bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyruvate cellular uptake and enzymatic conversion probed by dissolution DNP‐NMR: the impact of overexpressed membrane transporters
Authors: Balzan Riccardo , Fernandes Laetitia , Pidial Laetitia , Comment Arnaud , Tavitian Bertrand , Vasos Paul R.
Published: November 2016

Pyruvate membrane crossing and its lactate dehydrogenase‐mediated conversion to lactate in cells featuring different levels of expression of membrane monocarboxylate transporters (MCT4) were probed by dissolution dynamic nuclear polarization‐enhanced NMR. Hyperpolarized 13C‐1‐labeled pyruvate was transferred to suspensions of rodent tumor cell carcinoma, cell line 39. The pyruvate‐to‐lactate conversion rate monitored by dissolution dynamic nuclear polarization‐NMR in carcinoma cells featuring native MCT4 expression level was lower than the rate observed for cells in which the human MCT4 gene was overexpressed. The enzymatic activity of lactate dehydrogenase was also assessed in buffer solutions, following the real‐time pyruvate‐to‐lactate conversion speeds at different enzyme concentrations. Copyright © 2016 John Wiley & Sons, Ltd.
Chain‐by‐Chain Monte Carlo Simulation: A Novel Hybrid Method for Modeling Polymerization. Part I. Linear Controlled Radical Polymerization Systems
Authors: Demirel Özçam Derya , Teymour Fouad
Published: November 2016

Kinetic Monte Carlo (kMC) simulation is available for simulating microstructure of polymer chains with as much detail as one seeks at the expense of convergence tests and computational costs. A new hybrid deterministic–probabilistic method is developed as an alternative to kMC that builds chains one‐by‐one or chain‐by‐chain and it is named “Chain‐by‐Chain Monte Carlo” method (CBC‐MC). The CBC‐MC algorithm is tested on the synthesis of styrene/methyl methacrylate linear gradient copolymers via nitroxide‐mediated polymerization and methyl methacrylate/methyl acrylate linear hyperbolic gradient copolymers via atom transfer radical polymerization. Results are compared with kMC and method of moments and confirm that if applicable, full information regarding the microstructure of chains can be obtained using CBC‐MC method with reduced simulation times and smaller sample sizes.

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Understanding the continuum of radionecrosis and vascular disorders in the brain following gamma knife irradiation: An MRI study
Authors: Constanzo Julie , Masson‐Côté Laurence , Tremblay Luc , Fouquet Jérémie P. , Sarret Philippe , Geha Sameh , Whittingstall Kevin , Paquette Benoit , Lepage Martin
Published: November 2016

Purpose

The radiation dose delivered to brain tumors is limited by the possibility to induce vascular damage and necrosis in surrounding healthy tissue. In the present study, we assessed the ability of MRI to monitor the cascade of events occurring in the healthy rat brain after stereotactic radiosurgery, which could be used to optimize the radiation treatment planning.

Methods

The primary somatosensory forelimb area (S1FL) and the primary motor cortex in the right hemisphere of Fischer rats (n = 6) were irradiated with a single dose of Gamma Knife radiation (Leksell Perfexion, Elekta AG, Stockholm, Sweden). Rats were scanned with a small‐animal 7 Tesla MRI scanner before treatment and 16, 21, 54, 82, and 110 days following irradiation. At every imaging session, T2‐weighted (T2w), Gd‐DTPA dynamic contrast‐enhanced MRI (DCE‐MRI), and
‐weighted (
w) images were acquired to measure changes in fluid content, blood vessel permeability, and structure, respectively. At days 10, 110, and 140, histopathology was performed on brain sections. Locomotion and spatial memory ability were assessed longitudinally by behavioral tests.

Results

No vascular changes were initially observed. After 54 days, a small necrotic volume in the white matter below the S1FL, surrounded by an area presenting significant vascular permeability, was revealed. Between 54 and 110 days, the necrotic volume increased and was accompanied by the formation of a ring‐like region, where a mixture of necrosis and permeable blood vessels were observed, as confirmed by histology. Behavioral changes were only observed after day 82.

Conclusion

Together, DCE‐MRI and
w images supported by histology provided a coherent picture of the phenomena involved in the formation of new, leaky blood vessels, which was followed by the detection of radionecrosis in a preclinical model of brain irradiation. Magn Reson Med 78:1420–1431, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Unusual presentation Of Sjögren‐associated neuropathy with plasma cell‐rich infiltrate
Authors: Naddaf Elie , Berini Sarah E. , B. Dyck P. James , Laughlin Ruple S.
Published: November 2016

Introduction

Sjögren syndrome is thought to be a lymphocyte‐driven process. Peripheral nervous system involvement occurs in about 20%–25% of patients. A sensory‐predominant, large‐fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation.

Methods

We report a rare case of an acute Sjögren‐associated, sensory predominant, length‐dependent peripheral neuropathy mimicking Guillain–Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth.

Results

She had a positive Shirmer test, abnormal salivary gland scan, and positive SS‐A and SS‐B antibodies. A sural nerve biopsy showed an unusual, dense, non‐IgG4, polyclonal, plasma‐cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone.

Conclusions

Sjögren syndrome can present with acute‐onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605–608, 2017
Peripheral nerve ultrasound in cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS)
Authors: Pelosi Luciana , Leadbetter Ruth , Mulroy Eoin , Chancellor Andrew M. , Mossman Stuart , Roxburgh Richard
Published: November 2016

Introduction

We report preliminary findings of nerve ultrasound in patients with cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) who have sensory impairment due to dorsal root ganglionopathy.

Methods

The ultrasound cross‐sectional area (CSA) of median and ulnar nerves of 7 CANVAS patients was compared with 7 age‐ and gender‐matched controls and with the mean CSA of our reference population.

Results

The nerve CSA of CANVAS patients was significantly smaller than that of controls at all sites (P < 0.01). All but 1 individual measurement of CSA at the mid‐forearm level in the CANVAS patients fell outside the normal control range and was >2 standard deviations below the reference mean.

Conclusions

The small nerves in CANVAS probably reflect nerve thinning from axonal loss secondary to ganglion cell loss. Our data show a role for ultrasound in the diagnosis of CANVAS ganglionopathy. This may also be applicable to ganglionopathy from other causes. Muscle Nerve 56: 160–162, 2017.
Aggregation‐induced changes in the chemical exchange saturation transfer (CEST) signals of proteins
Authors: Goerke Steffen , Milde Katharina S. , Bukowiecki Raul , Kunz Patrick , Klika Karel D. , Wiglenda Thomas , Mogk Axel , Wanker Erich E. , Bukau Bernd , Ladd Mark E. , Bachert Peter , Zaiss Moritz
Published: November 2016

Chemical exchange saturation transfer (CEST) is an MRI technique that allows mapping of biomolecules (small metabolites, proteins) with nearly the sensitivity of conventional water proton MRI. In living organisms, several tissue‐specific CEST effects have been observed and successfully applied to diagnostic imaging. In these studies, particularly the signals of proteins showed a distinct correlation with pathological changes. However, as CEST effects depend on various properties that determine and affect the chemical exchange processes, the origins of the observed signal changes remain to be understood. In this study, protein aggregation was identified as an additional process that is encoded in the CEST signals of proteins. Investigation of distinct proteins that are involved in pathological disorders, namely amyloid beta and huntingtin, revealed a significant decrease of all protein CEST signals upon controlled aggregation. This finding is of particular interest with regard to diagnostic imaging of patients with neurodegenerative diseases that involve amyloidogenesis, such as Alzheimer's or Huntington's disease. To investigate whether the observed CEST signal decrease also occurs in heterogeneous mixtures of aggregated cellular proteins, and thus prospectively in tissue, heat‐shocked yeast cell lysates were employed. Additionally, investigation of different cell compartments verified the assignment of the protein CEST signals to the soluble part of the proteome. The results of in vitro experiments demonstrate that aggregation affects the CEST signals of proteins. This observation can enable hypotheses for CEST imaging as a non‐invasive diagnostic tool for monitoring pathological alterations of the proteome in vivo.
Addressing the Needs of Adults and Children with Disabilities through Emergency Preparedness and Organizational Improvisation
Authors: Fifolt Matthew , Wakelee Jessica , Eldridge‐Auffant Laurie , Carpenter Renae , Hites Lisle
Published: November 2016

The purpose of this qualitative study is to describe the experiences of fifteen organizational leaders and staff members who were responsible for caring for adults and children with disabilities during a 2014 winter storm. This study integrates the literature bases of emergency management and organizational improvisation. In response to this severe unexpected winter weather event, organizational leaders and staff members demonstrated creativity and flexibility in addressing the needs of clients, students, and patients, including adults and children with disabilities. The study concludes with reflections about emergency planning and organizational improvisation, practical implications, and a call to action to learn from these events and provide additional training and resources to individuals who may be in similar situations in the future.
The Caregiver Contribution to Heart Failure Self‐Care (CACHS): Further Psychometric Testing of a Novel Instrument
Authors: Buck Harleah G. , Harkness Karen , Ali Muhammad Usman , Carroll Sandra L. , Kryworuchko Jennifer , McGillion Michael
Published: November 2016

Caregivers (CGs) contribute important assistance with heart failure (HF) self‐care, including daily maintenance, symptom monitoring, and management. Until CGs’ contributions to self‐care can be quantified, it is impossible to characterize it, account for its impact on patient outcomes, or perform meaningful cost analyses. The purpose of this study was to conduct psychometric testing and item reduction on the recently developed 34‐item Caregiver Contribution to Heart Failure Self‐care (CACHS) instrument using classical and item response theory methods. Fifty CGs (mean age 63 years ±12.84; 70% female) recruited from a HF clinic completed the CACHS in 2014 and results evaluated using classical test theory and item response theory. Items would be deleted for low (<.05) or high (>.95) endorsement, low (<.3) or high (>.7) corrected item‐total correlations, significant pairwise correlation coefficients, floor or ceiling effects, relatively low latent trait and item information function levels (<1.5 and p > .5), and differential item functioning. After analysis, 14 items were excluded, resulting in a 20‐item instrument (self‐care maintenance eight items; monitoring seven items; and management five items). Most items demonstrated moderate to high discrimination (median 2.13, minimum .77, maximum 5.05), and appropriate item difficulty (−2.7 to 1.4). Internal consistency reliability was excellent (Cronbach α = .94, average inter‐item correlation = .41) with no ceiling effects. The newly developed 20‐item version of the CACHS is supported by rigorous instrument development and represents a novel instrument to measure CGs’ contribution to HF self‐care. © 2016 Wiley Periodicals, Inc.
Insulin resistance and its association with catch‐up growth in Chinese children born small for gestational age
Authors: Liu Chunhua , Wu Baiyan , Lin Niyang , Fang Xiaoyi
Published: November 2016

Objective

To assess insulin resistance and β‐cell function from birth to age 4 years and to examine their associations with catch‐up growth (CUG) in Chinese small‐for‐gestational‐age (SGA) children.

Methods

Weight and height were measured yearly from birth to age 4 years, and transformed into age‐ and gender‐adjusted SD scores. Fasting serum insulin and glucose were measured, and fasting insulin resistance and β‐cell function were estimated using the homeostasis model assessment (HOMA).

Results

The mean HOMA‐IR of the SGA group was significantly lower than that of the appropriate‐for‐gestational‐age (AGA) group at ages 2 and 3 years old, and the mean HOMA% of the SGA group was significantly lower than that of the AGA group at age 4 years old. At 4 years of age, HOMA for insulin resistance was positively correlated with the height gain and SD of height gain between 0 and 5 months, and HOMA% was positively correlated with the weight gain and SD of weight gain between 6 and 12 months in SGA children.

Conclusions

SGA children with CUG show a greater propensity to develop insulin resistance than AGA children between ages 2 and 4 years old. HOMA parameters are related to CUG in the first year of life.
Perceived weight status and weight change among a U.S. adult sample
Authors: Wang Monica L. , Haughton Christina F. , Frisard Christine , Pbert Lori , Geer Christine , Lemon Stephenie C.
Published: November 2016

Objective

Examine bidirectional associations between weight perception and weight change over time among adults.

Methods

Data are from adult employees (N = 623) across 12 U.S. public high schools participating in a cluster‐randomized multilevel weight gain prevention intervention. Data were collected at baseline, 12 months, and 24 months. Perceived weight status (very/somewhat underweight, just right, somewhat overweight, very overweight) were obtained via self‐administered surveys. Weight (kg) was measured by trained staff. Change in weight was calculated as the difference between baseline weight and weight at each follow‐up time point. Structural equation models were used to assess bidirectional associations of perceived weight status and change in weight over time. Models were adjusted for study condition, gender, age, race/ethnicity, education level, and previous time point.

Results

The sample was 65% female with a mean age of 44.6 (SD = 11.3). Nearly two thirds of the sample consisted of people with overweight (38.8%) or obesity (27.3%). Structural equation models indicated that baseline weight predicted subsequent perceived weight status (β = 0.26; P < 0.001), whereas baseline perceived weight status did not predict subsequent change in weight, adjusting for previous time point and covariates.

Conclusions

Results do not support bidirectional causality between weight perception and weight change in an adult sample.
Urinary Measurement of Epigenetic DNA Modifications: A Non‐Invasive Assessment of the Whole‐Body Epigenetic Status in Healthy Subjects and Colorectal Cancer Patients
Authors: Rozalski Rafal , Gackowski Daniel , Siomek‐Gorecka Agnieszka , Banaszkiewicz Zbigniew , Olinski Ryszard
Published: November 2016

Active mechanism of DNA demethylation can be responsible for the activation of previously silenced genes. Products of 5‐methylcytosine oxidation are released into the bloodstream and eventually excreted with urine. Therefore, whole‐body epigenetic status can be assessed non‐invasively on the basis of the urinary excretion of a broad spectrum of epigenetic modifications: 5‐hydroxymethylcytosine (5‐hmCyt), 5‐formylcytosine (5‐fCyt), 5‐carboxycytosine (5‐caCyt), and 5‐hydroxymethyluracil (5‐hmUra). We have developed a specific and sensitive, isotope‐dilution, automated, online, two‐dimensional ultra‐performance liquid chromatography system with tandem mass spectrometry (2D UPLC–MS/MS) to measure 5‐hmCyt, 5‐fCyt, 5‐caCyt, and their deoxynucleosides in the same urine sample. Human urine contains all of the modifications except from 5‐formyl‐2′‐deoxycytidine (5‐fdC) and 5‐carboxy‐2′‐deoxycytidine (5‐cadC). A highly significant difference in the urinary excretion of 5‐(hydroxymethyl)‐2’‐deoxycytidine (5‐hmdC) was found between healthy subjects and colorectal cancer patients (3.5 vs. 7.8 nmol mmol−1 creatinine, respectively), as well as strong correlations between the majority of analyzed compounds.
Validation of risk stratification for children with febrile neutropenia in a pediatric oncology unit in India
Authors: Das Anirban , Trehan Amita , Oberoi Sapna , Bansal Deepak
Published: November 2016

Purpose

The study aims to validate a score predicting risk of complications in pediatric patients with chemotherapy‐related febrile neutropenia (FN) and evaluate the performance of previously published models for risk stratification.

Patients and Methods

Children diagnosed with cancer and presenting with FN were evaluated in a prospective single‐center study. A score predicting the risk of complications, previously derived in the unit, was validated on a prospective cohort. Performance of six predictive models published from geographically distinct settings was assessed on the same cohort.

Results

Complications were observed in 109 (26.3%) of 414 episodes of FN over 15 months. A risk score based on undernutrition (two points), time from last chemotherapy (<7 days = two points), presence of a nonupper respiratory focus of infection (two points), C‐reactive protein (>60 mg/l = five points), and absolute neutrophil count (<100 per μl = two points) was used to stratify patients into “low risk” (score <7, n = 208) and assessed using the following parameters: overall performance (Nagelkerke R2 = 34.4%), calibration (calibration slope = 0.39; P = 0.25 in Hosmer–Lemeshow test), discrimination (c‐statistic = 0.81), overall sensitivity (86%), negative predictive value (93%), and clinical net benefit (0.43). Six previously published rules demonstrated inferior performance in this cohort.

Conclusion

An indigenous decision rule using five simple predefined variables was successful in identifying children at risk for complications. Prediction models derived in developed nations may not be appropriate for low‐middle‐income settings and need to be validated before use.
Late outcomes of adult survivors of childhood non‐Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study
Authors: Ehrhardt Matthew J. , Sandlund John T. , Zhang Nan , Liu Wei , Ness Kirsten K. , Bhakta Nickhill , Chemaitilly Wassim , Krull Kevin R. , Brinkman Tara M. , Crom Deborah B. , Kun Larry , Kaste Sue C. , Armstrong Gregory T. , Green Daniel M. , Srivastava Kumar , Robison Leslie L. , Hudson Melissa M. , Mulrooney Daniel A.
Published: November 2016

Background

Survivors of childhood non‐Hodgkin lymphoma (NHL) are at increased risk for chronic health conditions. The objective of this study was to characterize health conditions, neurocognitive function, and physical performance among a clinically evaluated cohort of 200 childhood NHL survivors.

Method

Chronic health and neurocognitive conditions were graded as per a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and impaired physical function defined as performance < 10th percentile of normative data. Multivariable regression was used to investigate associations between sociodemographic characteristics, therapeutic exposures, and outcomes.

Results

Survivors were a median age of 10 years (range 1–19) at diagnosis and 34 years (range 20–58) at evaluation. Eighty‐eight (44%) received radiation, 46 (23%) cranial radiation, and 69 (35%) high‐dose methotrexate. Most prevalent CTCAE Grades 3–4 (severe life‐threatening) conditions were obesity (35%), hypertension (9%), and impairment of executive function (13%), attention (9%), and memory (4%). Many had impaired strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%). Demographic and treatment‐related factors were associated with the development of individual chronic diseases and functional deficits.

Conclusions

Clinical evaluation identified a high prevalence of chronic health conditions, neurocognitive deficits, and performance limitations in childhood NHL survivors.
Lupus anticoagulant hypoprothrombinemia syndrome associated with severe thrombocytopenia in a child
Authors: Foord Aimee , Baca Nicole , Buchbinder David , Mahajerin Arash
Published: November 2016

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) comprises lupus anticoagulant, acquired hypoprothrombinemia, and often mild thrombocytopenia or normal platelets. It is usually associated with autoimmunity or postviral illness. We describe a case of a 10‐year‐old boy with oral bleeding and severe thrombocytopenia initially suggestive of immune thrombocytopenia. Secondary to bleeding, evaluation demonstrated prolonged coagulation tests and subsequently revealed the presence of lupus anticoagulant and hypoprothrombinemia, along with marked autoimmunity, suggestive of LAHPS. He was treated with intravenous immunoglobulin and hydroxychloroquine. This case report and discussion highlight the diagnostic and therapeutic challenges associated with LAHPS and coincident severe thrombocytopenia.
Detailed dynamic mechanical analysis of thermomechanically stable melt‐processed PEK–MWCNT nanocomposites
Authors: Chauhan Sampat Singh , Singh Bhanu P. , Malik Rajender Singh , Verma Pawan , Choudhary Veena
Published: November 2016

This article reports the detailed study of dynamic mechanical properties of multiwalled carbon nanotubes/poly(ether ketone) nanocomposites prepared by melt blending. The dynamic mechanical characterisitic parameters such as storage modulus (E′), loss modulus (E″) and damping factor (tan δ) were explored in detail to investigate the adhesion factor (A), strength factor (B), efficiency factor (C), and entanglement density (N). Adhesion factor, which is inversely related to the degree of interaction between nanotubes and matrix, decreased with increase in MWCNT loading. Strength factor (B) which is a direct measure of interaction between MWCNTs and PEK increased with increase in MWCNT loading. The effect of nanotubes on moduli of composites is calculated in terms of coefficient of reinforcement (C factor). Lower is the value of coefficient (C) higher will be the effectiveness of reinforcement on moduli of composites. It decreased from value of 1 at 1 wt% MWCNTs loading in PEK to 0.67 at 5 wt% MWCNTs loading which point towards increased effectiveness of MWCNTs at 5 wt% loading for excellent properties. To compliment these findings, entanglement density (N) was also calculated. Furthermore, Cole–Cole analysis was carried out to demonstrate the compatibility of both the components in composite system. POLYM. COMPOS., 39:2587–2596, 2018. © 2016 Society of Plastics Engineers
Characterization of wood plastic composite based on HDPE and cashew nutshells processed in a thermokinetic mixer
Authors: Gomes Victor N.C. , Carvalho Amanda G. , Furukava Marciano , Medeiros Eliton S. , Colombo Ciliana R. , Melo Tomás J.A. , Araújo Edcleide M. , Morais Dayanne D.S. , Ueki Marcelo M. , Paskocimas Carlos A. , Santos Amélia S.F.
Published: November 2016

Wood plastic composites (WPC), which are used in high‐value markets, contribute to solve some of the problems associated with municipal solid waste accumulation. In this study, the effect of cashew nutshell powder (CNSP) content on properties of formulations with recycled high‐density polyethylene, 5 wt% of maleic anhydride grafted polypropylene and 5 wt% of struktol TPW 113, a blend of complex, modified fatty acid ester, was evaluated. Mixtures containing from 20 to 60 wt% CNSP were melt‐processed, using a thermokinetic mixer. WPC's were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and melt flow index (MFI) measurements. Composite morphology and mechanical properties were also accessed, respectively, by scanning electron microscopy and tensile tests. Results show that the tensile strength of composites decreased as the content of CNSP increased due to poor reinforcement–matrix interface and voids formed during residual cashew nutshell liquid (CNSL) vaporization. On the other hand, elastic modulus decreased and elongation at break increased, both indicating a plasticizing effect of the residual CNSL, confirmed by crystallinity and MFI data. Differences in the thermal stability of composites were restricted to thermal behavior of main components. POLYM. COMPOS., 39:2662–2673, 2018. © 2016 Society of Plastics Engineers
Investigation of relationship between crystallization kinetics and interfacial interactions in plasticized poly(lactic acid)/POSS nanocomposites: “Effects of different POSS types”
Authors: Kodal Mehmet , Sirin Humeyra , Ozkoc Guralp
Published: November 2016

In this study, the correlation between crystallization behavior and interfacial chemistry of polyhedral oligomeric silsesquioxane (POSS)/poly(ethylene glycol) (PEG)‐plasticized poly(lactic acid) (PLA) nanocomposites was investigated. Four different kinds of POSS particles having different chemical structures were used. The nanocomposites were melt compounded in a twin‐screw microcompounder. Nonisothermal crystallization behavior of PLA/PEG/POSS nanocomposites was evaluated from common kinetic models such as Avrami, Avrami‐Ozawa, and Kissinger. Besides, nucleating activity of the POSS particles was investigated in terms of Dobreva and Gutzow models. It was found that crystallization rate of PLA enhanced in the presence of POSS particles. Ozawa model was failed to describe the nonisothermal crystallization behavior of PLA/PEG/POSS nanocomposites. POSS particles introduced into the PLA/PEG matrix took the role of effective nucleating agents during crystallization. Activation energies of crystallization were evaluated by Kissinger and Takhor method. Polarized optical microscopy analysis showed that the spherulite nucleation density of PLA/PEG/POSS nanocomposites was much higher than that of the neat PLA. In order to investigate the interfacial interactions between POSS particles and plasticized PLA, thermodynamic work of adhesion approach was adopted using the experimentally determined surface energies. A strong correlation was obtained between interfacial chemistry and the nucleation rate in plasticized PLA/POSS nanocomposites. It was found that polar interactions were the dominating factor, which determines the nucleation activity of the POSS particles. POLYM. COMPOS., 39:2674–2684, 2018. © 2016 Society of Plastics Engineers
Views of American OB/GYNs on the ethics of prenatal whole‐genome sequencing
Authors: Bayefsky Michelle J. , White Amina , Wakim Paul , Hull Sara Chandros , Wasserman David , Chen Stephanie , Berkman Benjamin E.
Published: November 2016

Objective

Given public demand for genetic information, the potential to perform prenatal whole‐genome sequencing (PWGS) non‐invasively in the future, and decreasing costs of whole‐genome sequencing, it is likely that OB/GYN practice will include PWGS. The goal of this project was to explore OB/GYNs' views on the ethical issues surrounding PWGS and their preparedness for counseling patients on its use.

Methods

A national survey was administered to 2500 members of American Congress of Obstetricians and Gynecologists.

Results

A total of 1114 respondents completed the survey (response rate = 45%). OB/GYNs are most concerned with ordering non‐medical fetal genetic information, are worried about increasing parental anxiety, and feel it is appropriate to be directive when counseling parents about PWGS. Furthermore, most OB/GYNs have limited knowledge of genetics, rely heavily on genetic counselors and would like more guidance regarding the clinical adoption of PWGS.

Conclusion

OB/GYNs do not completely accept or reject PWGS, but a substantial number have significant ethical and practical concerns. They are most concerned with issues that will directly affect their practices and interactions with patients, such as increasing parental anxiety and costs of care. Professional guidance would be instrumental in directing the adoption of PWGS and alleviating the ethical burden posed by PWGS on individual OB/GYNs. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Intra‐ and inter‐observer reproducibility and generalizability of first trimester uterine artery pulsatility index by transabdominal and transvaginal ultrasound
Authors: Marchi Laura , Zwertbroek Eva , Snelder Judith , Kloosterman Maaike , Bilardo Caterina Maddalena
Published: November 2016

Objectives

The primary aim of the study was to assess intra‐observer and inter‐observer reproducibility and generalizability (general reliability) of first trimester Doppler measurements of uterine arteries (UtA) performed both transabdominally (TA) and transvaginally (TV). Secondary aims were to investigate whether maternal BMI and acquisition modality (transabdominal or transvaginal) affect feasibility and reliability of UtA Doppler evaluation.

Methods

Singleton pregnancies between 11+0 and 13+6 weeks underwent TA and TV Doppler measurements of UtA prospectively, blindly and independently by Fetal Medicine Foundation‐accredited operators. The more experienced operator performed all the scans to assess intra‐observer reproducibility. Inter‐observer reproducibility and generalizability was evaluated among different operators and different ultrasound equipment. Intra‐ and inter‐rater reliability was assessed by Concordance Correlation Coefficient and Intraclass Correlation Coefficient; agreement was estimated with Limits of Agreement and reported graphically with Bland–Altman plots. Correlation between BMI and feasibility and accuracy of UtA measurements were studied with Spearman's correlation coefficient. Differences between TA and TV measurements were evaluated by Wilcoxon test.

Results

A total of 101 women were enrolled. The intra‐observer reproducibility for TA and TV measurements ranged from 0.87 to 0.94, respectively. The inter‐observer reproducibility varied from 0.57 (for TA measurements by the less experienced operator) to 0.95 (for TV measurements by the more experienced operator), and it was independent of the ultrasound equipment used. Spearman's correlation coefficient failed to demonstrate a correlation between BMI and time to get the first set of TA–TV measurements, or between BMI and TA–TV reproducibility. In four patients, the operators could not obtain the TA measurements due to high BMI. In our population the UtA pulsatility index (PI) values did not differ significantly between the TA or TV approach.

Conclusions

UtA PI measurements obtained by experienced operators show a moderate intra‐ and inter‐observer reproducibility. The TV approach might be used when TA measurements fail in obese women, especially since specific reference ranges for TV measurements may not be necessary. © 2016 John Wiley & Sons, Ltd.
Nicotine‐induced protein expression profiling reveals mutually altered proteins across four human cell lines
Authors: Paulo Joao A. , Gygi Steven P.
Published: November 2016

Mass spectrometry‐based proteomic strategies can profile the expression level of proteins in response to external stimuli. Nicotine affects diverse cellular pathways, however, the nicotine‐induced alterations on the global proteome across human cell lines have not been fully elucidated. We measured perturbations in protein levels resulting from nicotine treatment in four cell lines—HEK, HeLa, PaSC, and SH‐SY5Y—in a single experiment using tandem mass tags (TMT10‐plex) and high‐resolution mass spectrometry. We quantified 8590 proteins across all cell lines. Of these, nicotine increased the abundance of 31 proteins 1.5‐fold or greater in all cell lines. Likewise, considering proteins with altered levels in at least three of the four cell lines, 64 were up‐regulated, while one was down‐regulated. Gene ontology analysis revealed that ∼40% of these proteins were membrane bound, and functioned in transmembrane signaling and receptor activity. We highlighted proteins, including APP, APLP2, LAPTM4B, and NCOA4, which were dysregulated by nicotine in all cell lines investigated and may have implications in downstream signaling pathways, particularly autophagy. Using the outlined methodology, studies in additional (including primary) cell lines will provide further evidence that alterations in the levels of these proteins are indeed a general response to nicotine and thereby merit further investigation.
A robotic protocol for high‐throughput processing of samples for selected reaction monitoring assays
Authors: Zhu Min , Zhang Pingbo , Geng‐Spyropoulos Minghui , Moaddel Ruin , Semba Richard D. , Ferrucci Luigi
Published: November 2016

Selected reaction monitoring mass spectrometry (SRM‐MS) is a sensitive and accurate method for the quantification of targeted proteins in biological specimens. However, the sample throughput and reliability of this technique is limited by the complexity of sample preparation, as well as instrumentation and data processing. Modern robotic equipment allows for rapid and accurate processing of large number of samples and makes SRM‐MS assay applicable in epidemiological studies. Herein, we describe an automated sample processing platform developed in the context of an SRM‐MS protocol for the assay of complement factor H protein and its variants in human plasma. We report detailed performance data on plasma digestion, sample cleanup and optimized robotic handling implemented on a Biomek® NXp Workstation. Method validation was assessed with isotopically labeled peptide standards and had high reproducibility of intra‐day assay (CVs from 2.7 to 17.5% with median CV of 5.3%) and inter‐day assay (CVs from 4.8 to 17.6 with median CV of 7.2%) for all peptides.
Purification of soluble HLA class I complexes from human serum or plasma deliver high quality immuno peptidomes required for biomarker discovery
Authors: Ritz Danilo , Gloger Andreas , Neri Dario , Fugmann Tim
Published: November 2016

Soluble human leukocyte antigen class I (sHLA)‐peptide complexes have been suggested to play a role in the modulation of immune responses and in immune evasion of cancer cells. The set of peptides eluted from sHLA molecules could serve as biomarker for the monitoring of patients with cancer or other conditions. Here, we describe an improved sHLA peptidomics methodology resulting in the identification of 1816 to 2761 unique peptide sequences from triplicate analyses of serum or plasma taken from three healthy donors. More than 90% of the identified peptides were 8–11mers and 74% of these sequences were predicted to bind to cognate HLA alleles, confirming the quality of the resulting immunopeptidomes. In comparison to the HLA peptidome of cultured cells, the plasma‐derived peptides were predicted to have a higher stability in complex with the cognate HLA molecules and mainly derived from proteins of the plasma membrane or from the extracellular space. The sHLA peptidomes can efficiently be characterized by using the new methodology, thus serving as potential source of biomarkers in various pathological conditions.
Pro‐ and anti‐inflammatory cytokine associations with major depression in cancer patients
Authors: Li Madeline , Kouzmina Ekaterina , McCusker Megan , Rodin Danielle , Boutros Paul C. , Paige Christopher J. , Rodin Gary
Published: November 2016

Objective

Cytokines may be linked to depression, although it has been challenging to demonstrate this association in cancer because of the overlap between depressive symptoms and other sickness behaviors. This study investigates the relationship between cytokines and depression in cancer patients, accounting for confounding clinical and methodological factors.

Methods

The GRID Hamilton Rating Scale for Depression and Neurotoxicity Rating Scale (NRS) for cytokine‐induced sickness behaviors were administered to 61 cancer patients and 38 healthy controls. The cancer group was of mixed type and largely of late stage, with a recruitment rate of 35% and completion rate of 47%. Major depression was diagnosed in 19 of 61 (31%) cancer patients. Multiplexed cytokine assays for inflammatory and anti‐inflammatory cytokines were conducted in plasma samples using electrochemiluminescence.

Results

All cancer patients had high NRS scores and elevated levels of most cytokines. Cancer patients with major depression had higher NRS scores than those without major depression. IL‐1rα was positively associated with the GRID scores of depressive symptoms (regression coefficient, 3.52 ± 1.18; P = .004), but not with major depression. Major depression was negatively associated with the anti‐inflammatory cytokine IL‐4 (regression coefficient, −0.65 ± 0.26; P = .013), but not with IL‐1rα.

Conclusions

Depressive symptoms in cancer patients may represent sickness behaviors, which may have distinct cytokine associations from major depression. Sickness behaviors may be associated with an increase in inflammatory cytokines, whereas major depression may be induced by a failure to adequately resolve inflammation. Our findings suggest that cytokine‐mediated interventions may be of value to treat depression in this population.
Energetics of reactions in a dielectric barrier discharge with argon carrier gas: V hydrocarbons
Authors: Nisol Bernard , Watson Sean , Lerouge Sophie , Wertheimer Michael R.
Published: November 2016

We report dielectric barrier discharge (DBD)‐based atmospheric pressure (AP) plasma polymerization (PP) experiments using argon carrier gas and a wide variety of hydrocarbon molecules as the precursors (“monomers”). As in our preceding research with other reagents, unprecedented precision and reproducibility in energy measurements is again demonstrated. Measurements based on various aliphatic and aromatic hydrocarbon compounds have yielded values of Em, the energy absorbed from the plasma by each monomer molecule. Systematic differences among families of compounds enabled us to draw several important conclusions about fragmentation and polymerization in the DBD plasma environment, observations which are in fair qualitative agreement with low‐pressure radio‐frequency PP data by Yasuda and Hirotsu from the 1970s.
An automated method to evaluate the enzyme kinetics of β‐glucosidases
Authors: Klimeš Pavel , Mazura Pavel , Turek Dušan , Brzobohatý Břetislav
Published: November 2016

Enzyme kinetic measurements are important for the characterization and engineering of biocatalysts, with applications in a wide range of research fields. The measurement of initial reaction velocity is usually slow and laborious, which motivated us to explore the possibilities for automating this process. Our model enzyme is the maize β‐glucosidase Zm‐p60.1. Zm‐p60.1 plays a significant role in plant growth and development by regulating levels of the active plant hormone cytokinin. Zm‐p60.1 belongs to a wide group of hydrolytic enzymes. Members of this group hydrolyze several different types of glucosides, releasing glucose as a secondary product. Enzyme kinetic measurements using artificial substrates are well established, but burdensome and time‐consuming. Thus, they are a suitable target for process automation. Simple optical methods for enzyme kinetic measurements using natural substrates are often impossible given the optical properties of the enzymatic reaction products. However, we have developed an automated method based on glucose detection, as glucose is released from all substrates of glucosidase reactions. The presented method can obtain 24 data points from up to 15 substrate concentrations to precisely describe the enzyme kinetics. The combination of an automated liquid handling process with assays that have been optimized for measuring the initial hydrolysis velocity of β‐glucosidases yields two distinct methods that are faster, cheaper, and more accurate than the established protocols.
Thermodynamic deficiencies of some simple Lindblad operators
Authors: Stockburger Jürgen T. , Motz Thomas
Published: November 2016

Master equations of Lindblad type have attained prominent status in the fields of quantum optics and quantum information since they are guaranteed to satisfy fundamental notions of quantum dynamics such as complete positivity. When Lindblad operators are used to describe thermal reservoirs in contact with an open quantum system, the fundamental laws of thermodynamics and the fluctuation‐dissipation theorem provide additional mandatory criteria. We show several examples of innocent‐looking Lindblad operators which have questionable properties in this regard. Compatibility criteria between Hamiltonian and Lindblad terms as well as consequences of their violation are discussed. An alternative stochastic approach to dissipative quantum dynamics is outlined and illustrated through a harmonic‐chain model for which the approach of local Lindblad operators fails.
The NMR solution structure and function of RPA3313: a putative ribosomal transport protein from Rhodopseudomonas palustris
Authors: Catazaro Jonathan , Lowe Austin J. , Cerny Ronald L. , Powers Robert
Published: November 2016

Protein function elucidation often relies heavily on amino acid sequence analysis and other bioinformatics approaches. The reliance is extended to structure homology modeling for ligand docking and protein–protein interaction mapping. However, sequence analysis of RPA3313 exposes a large, unannotated class of hypothetical proteins mostly from the Rhizobiales order. In the absence of sequence and structure information, further functional elucidation of this class of proteins has been significantly hindered. A high quality NMR structure of RPA3313 reveals that the protein forms a novel split ββαβ fold with a conserved ligand binding pocket between the first β‐strand and the N‐terminus of the α‐helix. Conserved residue analysis and protein–protein interaction prediction analyses reveal multiple protein binding sites and conserved functional residues. Results of a mass spectrometry proteomic analysis strongly point toward interaction with the ribosome and its subunits. The combined structural and proteomic analyses suggest that RPA3313 by itself or in a larger complex may assist in the transportation of substrates to or from the ribosome for further processing. Proteins 2016; 85:93–102. © 2016 Wiley Periodicals, Inc.
Predicting protein conformational changes for unbound and homology docking: learning from intrinsic and induced flexibility
Authors: Chen Haoran , Sun Yuanfei , Shen Yang
Published: November 2016

Predicting protein conformational changes from unbound structures or even homology models to bound structures remains a critical challenge for protein docking. Here we present a study directly addressing the challenge by reducing the dimensionality and narrowing the range of the corresponding conformational space. The study builds on cNMA—our new framework of partner‐ and contact‐specific normal mode analysis that exploits encounter complexes and considers both intrinsic and induced flexibility. First, we established over a CAPRI (Critical Assessment of PRedicted Interactions) target set that the direction of conformational changes from unbound structures and homology models can be reproduced to a great extent by a small set of cNMA modes. In particular, homology‐to‐bound interface root‐mean‐square deviation (iRMSD) can be reduced by 40% on average with the slowest 30 modes. Second, we developed novel and interpretable features from cNMA and used various machine learning approaches to predict the extent of conformational changes. The models learned from a set of unbound‐to‐bound conformational changes could predict the actual extent of iRMSD with errors around 0.6 Å for unbound proteins in a held‐out benchmark subset, around 0.8 Å for unbound proteins in the CAPRI set, and around 1 Å even for homology models in the CAPRI set. Our results shed new insights into origins of conformational differences between homology models and bound structures and provide new support for the low‐dimensionality of conformational adjustment during protein associations. The results also provide new tools for ensemble generation and conformational sampling in unbound and homology docking. Proteins 2017; 85:544–556. © 2016 Wiley Periodicals, Inc.
Gadolinium containing telechelic PEG‐polymers end‐capped by di‐phenylalanine motives as potential supramolecular MRI contrast agents
Authors: Diaferia Carlo , Gianolio Eliana , Accardo Antonella , Morelli Giancarlo
Published: November 2016

Telechelic PEG‐polymers end‐capped by diphenylalanine (FF) motives and containing a DOTA‐Gd complex, bound on a lysine side chain at the centre of peptide moiety, are studied for their assembling properties and for the relaxometric behavior. The observed variations in terms of relaxivity are correlated to the assembling properties of the aggregates by using several techniques: fluorescence, Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) for aggregation tendency and secondary structure determination; Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) for morphological definition. Self‐aggregation in water solution of the peptide conjugates, due to interaction of the phenylalanine frameworks, starts at concentration around 1 mg/ml with a first evidence of the coexistence of fibrillary networks and hydrogels at 10 mg/ml. Definitive presence of well‐structured fibrillary networks, dominated by an antiparallel β‐sheet arrangement, occurs at 50 mg/ml. At the latter concentration relaxivity values measured at 20 MHz and 298 K, are around 11 mM−1 s−1, in line with a possible use of the these aggregates as MRI contrast agents. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Effects of polysilane‐doped spiro‐OMeTAD hole transport layers on photovoltaic properties
Authors: Shirahata Yasuhiro , Yamomoto Yuki , Suzuki Atsushi , Oku Takeo , Fukunishi Sakiko , Kohno Kazufumi
Published: November 2016

Effects of polysilane‐doped 2,2′,7,7′‐tetrakis‐(N,N‐di‐p‐methoxyphenylamino)‐9,9′‐spirobifluorene (spiro‐OMeTAD) hole transport layers on photovoltaic properties were investigated by measuring current density–voltage characteristics and incident photon‐to‐current conversion efficiency of CH3NH3PbI3‐based photovoltaic devices. Three kinds of polysilanes were used as the dopants. Due to the polysilane doping, conversion efficiencies of the CH3NH3PbI3 devices using the polysilane‐doped hole transport layers were improved. Microstructures of the CH3NH3PbI3 devices were also investigated. Based on the results of the microstructure analysis, impact of silicon in the polysilanes doped into spiro‐OMeTAD layer on photovoltaic properties were discussed.
The impact of interface and border traps on current–voltage, capacitance–voltage, and split‐CV mobility measurements in InGaAs MOSFETs
Authors: Pavan Paolo , Zagni Nicolò , Puglisi Francesco Maria , Alian Alireza , Thean Aaron Voon‐Yew , Collaert Nadine , Verzellesi Giovanni
Published: November 2016

In this article, we present coupled experimental/simulated results about the influence of interface and border traps on the electrical characteristics and split‐CV mobility extraction in InGaAs MOSFETs. These results show that border traps limit the maximum drain current under on‐state conditions, induce a hysteresis in the quasi‐static transfer characteristics, as well as affect CV measurements, inducing an increase in the accumulation capacitance even at high frequencies where trap effects are commonly assumed to be negligible. Hysteresis in the transfer characteristics can be used as a sensitive monitor of border traps, as suggested by a sensitivity analysis where either the energetic or the spatial distribution of border traps are varied. Finally, we show that mobility extraction by means of the split‐CV method is affected by appreciable errors related to the spurious contributions of interface and border traps to the total gate charge, ultimately resulting in significant channel mobility underestimation. In very narrow channel devices, channel electron spilling over the InP buffer layer can also contribute to mobility measurement inaccuracy.