concentration and Al2O3 nanoparticle concentration in the casting solution on membrane physico‐chemical properties was studied. The flux, selectivity and water content measurements and also scanning electron microscope analysis were carried out for the membrane characterization. The increase of THF concentration in the casting solution led to decrease of membrane flux and increase of salt rejection. Additionally, flux was reduced, and rejection was enhanced by utilizing of SDS in the casting solution significantly. Furthermore, membrane flux was improved initially and then declined by increase of Al2O3 nanoparticle content ratio in membrane matrix. This was followed by nearly constant trend of rejection by increase of nanoparticle concentration. The optimum concentrations of used SDS and Al2O3 nanoparticles and solvent (DMAC:THF) ratio were found 0.45 %wt, 0.05 %wt and (85:15) (V/V) respectively. © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.
Effect of graphene oxide on the behavior of poly(amide‐6‐b‐ethylene oxide)/graphene oxide mixed‐matrix membranes in the permeation process
Authors: Zhao Dan , Ren Jizhong , Qiu Yongtao , Li Hui , Hua Kaisheng , Li Xinxue , Deng Maicun
Published: July 2015

Polyether‐block‐amide (Pebax)/graphene oxide (GO) mixed‐matrix membranes (MMMs) were prepared with a solution casting method, and their gas‐separation performance and mechanical properties were investigated. Compared with the pristine Pebax membrane, the crystallinity of the Pebax/GO MMMs showed a little increase. The incorporation of GO induced an increase in the elastic modulus, whereas the strain at break and tensile strength decreased. The apparent activation energies (Ep) of CO2, N2, H2, and CH4 permeation through the Pebax/GO MMMs increased because of the greater difficulty of polymer chain rotation. The Ep value of CO2 changed from 16.5 kJ/mol of the pristine Pebax to 23.7 kJ/mol of the Pebax/GO MMMs with 3.85 vol % GO. Because of the impermeable nature of GO, the gas permeabilities of the Pebax/GO MMMs decreased remarkably with increasing GO content, in particular for the larger gases. The CO2 permeability of the Pebax/GO MMMs with 3.85 vol % GO decreased by about 70% of that of the pristine Pebax membrane. Rather than the Maxwell model, the permeation properties of the Pebax/GO MMMs could be described successfully with the Lape model, which considered the influence of the geometrical shape and arrangement pattern of GO on the gas transport. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42624.
Electrochemical behavior of multifunctional graphene–polyimide nanocomposite film in two different electrolyte solutions
Authors: Okafor Patricia Azuka , Huxel Brenton , Iroh Jude O.
Published: July 2015

The effect of solvent on specific capacitance, bulk resistance, and charge/discharge capacity of graphene/polyimide composite films is studied by electrochemical methods. Composite films are synthesized by in situ condensation polymerization of poly (amic acid) in the presence of 50 wt % partly exfoliated graphene sheets followed by thermal curing at 250°C. Raman spectrum of the exfoliated graphene sheets show an increase in the ratio of ID to IG peak intensities from 0.167 to 0.222, suggesting increased defects in graphene basal planes. Electrochemical measurements carried out by using 0.4M potassium hexafluorophosphate (KPF6) dissolved in propylene carbonate and N‐methylpyrrolidone at 25°C show that the composite system exhibits both pseudocapacitance and supercapacitance behaviors, with an average capacitance of 40 and 36.5 F g−1, respectively. Bulk resistance of the composite obtained by using KPF6–propylene carbonate electrolyte solution is 300% lower than that obtained in KPF6–N‐methylpyrrolidone solution, with a fairly stable specific capacity of 85 μAhr g−1, with 80% retention observed after 30 charge–discharge cycles. Fourier transform infrared spectroscopy measurements show shifts in the cyclic imide carbonyl peak from 1778 to 1774 cm−1, which suggests that some form of interaction exists between the graphene and polyimide. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42673.
Preparation and Electrochemical Properties of Tin–Iron–Carbon Nanocomposite as the Anode of Lithium‐Ion Batteries
Authors: Yang Xu , Zhang Rongyu , Bie Xiaofei , Wang Chunzhong , Li Malin , Chen Nan , Wei Yingjin , Chen Gang , Du Fei
Published: July 2015

Tin–iron–carbon nanocomposite is successfully prepared by a sol–gel method followed by a chemical vapor deposition (CVD) process with acetylene gas as the carbon source. The structural properties, morphology, and electrochemical performances of the nanocomposite are comprehensively studied in comparison with those properties of tin–carbon and iron–carbon nanocomposites. Sheet‐like carbon architecture and different carbon contents are induced thanks to the catalytic effect of iron during CVD. Among three nanocomposites, tin–iron–carbon demonstrates the highest reversible capacity of 800 mA h g−1 with 96.9 % capacity retention after 50 cycles. It also exhibits the best rate capability with a discharge capacity of 420 mA h g−1 at a current density of 1000 mA g−1. This enhanced performance is strongly related to the carbon morphology and content, which can not only accommodate the large volume change, but also improve the electronic conductivity of the nanocomposite. Hence, the tin–iron–carbon nanocomposite is expected to be a promising anode for lithium‐ion batteries.
A Direct, Concise, and Enantioselective Synthesis of 2‐Substituted 4,4,4‐Trifluorobutane‐1,3‐diols Based on the Organocatalytic In Situ Generation of Unstable Trifluoroacetaldehyde
Authors: Funabiki Kazumasa , Furuno Yudai , Yano Yosuke , Sakaida Yuta , Kubota Yasuhiro , Matsui Masaki
Published: July 2015

A direct, concise, and enantioselective synthesis of 2‐substituted 4,4,4‐trifluorobutane‐1,3‐diols based on the organocatalytic asymmetric direct aldol reaction of an ethyl hemiacetal of trifluoroacetaldehyde with various aldehydes was examined. A catalytic amount (30 mol %) of commercially available and inexpensive l‐prolinamide is quite effective as an organocatalyst for the catalytic in situ generation of gaseous and unstable trifluoroacetaldehyde from its hemiacetal, and a successive asymmetric direct aldol reaction with various aldehydes in dichloromethane at 0 °C, followed by reduction with sodium borohydride, gives 2‐substituted 4,4,4‐trifluorobutane‐1,3‐diols in moderate to good yields (31–84 %) with low diastereoselectivities and good to excellent enantioselectivities (64–97 % ee).
Modulation of Energy Conversion Processes in Carbonaceous Molecular Bearings
Authors: Hitosugi Shunpei , Ohkubo Kei , Kawashima Yuki , Matsuno Taisuke , Kamata Sho , Nakamura Kosuke , Kono Hirohiko , Sato Sota , Fukuzumi Shunichi , Isobe Hiroyuki
Published: July 2015

The energetics and photodynamics of carbonaceous molecular bearings with discrete molecular structures were investigated. A series of supramolecular bearings comprising belt‐persistent tubular cycloarylene and fullerene molecules accepted photonic stimuli to afford charge‐separated species via a photoinduced electron transfer process. The energy conversion processes associated with the photoexcitation, however, differed depending on the molecular structure. A π‐lengthened tubular molecule allowed for the emergence of an intermediary triplet excited state at the bearing, which should lead to an energy conversion to thermal energy. On the other hand, low‐lying charge‐separated species induced by an endohedral lithium ion in fullerene enabled back electron transfer processes to occur without involving triplet excited species. The structure–photodynamics relationship was analyzed in terms of the Marcus theory to reveal a large electronic coupling in this dynamic supramolecular system.
Energetic Materials Based on 5,5′‐Diamino‐4,4′‐dinitramino‐3,3′‐bi‐1,2,4‐triazole
Authors: Klapötke Thomas M. , Leroux Marcel , Schmid Philipp C. , Stierstorfer Jörg
Published: July 2015

A simple and straightforward synthesis of 5,5′‐diamino‐4,4′‐dinitramino‐3,3′‐bi‐1,2,4‐triazole by the selective nitration of 4,4′,5,5′‐tetraamino‐3,3′‐bi‐1,2,4‐triazole is presented. The interaction of the amino and nitramino groups improves the energetic properties of this functionalized bitriazole. For a deeper investigation of these properties, various nitrogen‐rich derivatives were synthesized. The new compounds were investigated and characterized by spectroscopy (1H and 13C NMR, IR, Raman), elemental analysis, mass spectrometry, differential thermal analysis (DTA), X‐ray analysis, and impact and friction sensitivities (IS, FS). X‐ray analyses were performed and deliver insight into structural characteristics with which the stability of the compounds can be explained. The standard enthalpies of formation were calculated for all compounds at the CBS‐4M level of theory, revealing highly positive heats of formation. The energetic performance of the new molecules was predicted with the EXPLO5 V6.02 computer. A small‐scale shock reactivity test (SSRT) and a toxicity test gave a first impression of the performance and toxicity of selective compounds.
Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness
Authors: Sellick Christopher A. , Croxford Alexandra S. , Maqsood Arfa R. , Stephens Gill M. , Westerhoff Hans V. , Goodacre Royston , Dickson Alan J.
Published: July 2015

Whilst development of medium and feeds has provided major advances in recombinant protein production in CHO cells, the fundamental understanding is limited. We have applied metabolite profiling with established robust (GC‐MS) analytics to define the molecular loci by which two yield‐enhancing feeds improve recombinant antibody yields from a model GS‐CHO cell line. With data across core metabolic pathways, that report on metabolism within several cellular compartments, these data identify key metabolites and events associated with increased cell survival and specific productivity of cells. Of particular importance, increased process efficiency was linked to the functional activity of the mitochondria, with the amount and time course of use/production of intermediates of the citric acid cycle, for uses such as lipid biosynthesis, precursor generation and energy production, providing direct indicators of cellular status with respect to productivity. The data provide clear association between specific cellular metabolic indicators and cell process efficiency, extending from prior indications of the relevance of lactate metabolic balance to other redox sinks (glycerol, sorbitol and threitol). The information, and its interpretation, identifies targets for engineering cell culture efficiency, either from genetic or environmental perspectives, and greater understanding of the significance of specific medium components towards overall CHO cell bioprocessing.
Intraoperative detection of sentinel lymph node metastases in breast carcinoma by Fourier transform infrared spectroscopy
Authors: Tian P , Zhang W , Zhao H , Lei Y , Cui L , Zhang Y , Xu Z
Published: July 2015

Background

Sentinel lymph node (SLN) biopsy is a routine surgical staging procedure in clinically lymph node-negative breast cancer. Fourier transform infrared (FTIR) spectroscopy, a technique based on the biochemical composition of the tissue, has previously been found to be capable of differentiating between normal and malignant tissue. The aim of the present study was to explore the intraoperative use of FTIR spectroscopy for rapidly identifying metastatic SLNs, and distinguishing between metastatic and non-metastatic tissue.

Methods

Freshly removed SLNs from patients with breast cancer were analysed. Samples were measured by FTIR spectroscopy before histopathological diagnosis. The FTIR spectrum of each sample identified ten bands from 2000 to 900 cm−1. The peak position, intensity and full width at half maximum of each absorbent band were measured, and the relative intensity ratios calculated. Canonical discriminant analysis was performed to discriminate between metastatic and non-metastatic samples.

Results

A total of 149 SLNs were removed from 49 patients. Histopathological examination confirmed 38 metastatic and 111 non-metastatic SLNs. Eighteen of 29 parameters were significantly different between the metastatic and non-metastatic SLNs. Five parameters were selected as independent factors to form discriminant functions. The sensitivity, specificity and accuracy of this method were 94·7, 90·1 and 91·3 per cent respectively. The accuracy of histological analysis of frozen sections was 100 per cent.

Conclusion

FTIR spectroscopy is a promising technique for the real-time diagnosis of SLN metastasis during breast cancer surgery. Surgical relevanceSentinel lymph node (SLN) biopsy is a highly accurate predictor of overall axillary status and has become the standard in disease staging in clinically node-negative breast cancer. A rapid and accurate intraoperative assessment of metastatic spread to the SLN provides the necessary information for the surgeon to proceed with immediate axillary dissection.The results of this research indicate that Fourier transform infrared (FTIR) spectroscopy is a rapid, accurate, non-destructive and cost-effective molecular method that can be used to detect SLN metastasis during surgery.FTIR analysis could be useful for the intraoperative diagnosis of lymph node metastases at large institutions, thereby reducing the workload of pathologists, as well as in regions lacking pathologists such as in developing countries.
Impact of bacterial contamination of the abdominal cavity during pancreaticoduodenectomy on surgical-site infection
Authors: Sugiura T , Mizuno T , Okamura Y , Ito T , Yamamoto Y , Kawamura I , Kurai H , Uesaka K
Published: July 2015

Background

Several risk factors for complications after pancreaticoduodenectomy have been reported. However, the impact of intraoperative bacterial contamination on surgical outcome after pancreaticoduodenectomy has not been examined in depth.

Methods

This retrospective study included patients who underwent pancreaticoduodenectomy and peritoneal lavage using 7000 ml saline between July 2012 and May 2014. The lavage fluid was subjected to bacterial culture examination. The influence of a positive bacterial culture on surgical-site infection (SSI) and postoperative course was evaluated. Risk factors for positive bacterial cultures were also evaluated.

Results

Forty-six (21·1 per cent) of 218 enrolled patients had a positive bacterial culture of the lavage fluid. Incisional SSI developed in 26 (57 per cent) of these 46 patients and in 13 (7·6 per cent) of 172 patients with a negative lavage culture (P < 0·001). Organ/space SSI developed in 32 patients with a positive lavage culture (70 per cent) and in 43 of those with a negative culture (25·0 per cent) (P < 0·001). Grade B/C pancreatic fistula was observed in 22 (48 per cent) and 48 (27·9 per cent) respectively of patients with positive and negative lavage cultures (P = 0·010). Postoperative hospital stay was longer in patients with a positive lavage culture (28 days versus 21 days in patients with a negative culture; P = 0·028). Multivariable analysis revealed that internal biliary drainage, combined colectomy and a longer duration of surgery were significant risk factors for positive bacterial culture of the lavage fluid.

Conclusion

Intraoperative bacterial contamination has an adverse impact on the development of SSI and grade B/C pancreatic fistula following pancreaticoduodenectomy.
Application of N‐substituted (aminomethyl)benzoate Strategy in Design of Scutellarein Derivatives with Improved Caco‐2 Cell Permeability and In Vitro Antioxidative Activity
Authors: Dai Ze‐Qin , Su Hang , Luo Min , Ou Yu , Fu Xiao‐Zhong , Dong Yong‐Xi , Cha Yu‐Feng , Zhang Shun , Huang Yong , Wang Yong‐Lin
Published: July 2015

A series of 4′‐N‐substituted (aminomethyl)benzoate derivatives of scutellarein were designed and synthesized. Evaluation of their physiochemical properties showed that the designed target compounds 5a–e exhibit higher chemical stability and aqueous solubility than scutellarin and scutellarein. The permeability (P
app
AP
to
BL
) of 5c–e in Caco‐2 cells were 2.8, 8.1, and 12.6 times higher than that of scutellarin and 1.3, 4.1, and 6.0 times higher than that of scutellarein; especially, 5e had the highest P
app
AP
to
BL
value (7.19 ± 0.31 × 10−6 cm/s) and the lowest ER (P
app
BL
to
AP
/P
app
AP
to
BL
) value of 0.17. In vitro antioxidative evaluation results revealed that 5e could protect against H2O2
‐induced PC12 cells’ oxidative damage by attenuating mitochondrial membrane potential loss and decreasing H2O2
‐induced reactive oxygen species (ROS) production.
Developing Rapport with Children in Forensic Interviews: Systematic Review of Experimental Research
Authors: Saywitz Karen J. , Larson Rakel P. , Hobbs Sue D. , Wells Christine R.
Published: July 2015

The vast majority of guidelines recommend that developing rapport with children is essential for successful forensic child interviewing; however, the question remains as to whether there is a sufficient body of scientific research to generate evidence‐based guidelines for developing rapport with children in legal contexts. To answer this question, we conducted a systematic review of the literature to identify experimental studies of the effects of rapport‐building methods on the reliability of children's reports. Independent raters applied 12 exclusion criteria to the 2,761 potentially relevant articles located by electronic and hand searches of the literature. Experimental studies were few. Although studies to date are a beginning, the overall scientific base is weak regarding even basic issues such as how to best define rapport and the efficacy of common rapport‐building techniques. This systematic review highlights what we know, what we do not know, and how much more we need to know to create evidence‐based best practice. Recommendations for reshaping the research agenda are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Length of Time to Resolve Criminal Charges of Child Sexual Abuse: A Three‐County Case Study
Authors: Walsh Wendy A. , Lippert Tonya , Edelson Meredyth Goldberg , Jones Lisa M.
Published: July 2015

The present study sought to examine the court culture of three Oregon counties and their timelines for resolving felony child sexual abuse cases. Specifically, we examined (a) case outcomes, churning (i.e., the extent to which four court events were rescheduled), the length of time to reach a criminal case resolution, and how this length of time compared to that for felonies generally; (b) whether mandatory minimum sentences affected resolution timeliness; and (c) key stakeholders’ perceptions about their local court culture. Data included retrospective case‐file abstraction (N = 532) on all felony child sex crimes for a 2‐year period and interviews with legal professionals (N = 23). Across all three counties, a minority of child sexual abuse cases (18% to 47%) were resolved within the target timeframe of 4 months. In contrast, most felonies (65% to 77%) were resolved within this timeframe. The rescheduling of trials and the requirement of mandatory minimum sentences for some felony child sexual abuse crimes increased the time until case resolution. Results suggest that court cultures that are hierarchical and cooperative may lead to longer case resolution times than court cultures that are self‐managing or autonomous. Implications of these results and other results are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Src family kinases maintain the balance between replication stress and the replication checkpoint
Authors: Miura Takahito , Fukumoto Yasunori , Morii Mariko , Honda Takuya , Yamaguchi Noritaka , Nakayama Yuji , Yamaguchi Naoto
Published: July 2015

Progression of DNA replication is tightly controlled by replication checkpoints to ensure the accurate and rapid duplication of genetic information. Upon replication stress, the replication checkpoint slows global DNA replication by inhibiting the late‐firing origins and by slowing replication fork progression. Activation of the replication checkpoint has been studied in depth; however, little is known about the termination of the replication checkpoint. Here, we show that Src family kinases promote the recovery from replication checkpoints. shRNA knockdown of a Src family kinase, Lyn, and acute chemical inhibition of Src kinases prevented inactivation of Chk1 after removal of replication stress. Consistently, Src inhibition slowed resumption of DNA replication, after the removal of replication blocks. The effect of Src inhibition was not observed in the presence of an ATM/ATR inhibitor caffeine. These data indicate that Src kinases promote the resumption of DNA replication by suppressing ATR‐dependent replication checkpoints. Surprisingly, the resumption of replication was delayed by caffeine. In addition, Src inhibition delayed recovery from replication fork collapse. We propose that Src kinases maintain the balance between replication stress and the activity of the replication checkpoint.
Non‐cardiac procedures after DES: An everyday issue awaiting answers
Authors: Esteves Vinícius , Lemos Pedro A.
Published: July 2015

Key Points

Need for non-cardiac surgery is a common event during the follow-up of patients treated drug-eluting stenting.

The eventual associated risks of complications (bleeding and stent thrombosis) are relatively low.

Larger clinical studies are needed to better delineate the optimal management of this population.
Stent edge dissection: Depth of injury and adverse outcome
Authors: Goldstein James A.
Published: July 2015

Key Points

Deep stent edge dissection by OCT predicts adverse outcome

STEMI culprit lesions are most susceptible to edge dissection

Procedural performance influences edge dissection
Drug‐coated balloons—the importance of packing and dosing antiproliferative drugs
Authors: Hehrlein Christoph
Published: July 2015

Key Points

Several balloon catheters coated with paclitaxel have been shown to reduce restenosis rates in the superficial femoral artery (SFA) revealing a relatively wide therapeutic window of effective doses ranging from 2 to 3 µg/mm2 balloon surface area

Delivering lower antiproliferative drug doses to the vessel wall may not be inferior to higher drug doses provided that effective drug‐excipient formulations have been chosen

Leaving non‐flow limiting dissection in the SFA non‐stented might be an option after use of drug‐coated balloons
Transcatheter aortic valve implantation for bicuspid aortic valve stenosis
Authors: Hamdan Ashraf , Kornowski Ran
Published: July 2015

Key Points

In Preprocedural CT, patients with BAV have larger aortic annulus perimeters, and more calcified valves compared with TAV.

In patients with BAV, self‐expandable valves were under‐expand and balloon‐expandable valves have a trend toward increased rates of postimplantation AR grade.

Self‐expandable valves have higher postprocedural gradient in BAV compared with TAV.
Nanomaterials, Autophagy, and Lupus Disease
Authors: Bianco Alberto , Muller Sylviane
Published: July 2015

Nanoscale materials hold great promise in the therapeutic field. In particular, as carriers or vectors, they help bioactive molecules reach their primary targets. Furthermore, by themselves, certain nanomaterials—regarded as protective—can modulate particular metabolic pathways that are deregulated in pathological situations. They can also synergistically improve the effects of a payload drug. These properties are the basis of their appeal. However, nanoscale materials can also have intrinsic properties that limit their use, and this is the case for certain types of nanomaterials that influence autophagy. This property can be beneficial in some pathological settings, but in others, if the autophagic flux is already accelerated, it can be deleterious. This is notably the case for systemic lupus erythematosus (SLE) and other chronic inflammatory diseases, including certain neurological diseases. The nanomaterial–autophagy interaction therefore must be treated with caution for therapeutic molecules and peptides that require vectorization for their administration.
A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease
Authors: Ji Bing , Genever Paul G. , Fagan Michael J.
Published: July 2015

Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma‐induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF‐β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti‐tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF‐β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF‐β inhibition in multiple myeloma‐induced bone disease. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.
An integrated mathematical model of the cardiovascular and respiratory systems
Authors: Trenhago Paulo Roberto , Fernandes Luciano Gonçalves , Müller Lucas Omar , Blanco Pablo Javier , Feijóo Raúl Antonino
Published: July 2015

This study presents a lumped model for the human cardiorespiratory system. Specifically, we incorporate a sophisticated gas dissociation and transport system to a fully integrated cardiovascular and pulmonary model. The model provides physiologically consistent predictions in terms of hemodynamic variables such as pressure, flow rate, gas partial pressures, and pH. We perform numerical simulations to evaluate the behavior of the partial pressures of oxygen and carbon dioxide in different vascular and pulmonary compartments. For this, we design the rest condition with low oxygen requirements and carbon dioxide production and exercise conditions with high oxygen demand and carbon dioxide production. Furthermore, model sensitivity to more relevant model parameters is studied. Copyright © 2015 John Wiley & Sons, Ltd.
A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies
Authors: de Vries Rob B. M. , Hooijmans Carlijn R. , Langendam Miranda W. , van Luijk Judith , Leenaars Marlies , Ritskes‐Hoitinga Merel , Wever Kimberley E.
Published: July 2015

Systematic reviews are an important method to support evidence‐based decisions in healthcare (research). Although not yet as common as clinical systematic reviews, the number of systematic reviews of animal studies has been increasing steadily in recent years. An important method to promote high‐quality systematic reviews is to pre‐specify the review methodology in a protocol, before the conduct of the systematic review itself. In contrast to clinical systematic reviews, a standard protocol format for systematic reviews of animal studies is not yet available. Here, we present a protocol format tailored to the preparation, registration and publication of systematic reviews of animal intervention studies (i.e. systematic reviews of animal experiments studying the efficacy and/or safety of interventions intended for use in human patients). In analogy to the Cochrane review protocol, the format helps authors predefine the methodological approach of their systematic review, from research question to data synthesis. We recommend that authors prospectively complete and agree on the protocol, and register and/or publish it to allow feedback on the proposed methodology and to avoid the introduction of bias during the review process. Opportunities for obtaining feedback, and for registration and publication of review protocols are also discussed.
Cardiac stem cell treatment in myocardial infarction: protocol for a systematic review and meta‐analysis of preclinical studies
Authors: Zwetsloot P. P. , Jansen of Lorkeers S. J. , Végh A. M. D. , van Hout G. P. J. , Currie G. L. , Goumans M. J. , Chamuleau S. A. J. , Sluijter J. P. G.
Published: July 2015

Cardiac‐derived stem or progenitor cells (CSCs) have emerged as a possible therapeutic intervention for myocardial infarction, potentially ameliorating the devastating effects caused by inadequate blood flow to the heart. The first human clinical trials using these myocardial‐derived cells have recently started, but scientific controversy exists regarding the efficacy and origin of some of these stem cells in preclinical animal models. Systematic review of the current literature on CSCs in ischaemic cardiomyopathy can provide useful additional information on the use of CSCs in preclinical trials. By combining all available data, we can adequately compare the different types of cells being used and possibly identify factors that influence cardiac stem cell therapy in general. This protocol provides a thorough description of the methodology that will be used in our systematic review and meta‐analysis of all preclinical animal studies involving cardiac stem cell treatment for ischaemic cardiomyopathy.
Optimal vegetation cover in the Horqin Sands, China
Authors: Mo Kangle , Cong Zhentao , Lei Huimin
Published: July 2015

Vegetation cover is an important index describing vegetation distribution, which is widely used to study vegetation dynamics. Eagleson presented an optimal vegetation cover hypothesis by the tradeoff of water supply and water demand based on strict mathematical and physical derivation. According to Eagleson's ecohydrological optimality, the positive correlation curve between canopy conductance and vegetation cover is obtained based on water demand; the negative correlation curve between canopy conductance and vegetation cover is obtained based on water supply. The optimal vegetation cover can be estimated by the cross point of these two curves. This method was applied in the Horqin Sands, China. Normalized difference vegetation index of Moderate Resolution Imaging Spectroradiometer dataset was used to calculate vegetation cover and the anthropological disturbance was excluded; meteorological data from three stations were used to estimate optimal vegetation cover. The vegetation cover by ecohydrological optimality (0.318) is consistent with the vegetation cover by remote sensing (0.317). The spatial map of optimal vegetation cover showed a more smooth transit in this area. Under this framework, the vegetation cover would decrease 17% with 10% precipitation decrease and it would decrease 16% with 10% air temperature decrease in this area. This method can be widely applied to determine the appropriate vegetation cover in vegetation restoration practice and to predict vegetation variation under climate change. Copyright © 2015 John Wiley & Sons, Ltd.
Insulin resistance in heart failure: differences between patients with reduced and preserved left ventricular ejection fraction
Authors: Scherbakov Nadja , Bauer Maximiliane , Sandek Anja , Szabó Tibor , Töpper Agnieszka , Jankowska Ewa A. , Springer Jochen , von Haehling Stephan , Anker Stefan D. , Lainscak Mitja , Engeli Stefan , Düngen Hans‐Dirk , Doehner Wolfram
Published: July 2015

Aims

Insulin resistance (IR) is a characteristic feature of heart failure (HF) pathophysiology that affects symptoms and mortality. Differences in the pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not characterized in detail. The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF.

Methods and results

We included 18 patients with HFrEF (EF 30 ± 11%, body mass index (BMI) 26.5 ± 3.3 kg/m2), 22 HFpEF patients (EF 63 ± 7%, BMI 28.6 ± 4.8 kg/m2), and 20 healthy controls of similar age, all without diabetes mellitus. Patients were in stable ambulatory condition and on stable medical regimens for HF. IR was assessed at fasting steady state by the homeostasis model assessment (HOMA) index and within the physiological range of insulin–glucose interactions by the short insulin sensitivity test (SIST). Fasting‐state IR was observed in HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range (IQR) 1.5–3.6 vs. HOMA 3.1, IQR 1.4–3.7 vs. controls 1.2, IQR 1.8–0.9, respectively; analysis of variance P < 0.001), but no statistical difference was observed between HFpEF and HFrEF. The dynamic test over the physiological range of insulin–glucose interactions revealed a more severe IR in HFrEF as compared with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64–89) mg/dL) at the end of the SIST compared with HFpEF and controls (68 (58–79) and 56 (44–66) mg/dL, respectively, P < 0.001).

Conclusion

IR is present in non‐diabetic patients with HFpEF and HFrEF. However, distinct differences in the insulin sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced testing. Patients with HFrEF showed more severe IR.
Geographic differences in heart failure trials
Authors: Ferreira João Pedro , Girerd Nicolas , Rossignol Patrick , Zannad Faiez
Published: July 2015

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial‐specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF‐PEF), heart failure with reduced ejection fraction (HF‐REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF‐PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity.
Verbal Versus Figural Fluency Tests in Currently Ill and Weight Restored Anorexia Nervosa Patients
Authors: Heled Eyal , Hoofien Dan , Bachar Eytan , Ebstein Richard P.
Published: July 2015

Fluency tests allow domain‐specific assessment of verbal and non‐verbal executive functions (EF) comparison and also enable utilizing of both quantitative and qualitative scoring methods. Thirty‐five currently ill anorexia nervosa patients (PANs), 33 weight‐restored patients (WRAN) and 47 healthy controls (HCs) were administered the word fluency test and the five‐point test. Results show that WRANs tended to perseverate more than HCs in the verbal‐fluency test. In addition, PANs produced significantly less correct figures and perseverated more than HCs and WRANs; HCs used more strategy methods than PANs and WRANs. Additionally, a positive correlation was found in the HC group between the total number of words in the verbal phonemic test and the number of designs produced and the number of correct designs. No such correlations were found in both anorexia groups. In conclusion, there is a differentiation between verbal and non‐verbal EF in PANs and WRANs, showing a deficiency in the non‐verbal domain. These findings may contribute to our understanding of the cognitive nature of the disorder. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
Sweet sorghum ideotypes: genetic improvement of the biofuel syndrome
Authors: Anami Sylvester Elikana , Zhang Li‐Min , Xia Yan , Zhang Yu‐Miao , Liu Zhi‐Quan , Jing Hai‐Chun
Published: July 2015

Compared to other potential feedstocks such as sugarcane, sugar beet, maize, and watermelon, sweet sorghum possesses higher levels of directly fermentable reducing sugars within the culm and the ability to accumulate high biomass under low‐input production systems. In addition, it is tolerant to drought and has more efficient utilization of solar radiation and nitrogen‐based fertilizers than maize and sugar cane on marginal lands that are not optimal for food production. These collectively make sweet sorghum to be considered with huge potential as a biofuel crop. Novel phenotypes generated during plant domestication and continued crop improvements via artificial selection constitute the domestication syndrome (Am. J. Bot., 101, 2014, 1711). Here, we draw an analogy and introduce the term the biofuel syndrome to refer to a suite of sweet sorghum traits, such as plant architecture (root, leave, and stem), flowering time and maturity as well as biomass bioconversion efficiency, that are associated with biofuel production and distinguish it from grain and forage sorghum traits. We discuss the biofuel syndrome amenable for targeted genetic modulation and what is currently known about the genetics and genomics of these traits as a potential route to optimize sweet sorghum for biofuel production. Continuous availability of sweet sorghum, transport and storing much mass and minimizing the postharvest loss of fermentable sugars are fundamental to exploiting sweet sorghum as a bioenergy crop. Due to the relatively short history of sweet sorghum breeding, we consider the development of ideotypes adapting to various phenological requirements to maximize the rapid deployment of sweet sorghum for biofuel production.
Alterations of the CD58 gene in classical Hodgkin lymphoma
Authors: Schneider Markus , Schneider Stefanie , Zühlke‐Jenisch Reina , Klapper Wolfram , Sundström Christer , Hartmann Sylvia , Hansmann Martin‐Leo , Siebert Reiner , Küppers Ralf , Giefing Maciej
Published: July 2015

Immune evasion plays a central role in the pathophysiology of classical Hodgkin lymphoma (cHL). As mutations of the CD58 gene contribute to immune evasion of diffuse large B cell lymphoma tumor cells, we studied whether alterations of the CD58 gene also occur in Hodgkin and Reed/Sternberg (HRS) cells of cHL. Single nucleotide polymorphism chip analysis revealed homozygous deletions within the CD58 gene in two cHL cell lines (SUP‐HD1 and U‐HO1). Sequencing of the CD58 gene in seven cHL cell lines disclosed in addition a homozygous splice site mutation in cell line KM‐H2. None of the three mutated lines expressed CD58 protein on their surface. Thus, three of seven cHL cell lines analyzed harbor destructive CD58 mutations. Molecular analysis of isolated HRS cells from 10 primary cases of cHL; however, did not reveal any case with a CD58 mutation. A FICTION study indicated heterozygous deletions of CD58 in 3 of 13 cHL analyzed. Overall, we report frequent inactivating mutations of CD58 in cHL cell lines, but their rare occurrence in primary HRS cells. As the three cHL cell lines with CD58 mutations were all established from HRS cells located in pleural effusions, i.e., outside the normal lymph node microenvironment, in end‐stages of the disease, CD58 inactivation in cHL might be predominantly prevalent to such situations. © 2015 Wiley Periodicals, Inc.
A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers
Authors: Kamada Yoshihiro , Ono Masafumi , Hyogo Hideyuki , Fujii Hideki , Sumida Yoshio , Mori Kojiroh , Tanaka Saiyu , Yamada Makoto , Akita Maaya , Mizutani Kayo , Fujii Hironobu , Yamamoto Akiko , Takamatsu Shinji , Yoshida Yuichi , Itoh Yoshito , Kawada Norifumi , Chayama Kazuaki , Saibara Toshiji , Takehara Tetsuo , Miyoshi Eiji
Published: July 2015

Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus, discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For the diagnosis of NASH, liver biopsy‐proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found that two glycobiomarkers, fucosylated haptoglobin (Fuc‐Hpt) and Mac‐2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc‐Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy‐proven NAFLD patients (training cohort). In addition, we found that the combination of serum Fuc‐Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic analyses, the area under the receiver operating characteristic curve, sensitivity, and specificity of the combination of these two glycobiomarkers were 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis using logistic regression analysis: logit (p) = −2.700 + 0.00242 × Fuc‐Hpt + 1.225 × Mac2bp. To validate the prediction model, another 382 biopsy‐proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the area under the receiver operating characteristic curve of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound‐diagnosed NAFLD subjects who received medical health checkups (n = 803). Our model also could predict NAFLD disease severity in this larger population. Conclusion: The combination of serum Fuc‐Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy. (Hepatology 2015;62:1433–1443)