bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative monocyte‐to‐lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors
Authors: Cananzi Ferdinando Carlo Maria , Minerva Eleonora Maddalena , Samà Laura , Ruspi Laura , Sicoli Federico , Conti Lorenzo , Fumagalli Romario Uberto , Quagliuolo Vittorio Lorenzo
Published: November 2018

Background and Objectives

Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining gastrointestinal stromal tumors (GISTs) outcome.

Methods

Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil‐lymphocyte ratio (NLR), monocyte‐lymphocyte ratio (MLR), platelet‐lymphocyte ratio (PLR), neutrophil‐white blood cell ratio (NWR), lymphocyte‐white cell ratio (LWR), monocyte‐white cell ratio (MWR), and platelet‐white cell ratio (PWR).

Results

We analyzed 127 patients. Three‐ and five‐year disease‐free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location (
P = 0.024), cell type (
P = 0.024), mitosis (
P < 0.001), MLR (
P = 0.014), NLR (
P = 0.016), and PLR (
P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis (
P = 0.001), NLR (
P = 0.015), MLR (
P = 0.015), and PLR (
P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinen's risk class. A high value of MLR was associated with reduced DFS.

Conclusion

MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs. We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.
Pressure drop in liquid chromatography
Authors: Podgornik Aleš
Published: November 2018

Measurement of pressure drop is routinely performed during chromatographic runs. In many cases this information is only used for regulation of mobile phase flow rate to keep pressure drop below defined limit. However, pressure drop can provide additional important information about performance of chromatographic process. In this review different parameters affecting pressure drop such as compressibility of chromatographic media, nature of applied sample and mobile phase flow regime are discussed. Detailed analysis correlating organization of particle based chromatographic media and pressure drop is presented together with its extension to convective media such as membranes and monoliths but also novel 3D printed media. Finally, estimation of layer thickness formed by adsorbed molecules based on a pressure drop data is presented and its applicability is discussed.
Understanding Gender Differences in Resilience Among Veterans: Trauma History and Social Ecology
Authors: Portnoy Galina A. , Relyea Mark R. , Decker Suzanne , Shamaskin‐Garroway Andrea , Driscoll Mary , Brandt Cynthia A. , Haskell Sally G.
Published: November 2018

A social‐ecological framework for resilience underscores the importance of conceptualizing individuals embedded within their context when evaluating a person's vulnerability and adaptation to stress. Despite a high level of trauma exposure, most veterans exhibit psychological resilience following a traumatic event. Interpersonal trauma is associated with poorer psychological outcomes than noninterpersonal trauma and is experienced more frequently across the lifespan by women as compared to men. In the present study, we examined gender differences in trauma exposure, resilience, and protective factors among veterans. Participants included 665 veterans who completed a baseline survey assessing traumatic events; 544 veterans (81.8%) completed a 1‐year follow‐up survey assessing resilience, combat exposure, deployment social support, deployment preparedness, and military sexual trauma (MST). Principal component analyses revealed the Traumatic Life Events Questionnaire categorized into four meaningful components: sexual abuse, interpersonal violence, stranger violence, and accidents/unexpected trauma. Women reported greater exposure to sexual abuse, d = 0.76; interpersonal violence, d = 0.31; and MST, Cramer's V = 0.54; men reported greater exposure to stranger violence, accidents/unexpected trauma, and combat exposure, ds = 0.24–0.55. Compared to women, men also reported greater social support during deployment, d = 0.46. Hierarchical linear regression indicated that men's resilience scores were higher than women's, β = .10, p = .032, yet this association was no longer significant once we accounted for trauma type, β = .07, p = .197. Results indicate that trauma type is central to resilience and suggest one must consider the social‐ecological context that can promote or inhibit resilient processes.
Characterization of Breast Microcalcifications Using a New Ultrasound Image‐Processing Technique
Authors: Machado Priscilla , Eisenbrey John R. , Stanczak Maria , Cavanaugh Barbara C. , Zorn Lisa M. , Forsberg Flemming
Published: November 2018

Objectives

To evaluate a new commercial image‐processing technique (MicroPure; Toshiba America Medical Systems, Tustin, CA) for detection and characterization of breast microcalcifications in patients undergoing stereotactic or ultrasound‐guided biopsies using mammography as the reference standard.

Methods

One hundred female patients, with a total of 104 lesions, scheduled for an image‐guided biopsy of an area with breast microcalcifications (identified on a prior mammogram) underwent MicroPure examinations of the breast using an Aplio XG scanner (Toshiba America Medical Systems) with a broad‐bandwidth linear array. MicroPure combines nonlinear imaging and speckle suppression to mark suspected calcifications as white spots in a blue overlay image. Four independent and blinded readers (2 radiologists and 2 physicists) analyzed 208 digital clips consisting of dual grayscale ultrasound and MicroPure imaging, counting the number of microcalcifications seen with MicroPure. The observers also assessed the level of suspicion on a qualitative, visual analog, 6‐point scale from 0 (no findings) over 1 (benign) to 5 (malignant).

Results

The mean number of microcalcifications ± SD seen was 6.3 ± 3.5, whereas mammography saw 28.9 ± 24.6 (P = .66). When the MicroPure level of suspicion scores were compared with pathologic results using a receiver operating characteristic curve analysis, the areas under the curve ranged from 0.54 to 0.59. Nonetheless, malignant cases were seen to have significantly more microcalcifications than benign cases (mean number of microcalcifications, 6.9 ± 5.1 versus 5.3 ± 3.7; P = .02).

Conclusions

MicroPure can be used to identify areas with breast microcalcifications but cannot effectively characterize such areas. Instead, MicroPure may represent a new imaging method for guiding a biopsy to areas of microcalcifications.
Nosebleeds in hereditary hemorrhagic telangiectasia: Development of a patient‐completed daily eDiary
Authors: Clark Marci , Berry Pamela , Martin Susan , Harris Nimanee , Sprecher Dennis , Olitsky Scott , Hoag Jeffrey B.
Published: November 2018

Objective

A prospective, qualitative study was conducted to develop a patient‐reported outcome measure (PROM) for daily administration via electronic diary (eDiary) to assess the severity of nosebleeds in patients with hereditary hemorrhagic telangiectasia (HHT), in accordance with Food and Drug Administration (FDA) PROM guidance criteria.

Methods

Three expert clinicians who treat patients with HHT provided input during instrument development, which comprised: 1) Peer‐reviewed literature and instrument review; 2) Development of draft Nosebleed Diary items; 3a) Three rounds of qualitative interviews (two with a paper‐based diary, one with an eDiary) with patients with documented severe epistaxis related to HHT, for concept elicitation and cognitive debriefing; 3b) Face validity and translatability assessment; 3c) Patient evaluation of the usability and acceptability of the eDiary device; and 4) Preparation of the final Nosebleed eDiary and conceptual framework.

Results

No existing instruments were identified that evaluate HHT‐related nosebleed severity daily and meet FDA PROM guidance criteria. Frequency, duration, and/or speed of flow (i.e., intensity) were reported by most participants with HHT when asked to describe their nosebleed severity. The Nosebleed eDiary was refined based on 17 patient interviews, clinical expert input and the face validity and translatability assessment. The final four‐item eDiary was acceptable to patients with HHT.

Conclusion

The Nosebleed eDiary is “fit for purpose” to assess the severity of HHT‐related nosebleeds, and has established face and content validity. Further adaptation may be required for use in mild or moderate HHT populations. Psychometric testing to evaluate construct validity and reliability are recommended next steps.

Level of Evidence

2c “Outcomes research”
How information processing and mobile channel choice influence product returns: An empirical analysis
Authors: Seeger Marie K. , Kemper Jan , Brettel Malte
Published: November 2018

The mobile internet is starting to overtake the desktop device‐based internet as a purchase channel. Its impact on consumer behavior is therefore increasingly important to understand. This study seeks to understand and measure, if usage of mobile devices for online purchases leads to a lower decision quality and, in effect, to more product returns. In doing so, the impact of information environments on the end‐to‐end consumer purchase decision‐making process is better understood and it is investigated, if the information environment of mobile devices leads consumers to take more error‐prone purchase decisions. An exclusive data set spanning more than 140 million transactions of a European online retailer is used to empirically analyze changes in product return behavior after mobile channel adoption. The results show that mobile channel usage is positively related to product returns, overall and for both, purchases made with mobile devices and purchases made with desktop devices, although prior literature predicts that returns from desktop purchases should not increase. These findings suggest that through new channels, consumers’ information environment is altered sufficiently to affect their decision accuracy. Moreover, the results indicate that previous research may be overestimating the positive effect of mobile channel adoption on sales by disregarding changes in product return behavior.
Orexin supplementation in narcolepsy treatment: A review
Authors: Nepovimova Eugenie , Janockova Jana , Misik Jan , Kubik Stepan , Stuchlik Ales , Vales Karel , Korabecny Jan , Mezeiova Eva , Dolezal Rafael , Soukup Ondrej , Kobrlova Tereza , Pham Ngoc Lam , Nguyen Thuy Duong , Konecny Jan , Kuca Kamil
Published: November 2018

Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin/hypocretin neuronal loss. The orexin system regulates sleep/wake control via complex interactions with monoaminergic, cholinergic and GABA‐ergic neuronal systems. Currently, no cure for narcolepsy exists, but some symptoms can be controlled with medication (eg, stimulants, antidepressants, etc). Orexin supplementation represents a more sophisticated way to treat narcolepsy because it addresses the underlying cause of the disease and not just the symptoms. Research on orexin supplementation in the treatment of sleep disorders has strongly increased over the past two decades. This review focuses on a brief description of narcolepsy, the mechanisms by which the orexin system regulates sleep/wake cycles, and finally, possible therapeutic options based on orexin supplementation in animal models and patients with narcolepsy.
Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals
Authors: Barnes Ryan C. , Kim Hyemee , Fang Chuo , Bennett William , Nemec Matthew , Sirven Maritza A. , Suchodolski Jan S. , Deutz Nicolaas , Britton Robert A. , Mertens‐Talcott Susanne U. , Talcott Stephen T.
Published: November 2018

Scope

This human clinical pilot trial investigated pharmacokinetics of gallotannin‐metabolites and modulation of intestinal microbiota in healthy lean and obese individuals after 6 weeks of daily mango consumption.

Methods and results

Participants are divided into three groups: Lean Mango (LM: n = 12; BMI = 22.9 kg m−2), Obese Mango (OM: n = 9; BMI = 34.6 kg m−2), and Lean Control (LC: n = 11; BMI = 22.1 kg m−2). LM and OM consumed 400 g of mango per day for 6 weeks. LC consumed mango only on Days 0 and 42. After 6 weeks, LM experienced increased systemic exposure (AUC0–8h) to gallotannin‐metabolites, 1.4‐fold (p = 0.043). The greatest increase is 4‐O‐methyl‐gallic acid, 3.3‐fold (p = 0.0026). Cumulative urinary excretion of gallotannin‐metabolites significantly increased in LM and OM, but not LC. For OM, qPCR data show increased levels of tannase‐producing Lactococcus lactis and decreased levels of Clostridium leptum and Bacteroides thetaiotaomicron, bacteria associated with obesity. LM experienced an increased trend of fecal levels of butyric (1.3‐fold; p = 0.09) and valeric acids (1.5‐fold; p = 0.056). Plasma endotoxins showed a decreased trend in LM and OM.

Conclusion

Continuous mango intake significantly increased systemic exposure to gallotannin‐ metabolites and induced an increased trend for fecal short‐chain fatty acids in lean but not obese individuals. This pharmacokinetic discrepancy may result in BMI‐associated reduced gallotannin‐derived health benefits.
The dimensionality of suicidal ideation and its clinical implications
Authors: Baertschi Marc , Costanza Alessandra , Canuto Alessandra , Weber Kerstin
Published: November 2018

Objectives

No consensus has been reached regarding the theoretical dimensions underlying the Scale for Suicide Ideation (SSI) and Beck's Scale for Suicide Ideation (BSI), widely used in research and clinical practice. This undermines the understanding and management of suicidal behavior.

Methods

The factor structure of the SSI and the BSI was investigated in 201 patients visiting the emergency department of the Geneva University Hospital, Switzerland, for suicidal ideation or a suicide attempt.

Results

Exploratory factor analyses (EFAs) identified a unique theoretical dimension. Item removal based on analyses of communalities improved the explained part of variance in both scales. A joint factor analysis provided results very similar to those yielded by initial EFAs.

Conclusions

The single factor underlying the SSI and the BSI was composed of items encompassing a construct of suicide desire. Nonretained items corresponded to other elements of suicidal behavior (e.g., plans and preparations regarding the upcoming suicide attempt). These scales could not discriminate between suicide ideators and suicide attempters.
Simultaneous estimation of PD, T1, T2, T2*, and ∆B0 using magnetic resonance fingerprinting with background gradient compensation
Authors: Hong Taehwa , Han Dongyeob , Kim Dong‐Hyun
Published: November 2018

Purpose

This study aims to estimate PD, T1, T2, T2*, and B0 simultaneously using magnetic resonance fingerprinting (MRF) with compensation of the linearly varying background field.

Methods

MRF based on fast imaging with steady‐state precession (FISP) and multi‐echo spoiled gradient (SPGR) schemes are alternatively used, which encode T2 and T2*, respectively. Simulations are performed to determine the appropriate ratio of the FISP and SPGR sections with respect to the T2 and T2* accuracy. Additionally, background field inhomogeneity (Gz) compensation using z‐shim gradients are incorporated into the SPGR section and the dictionary. The background field compensation is tested in the phantom experiment under well‐shimmed and poor‐shimmed conditions. An in vivo experiment is performed and the estimated parameters are compared before and after Gz compensation.

Results

The T1, T2, and T2* values from the phantom results are in good agreement with the reference methods under well‐shimmed condition. The underestimated T2 and T2* values under poor‐shimmed condition are recovered by Gz compensation and the parameters are also in good agreement with the reference methods. In the human brain, T2 and T2* values are restored by Gz compensation in regions where the magnetic field is particularly inhomogeneous, such as near the sinus and ear canals.

Conclusions

The proposed FISP and SPGR combined MRF provides a simultaneous estimation of PD, T1, T2, T2*, and B0. By incorporating field inhomogeneity as a gradient term into both the sequence and dictionary, T2 and T2* values can be restored where field inhomogeneity exists.
Phase‐contrast single‐point imaging with synchronized encoding: a more reliable technique for in vitro flow quantification
Authors: Bruschewski Martin , Kolkmannn Hanna , John Kristine , Grundmann Sven
Published: November 2018

Purpose

The purpose of this study is to provide a standard method for flow velocity measurements with phase‐contrast (PC) MRI. This method can be used for in vitro studies that place high demands on measurement accuracy. Clinically relevant PC MRI techniques can be validated using this method before being applied in vivo.

Methods

Many motion‐related errors in PC MRI, particularly flow misregistration, depend on the timing of the encoding gradients in the pulse sequence. By synchronizing all encoding gradients and shortening the overall encoding interval, these errors can be significantly reduced. Based on this concept, a single‐point PC MRI method is proposed.

Results

Flow experiments were conducted in vitro. No considerable errors were found in the velocity data of the proposed method. For comparison, a conventional PC MRI technique showed up to 100% local velocity deviation and up to 35% flow rate deviation in the same experiments.

Conclusions

With the proposed method, the overall measurement accuracy is significantly increased compared to conventional PC MRI techniques. Due to long acquisition times and high specific absorption rates, this method can only be applied in vitro.
Fully coupled hydraulic fracture simulation using the improved element partition method
Authors: Peng Shujun , Zhang Zhennan , Mou Jianye , Zhao Bing , Liu Zhiyuan , Wang Jiading
Published: November 2018

The improved element partition method (IEPM) is a newly developed fracture simulation approach. IEPM allows a fracture to run across an element without introducing extra degrees of freedom. It can also simulate any number of fractures in a prescribed mesh without remeshing. In this study, the IEPM is extended to hydraulic fracture simulation. First, the seepage and volumetric storage matrix of a cracked element are derived using virtual nodes (the intersection points of a crack with element edges). Subsequently, the fully coupled hydromechanical equation is derived for this cracked element. To eliminate the extra degrees of freedom (virtual nodal quantities), the water pressure and displacement of the virtual nodes are associated with their adjacent nodes through least squares interpolation. Finally, the fully coupled equation in terms of nodal quantities is obtained. The verification cases validate the method. By using this method, the field‐scale hydraulic fracturing process is well simulated. The proposed approach is simple and efficient for field‐scale hydraulic fracture simulation.
Glucagon infusion alters the hyperpolarized 13C‐urea renal hemodynamic signature
Authors: Qi Haiyun , Mariager Christian Østergaard , Nielsen Per Mose , Schroeder Marie , Lindhardt Jakob , Nørregaard Rikke , Klein Janet D. , Sands Jeff M. , Laustsen Christoffer
Published: November 2018

Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [13C,15N] urea dynamics and 23Na distribution before and 60 min after glucagon infusion in six female rats.

Glucagon infusion increased the renal [13C,15N] urea mean transit time by 14%, while no change was seen in the sodium distribution, glomerular filtration rate or oxygen consumption. This change is related to the well‐known effect of increased urea excretion associated with glucagon infusion, independent of renal functional effects. This study demonstrates for the first time that hyperpolarized 13C‐urea enables monitoring of renal urinary excretion effects in vivo.
Food Insecurity is Associated with Maladaptive Eating Behaviors and Objectively Measured Overeating
Authors: Stinson Emma J. , Votruba Susanne B. , Venti Colleen , Perez Marisol , Krakoff Jonathan , Gluck Marci E.
Published: November 2018

Objective

The association between food insecurity and obesity may be partially explained by overeating in response to unpredictable food availability cycles. The aim of this study was to measure objective food intake in food‐insecure individuals.

Methods

Eighty‐two volunteers (53 m; BMI 29 ± 7; 38 ± 12 years) were admitted to our inpatient Clinical Research Unit and completed the Food Security Short Form, Three‐Factor Eating Questionnaire, Gormally Binge Eating Scale, and body composition assessment (dual‐energy x‐ray absorptiometry). After 5 days of a weight‐maintaining diet, participants self‐selected food from an ad libitum vending machine paradigm for 3 days. Mean daily intake (kilocalories), macronutrient intake, and percentage of weight‐maintaining energy needs (%WMEN) were calculated.

Results

Based on Food Security Short Form cutoffs, food‐insecure participants (n = 46; 56%) had higher body weight (P = 0.04), fat‐free mass (P = 0.05), disinhibition (P = 0.008), hunger (P = 0.02), and binge‐eating scores (P = 0.02) but not cognitive restraint (P = 0.37) compared with food‐secure individuals. They overate more kilocalories (P = 0.001), %WMEN (P = 0.003), fat (P = 0.003), and carbohydrates (P = 0.004) during the vending machine paradigm, continued to increase their hourly rate of kilocalories (group × time; β = 37.7 cumulative kcal/h; P < 0.0001), and ate more total kilocalories across the 72 hours (β = 47.09 kcal/h; P = 0.003).

Conclusions

Food insecurity may amplify susceptibility to weight gain via overeating during times of unlimited food access.
A Subject Deferred: Exposure and Erasure in an Ethnographic Archive
Authors: Fisher Daniel
Published: November 2018

From as early as the late 1970s anthropologists and ethnomusicologists have been both analysts of and advocates for institutional worlds of Aboriginal art and media. Keenly aware of the Faustian character ascribed to the Indigenous embrace of media, and attuned to the ironies of its governmental subvention, such work of necessity took shape in dialogue with specific institutional possibilities and Australian anxieties. This paper revisits the historical coordinates of Indigenous media research in the age of social media, exploring the relationship between institutional representation and recognition, and the avatars and memes afforded by contemporary social media platforms. Drawing from an ethnographic archive of online media, the essay seeks to better understand the dissimulation and self‐erasure these artefacts entail.
Efficient Synthesis of the N‐(buta‐2,3‐dienyl)carboxamide of Isopimaric Acid and the Potential of This Compound towards Heterocyclic Derivatives of Diterpenoids
Authors: Gromova Marya A. , Kharitonov Yurii V. , Bagryanskaya Irina Yu. , Shults Elvira E.
Published: November 2018

The N‐(2,3‐butadienyl)carboxamide of isopimaric acid, that is, compound 3, was prepared through a two‐step synthetic procedure starting from the natural diterpene isopimaric acid. The Pd‐catalyzed cross‐coupling and subsequent cyclization of terpenoid allene 3 with several aryl iodides and aryl bromides gave access to optically active diterpenoid–oxazoline derivatives in good to excellent yields. The functional group tolerance in the aryl iodides was demonstrated by several examples, including substrates with additional N‐tert‐butoxycarbonyl‐protected amino, hydroxy, and carboxy substituents in the ortho position. The cross‐coupling–cyclization reaction of those compounds with allene 3 proceeded selectively with the formation of cyclization products on the substituent in the aromatic ring. This transformation opens a potential route to the synthesis of hybrid compounds containing a tricyclic diterpenoid and several heterocycles.
Fc‐binding proteins enhance autoantibody‐induced BP180 depletion in pemphigoid
Authors: Iwata Hiroaki , Kamaguchi Mayumi , Ujiie Hideyuki , Ujiie Inkin , Natsuga Ken , Nishie Wataru , Shimizu Hiroshi
Published: November 2018

Immunoglobulins (Igs) consist of two antigen‐binding regions (Fab) and one constant region (Fc). Protein A and protein G are bacterial proteins used for the purification of IgG by virtue of their high affinities for the Fc fragment. Rheumatoid factors are autoantibodies against IgG Fc fragments, which are present in the body under physiological conditions. Little is known about the influence of Fc‐binding proteins on the pathogenicity of antibody‐induced autoimmune diseases. Pemphigoid diseases are a group of autoimmune subepidermal blistering disorders that includes bullous pemphigoid and mucous membrane pemphigoid. IgGs targeting the non‐collagenous NC16A domain of the 180‐kDa bullous pemphigoid antigen (BP180) are known to induce skin fragility in mice and the depletion of BP180 in keratinocytes. In this study, mAb against NC16A in combination with Fc‐binding proteins was found to enhance BP180 depletion. Although mAb against the C‐terminus of BP180 does not show pathogenicity in vivo or in vitro, mAb treatment with Fc‐binding proteins clearly induced skin fragility in mice and BP180 depletion in keratinocytes. Anti‐BP180 mAbs and Fc‐binding proteins were colocalized in the cytoplasm and at the basement membrane zone. Cell adhesion strengths were decreased in parallel with BP180 amounts. Clinically, bullous pemphigoid patients had higher rheumatoid factor titers than controls. Anti‐BP180 mAb in combination with high‐titer rheumatoid factor serum was found to enhance BP180 depletion. Furthermore, saliva from mucous membrane pemphigoid patients contained larger quantities of bacteria and Fc‐binding proteins than controls. Our results suggest that Fc‐binding proteins (rheumatoid factor or protein G) may enhance the pathogenicity of autoantibodies in pemphigoid diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Recent advances in breast cancer research impacting clinical diagnostic practice
Authors: McCart Reed Amy E , Kalita‐De Croft Priyakshi , Kutasovic Jamie R , Saunus Jodi M , Lakhani Sunil R
Published: November 2018

During the last decade, the genomics revolution has driven critical advances in molecular oncology and pathology, and a deeper appreciation of heterogeneity that is beginning to reshape our thinking around diagnostic classification. Recent developments have seen existing classification systems modified and improved where possible, gene‐based diagnostics implemented and tumour–immune interactions modulated. We present a detailed discussion of this progress, including advances in the understanding of breast tumour classification, e.g. mixed ductal–lobular tumours and the spectrum of triple‐negative breast cancer. The latest information on clinical trials and the implementation of gene‐based diagnostics, including MammaPrint and Oncotype Dx and others, is synthesised, and emerging targeted therapies, as well as the burgeoning immuno‐oncology field, and their relevance in breast cancer, are discussed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Using the Patient‐Reported Outcomes Measurement Information System (PROMIS) to measure symptom burden reported by patients with brain tumors
Authors: Lai Jin‐Shei , Kupst Mary Jo , Beaumont Jennifer L. , Manley Peter E. , Chang John Han‐Chih , Hartsell William F. , Kwok Young , Fisher Allison Piazza , Goldman Stewart
Published: November 2018

Background

Children with brain tumors can experience symptom burden throughout their disease continuum. The aim of the study was to evaluate symptom burden reported by children with brain tumors and factors that potentially were associated with their symptoms.

Methods

Data from 199 children with brain tumors aged 7–22 (mean age = 14 years; 52% males; 76% white) were analyzed. Symptom burden was assessed using the Patient‐Reported Outcomes Measurement Information System (PROMIS) via computerized adaptive testing (CAT)—anxiety, depression, fatigue, mobility, upper extremity function, peer relationship, and cognition. Patients and parents completed Symptom Distress Scales (SDS). Test statistics and ANOVA were used to evaluate relationships between PROMIS measures and potentially influential variables.

Results

Significant results (P < 0.01) showing impact of symptom burden included: PROMIS measures correlated with SDSs reported by patients and parents on all comparisons. Fatigue, mobility, and upper extremity function were associated with Karnofsky functional performance status, number of treatment modalities (0–3), and time since last treatment (≤1 year, >1 year). Fatigue and cognition were associated with educational program (regular classroom without an individualized education plan vs those that had an individualized education plan); mobility and upper extremity function were associated with time since last radiation. Mobility, upper extremity function, and anxiety were associated with time since last chemotherapy.

Conclusions

Significant associations were found between PROMIS and SDS as well as clinical and demographic characteristics. Brief‐yet‐precise PROMIS CATs can be used to systematically assess symptom burden experienced by children with brain tumors.
Optimization of dielectric properties of PVDF–CFO nanocomposites
Authors: Supriya Sweety , Kumar Lawrence , Kar Manoranjan
Published: November 2018

Incorporation of different types of nanofillers in the PVDF poly(vinylidene difluoride) matrix exhibits promising dielectric, magnetic, piezo, pyro, and ferroelectric properties for various applications. Hence a novel nanocomposite has been developed by using PVDF and cobalt ferrite (CFO) (CoFe2O4) with different particle size of CFO for dielectric applications. The nanocomposite has been characterized by the X‐ray diffraction pattern, atomic force microscopy, transmission electron microscopy, fourier transform infra‐red spectroscopy, field emission‐scanning electron microscopy), and dielectric measurements. The space charge effect at the PVDF and CFO interfaces offers the interfacial polarization in nanocomposite, which contribute to tune the dielectric response of nanocomposite along with low dielectric loss. The filler size has been optimized to have better formation of polar β phase in PVDF along with high dielectric properties. The dielectric constant in nanocomposite has increased three times compare to that of PVDF. The 20 ± 1 nm size (CFO) filler in PVDF matrix exhibits optimized dielectric properties. POLYM. COMPOS., 40:1239–1250, 2019. © 2018 Society of Plastics Engineers
Parent–teacher problem solving about concerns in children with autism spectrum disorder: The role of income and race
Authors: Azad Gazi F. , Gormley Sara , Marcus Steve , Mandell David S.
Published: November 2018

Problem solving between parents and teachers is critical to maximizing student outcomes. The current study examined the associations among the different components of problem solving, as well as the relationship between various characteristics and problem solving in parents and teachers of children with autism spectrum disorder (ASD). Participants were 18 teachers and 39 parents of children with ASD. Parents and teachers completed a demographic survey, phone interview, and dyad observation. Results indicated that parent and teacher problem solving strategies were correlated with each other. Lower‐income parents and parents interacting with White teachers displayed less problem solving. Findings suggest that school‐based service delivery models to improve problem solving should consider both skill development, as well as the sociodemographic characteristics that parents and teachers bring to their interactions.
Thermal states, responsiveness and degradation of marginal permafrost in Mongolia
Authors: Ishikawa Mamoru , Jamvaljav Yamkhin , Dashtseren Avirmed , Sharkhuu Natsagdorj , Davaa Gamboo , Iijima Yoshihiro , Baatarbileg Nachin , Yoshikawa Kenji
Published: November 2018

Ground thermal conditions in marginal permafrost in Mongolia were assessed using ground temperatures measured year‐round at 69 borehole sites. Permafrost is continuous in northern Mongolia and exists as sporadic/isolated patches in the south. Ground temperatures are strongly controlled by local environmental factors, such as topographic depressions that concentrate cold air during winter, ice‐rich strata that prevent penetration of sensible heat, and tree cover that reduces incident solar radiation. Permafrost temperatures are typically between −1 and 0°C; colder permafrost (< −2°C) occurs in the northern extent of continuous permafrost and at high elevations in the sporadic/isolated permafrost zones. Relict permafrost, which is thermally disconnected from seasonal air temperature fluctuations, is present near the latitudinal and elevational limits of perennially frozen ground. Cold and thermally responsive permafrost is dominant in the continuous and discontinuous zones, while warm and thermally unresponsive permafrost is dominant in the sporadic and isolated zones. Overall, the climate‐driven permafrost in the colder regions is stable, while the ecosystem‐driven permafrost in the warmer regions is degrading.
Near‐Infrared Laser Initiation Mechanism of Pentaerythritol Tetranitrate Doped with Aluminum Nanoparticles
Authors: Ji Xiangbo , Qin Wenzhi , Tang Duo , Gao Yuan , Li Yong , Wang Liang , Liu Yonggang
Published: November 2018

Aluminum nanoparticles were added into pentaerythritol tetranitrate (PETN) to decrease the near‐infrared (NIR) laser initiation power. The effects of Al nanoparticles on the minimum power of all fire were investigated under 1064 nm laser initiation. The initiation mechanism was studied using differential scanning calorimetry, reflectance spectroscopy, laser‐induced breakdown spectroscopy, and shadowgraph technique. Results showed that the addition of Al nanoparticles could prominently decrease the minimum power of all fire of PETN. The PETN doped with 0.5 % Al nanoparticles could be reliably initiated with 40 mJ laser energy (1064 nm, 14 ns). However, the increase in Al nanoparticles increased the minimum power of all fire. A thermal mechanism could be affirmed for the initiation of PETN doped with Al nanoparticles with the NIR laser initiation. First, Al nanoparticles were heated to high temperature to form hotspots by absorbing input NIR laser energy. Then, the PETN surrounded by the hotspots propagated self‐sustaining chemical reactions and exploded. With the increase of Al nanoparticles, the increase in thermal conductivity and the decrease of the hot‐spots temperature resulted in high laser power to initiate explosives.
Numerical Research on Initiation of PBXC03 Explosives under Quasi‐Isentropic Loadings
Authors: Liu Hai Qing , Duan Zhuo Ping , Li Shu Rui , Ou Zhuo Chen , Bai Zhi Ling , Huang Feng Lei
Published: November 2018

To study the influence of different quasi‐isentropic loading modes on the ignition and the detonation growth processes of PBXs, a one‐dimensional numerical model based on the DZK reaction rate model is presented, and then the parameters of DZK reaction rate model of PBXC03 can be experimental calibrated under the quasi‐isentropic loadings. Moreover, the ignition and detonation growth processes of PBXC03 under different quasi‐isentropic loading modes are simulated by using DYNA2D. It is found from the numerical results that both the increase of the peak pressure of shock front and the shock wave speed increase but the time to detonation decreases with the peak loading pressure, loading slope and curvature. It is also found that the explosive initiation process under the quasi‐isentropic loadings can be divided into two stages: one is the initial stage that manifests mainly as the catch‐up and convergence of the quasi‐isentropic waves and the formation of shock waves; the other is the stage of shock initiation, in which a shock wave with a certain intensity is formed and grows gradually into a stable detonation wave. In addition, a necessary condition is proposed to discriminate the feasibility of an quasi‐isentropic loading experimental calibration of the EOS parameters of a unreacted explosive, i. e., the sample's thickness must be smaller than the thickness of initial reaction.
Mitochondrial complex III Qi‐site inhibitor resistance mutations found in laboratory selected mutants and field isolates
Authors: Mounkoro Pierre , Michel Thomas , Benhachemi Rafik , Surpateanu Georgiana , Iorga Bogdan I , Fisher Nicholas , Meunier Brigitte
Published: November 2018

BACKGROUND

Complex III inhibitors targeting the Qi‐site have been known for decades; some are used or being developed as antimicrobial compounds. Target site resistance mutations have been reported in laboratory‐selected mutants and in field isolates. Here, we present a brief overview of mutations found in laboratory‐selected resistant mutants. We also provide a study of mutations observed in field isolates of Plasmopara viticola, in particular the ametoctradin resistance substitution, S34L that we analysed in the yeast model.

RESULTS

A survey of laboratory mutants showed that resistance could be caused by a large number of substitutions in the Qi‐site. Four residues seemed key in term of resistance: N31, G37, L198 and K228. Using yeast, we analysed the effect of the ametoctradin resistance substitution S34L reported in field isolates of P. viticola. We showed that S34L caused a high level of resistance combined with a loss of complex III activity and growth competence.

CONCLUSION

Use of single site Qi‐site inhibitors is expected to result in the selection of resistant mutants. However, if the substitution is associated with a fitness penalty, as may be the case with S34L, resistance development might not be an insuperable obstacle, although careful monitoring is required. © 2018 Society of Chemical Industry
Reducing Palivizumab Dose Requirements Through Rational Dose Regimen Design
Authors: Reuter Stephanie E. , Evans Allan M. , Ward Michael B.
Published: November 2018

Palivizumab for respiratory syncytial virus (RSV) immunoprophylaxis in premature infants poses a significant economic challenge. Although standard dosing of palivizumab results in unnecessary drug accumulation without additional clinical benefit, some clinicians have moved outside of evidence‐based practice by implementing untested dose modifications, potentially jeopardizing efficacy. Using an industry‐developed population pharmacokinetic model, this study evaluated the previously published alternate dosing regimens and developed a revised regimen that minimizes palivizumab dose requirements while maintaining established therapeutic concentrations. All published dose modifications resulted in unacceptably high proportions of infants not attaining minimum protective concentrations, compromising efficacy. Through intelligent dose regimen design, a clinically practical palivizumab regimen was devised that reduces drug use by 25%, while enabling a greater proportion of infants attaining early season target concentrations, particularly those at greatest risk of the consequences of RSV infection. This novel regimen has the potential to substantially change clinical practice and increase drug availability.
Randomized, double‐blind, placebo‐controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy
Authors: Saadipoor Afshin , Razzaghdoust Abolfazl , Simforoosh Nasser , Mahdavi Arash , Bakhshandeh Mohsen , Moghadam Maryam , Abdollahi Hamid , Mofid Bahram
Published: November 2018

Clinical potential of curcumin in radiotherapy (RT) setting is outstanding and of high interest. The main purpose of this randomized controlled trial (RCT) was to assess the beneficial role of nanocurcumin to prevent and/or mitigate radiation‐induced proctitis in prostate cancer patients undergoing RT. In this parallel‐group study, 64 eligible patients with prostate cancer were randomized to receive either oral nanocurcumin (120 mg/day) or placebo 3 days before and during the RT course. Acute toxicities including proctitis and cystitis were assessed weekly during the treatment and once thereafter using CTCAE v.4.03 grading criteria. Baseline‐adjusted hematologic nadirs were also analyzed and compared between the two groups. The patients undergoing definitive RT were followed to evaluate the tumor response. Nanocurcumin was well tolerated. Radiation‐induced proctitis was noted in 18/31 (58.1%) of the placebo‐treated patients versus 15/33 (45.5%) of nanocurcumin‐treated patients (p = 0.313). No significant difference was also found between the two groups with regard to radiation‐induced cystitis, duration of radiation toxicities, hematologic nadirs, and tumor response. In conclusion, this RCT was underpowered to indicate the efficacy of nanocurcumin in this clinical setting but could provide a considerable new translational insight to bridge the gap between the laboratory and clinical practice.
Overall indices for assessing agreement among multiple raters
Authors: Jang Jeong Hoon , Manatunga Amita K. , Taylor Andrew T. , Long Qi
Published: November 2018

The need to assess agreement exists in various clinical studies where quantifying inter‐rater reliability is of great importance. Use of unscaled agreement indices, such as total deviation index and coverage probability (CP), is recommended for two main reasons: (i) they are intuitive in a sense that interpretations are tied to the original measurement unit; (ii) practitioners can readily determine whether the agreement is satisfactory by directly comparing the value of the index to a prespecified tolerable CP or absolute difference. However, the unscaled indices were only defined in the context of comparing two raters or multiple raters that assume homogeneity of variances across raters. In this paper, we introduce a set of overall indices based on the root mean square of pairwise differences that are unscaled and can be used to evaluate agreement among multiple raters that often exhibit heterogeneous measurement processes in practice. Furthermore, we propose another overall agreement index based on the root mean square of pairwise differences that is scaled and extends the concept of the recently proposed relative area under CP curve in the presence of multiple raters. We present the definitions of overall indices and propose inference procedures in which bootstrap methods are used for the estimation of standard errors. We assess the performance of the proposed approach and demonstrate its superiority over the existing methods when raters exhibit heterogeneous measurement processes using simulation studies. Finally, we demonstrate the application of our methods using a renal study.
NCN Nickel(II) Pincer Complexes of 5‐tert‐Butyl‐1,3‐bis(N‐substituted benzimidazol‐2′‐yl)benzenes: Solid and Solution State Behaviour
Authors: Rani Varsha , Singh Harkesh B. , Butcher Ray J.
Published: November 2018

A series of square planar NCN nickel(II) pincer complexes; [Methyl(N C N)NiBr] (14), [Benzyl(N C N)NiBr] (15), [Benz°yl(N C N)NiBr] (16), and [Pentyl(N C N)NiBr] (17) [(N C N)=5‐tert‐butyl‐1,3‐bis(N‐substituted benzimidazol‐2′‐yl)phenyl] have been synthesized by the treatment of nickel(0) precursor, Ni(COD)2 [COD=1,5‐cyclooctadiene] with 5‐tert‐butyl‐1,3‐bis‐(N‐substituted‐benzimidazol‐2′‐yl)‐2‐bromobenzenes via oxidative addition in 44–74% yield. The formation of complexes 14–17 was confirmed by elemental analysis, mass spectrometry. Complexes 14 and 15 are poorly soluble in common organic solvents, however, complexes 16 and 17 are fairly soluble in CDCl3. The structure of complex 17 was further corroborated by X‐ray crystallographic studies. Interestingly, the bromide anion bonded to nickel is found to be very labile and it is easily substituted with methoxy group. The formation of the methoxy complex 18 is more facile as compared with related PCsp3P nickel pincer complex [(C6H4PPri2)2CH−NiBr] reported in literature.
Highly Compact Artificial Memristive Neuron with Low Energy Consumption
Authors: Zhang Yishu , He Wei , Wu Yujie , Huang Kejie , Shen Yangshu , Su Jiasheng , Wang Yaoyuan , Zhang Ziyang , Ji Xinglong , Li Guoqi , Zhang Hongtao , Song Sen , Li Huanglong , Sun Litao , Zhao Rong , Shi Luping
Published: November 2018

Neuromorphic systems aim to implement large‐scale artificial neural network on hardware to ultimately realize human‐level intelligence. The recent development of nonsilicon nanodevices has opened the huge potential of full memristive neural networks (FMNN), consisting of memristive neurons and synapses, for neuromorphic applications. Unlike the widely reported memristive synapses, the development of artificial neurons on memristive devices has less progress. Sophisticated neural dynamics is the major obstacle behind the lagging. Here a rich dynamics‐driven artificial neuron is demonstrated, which successfully emulates partial essential neural features of neural processing, including leaky integration, automatic threshold‐driven fire, and self‐recovery, in a unified manner. The realization of bioplausible artificial neurons on a single device with ultralow power consumption paves the way for constructing energy‐efficient large‐scale FMNN and may boost the development of neuromorphic systems with high density, low power, and fast speed.
Modeling and simulation of a turbulent‐like thermal plasma jet for nanopowder production
Authors: Shigeta Masaya
Published: November 2018

This paper discusses theoretical models and numerical methods to simulate turbulent thermal plasma flow transporting a nanopowder. In addition to a thermal plasma flow model, a sophisticated model is described mathematically for the nanopowder's collective growth by homogeneous nucleation, heterogeneous condensation, and coagulation among nanoparticles, and also transport by convection, diffusion, and thermophoresis, simultaneously. Demonstrative simulations show clearly that a suitable numerical method with high‐order accuracy should be used for long and robust simulation capturing multiscale eddies and steep gradients of temperature, which are the turbulent features of thermal plasma flows with locally variable density, transport properties and Mach numbers. Eddies are first generated at the interfacial region between the plasma jet and ambient nonionized gas by fluid‐dynamic instability. As a result of the eddies' generation–breakup process, the plasma flow entrains the ambient cold gas and deforms its shape traveling downstream. Numerous sub‐nanometer particles are generated by nucleation and condensation in the thin layers near the plasma jet. Those particles diffuse and increase their size, thus decreasing their number by coagulation. Cross‐correlation analysis suggests that the nanopowder distribution distant from a plasma jet can be controlled by controlling the temperature fluctuation at the upstream plasma fringe. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.