bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered frontal aslant tracts as a heritable neural basis of social communication deficits in autism spectrum disorder: A sibling study using tract‐based automatic analysis
Authors: Lo Yu‐Chun , Chen Yu‐Jen , Hsu Yung‐Chin , Chien Yi‐Ling , Gau Susan Shur‐Fen , Tseng Wen‐Yih Isaac
Published: December 2018

Investigating social behaviors and brain structural alterations in unaffected siblings of individuals with autism spectrum disorder (ASD) may help identify intermediate phenotypes of social communication deficits in ASD. This study hypothesized that such intermediate phenotypes could be identified in white matter tracts of the social communication model that exhibited reduced tract integrity and associations with social communication deficits. Boys with ASD (N = 30), unaffected male siblings (N = 27), and typically developing (TD) boys (N = 30) underwent clinical evaluation and MRI scanning. Group differences in generalized fractional anisotropy (GFA) values, a white matter integrity index derived from diffusion MRI data, and the relationships of GFA with the Social Responsiveness Scale (SRS) scores and the Child Behavior Checklist (CBCL/4–18) scores were investigated. Significant differences were found in the GFA values of the frontal aslant tract (FAT) among the three groups, with the decreasing order of GFA from TD to siblings to ASD. The GFA values of the FAT were associated with the social communication scores (on the SRS) in the sibling group, and those of the superior longitudinal fasciculus III were associated with the social problems scores (on the CBCL/4–18) in the boys with ASD. Due to the altered tract integrity and association with social communication deficits in the unaffected siblings of individuals with ASD, the FAT might be a heritable neural basis for social communication deficits of ASD. Autism Res 2019, 12: 225–238 © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Autism spectrum disorder (ASD) is a group of highly heritable disorders with social communication deficits as one of the core symptoms. This study aimed to identify a neural trait of social communication deficits in individuals with ASD. We investigated brain structural alterations and their associations with social communication scores in unaffected siblings of individuals with ASD. The siblings' frontal aslant tract was found to be impaired, and this tract showed a significant association with the social communication scores. Our findings support that the frontal aslant tract might be a potential neural trait of social communication deficits in ASD.
A molecularly imprinted polymer based chemiluminescence array sensor for one‐step determination of phenothiazines and benzodiazepines in pig urine
Authors: Xia Wan Qiu , Zhang Hui Cai , Wang Geng Nan , Liu Jing , Wang Jian Ping
Published: December 2018

The residues of phenothiazines and benzodiazepines in foods of animal origin are dangerous to consumers. For inspection of their abuses, this study for the first time reported on the use of a chemiluminescence array sensor for the simultaneous determination of four phenothiazines and five benzodiazepines in pig urine. Two molecularly imprinted polymers were coated in different wells of a conventional 96‐well microtiter plate as the recognition reagents. After sample loading, the absorbed analytes were initiated directly by using an imidazole enhanced bis(2,4,6‐trichlorophenyl)oxalate–hydrogen peroxide system to emit light. The assay process consisted of only one sample‐loading step prior to data acquisition, so one test was finished within 10 min. The limits of detection for the nine drugs in the pig urine were in a range of 0.1 to 0.6 pg/mL, and the recoveries from the fortified blank urine samples were in a range of 80.3 to 95%. Furthermore, the sensor could be reused six times. Therefore, this sensor could be used as a simple, rapid, sensitive and reusable tool for routine screening for residues of phenothiazines and benzodiazepines in pig urine.
Suspension Polymerization of Thermally Expandable Microspheres Using Cinnamonitrile and Diethyl Fumarate as Crosslinking Agents
Authors: Kim Hyun Tae , Jaladi Ashok Kumar , Kim Jea Ho , Gundeti Shankaraiah , An Duk Keun
Published: December 2018

Thermally expandable microspheres (TEMs) were synthesized via suspension polymerization using acrylonitrile as the major monomer. Methyl methacrylate and methacrylonitrile were used as supporting co‐monomers, and 1,4‐butanediol dimethacrylate was used as a crosslinking agent. In addition, cinnamonitrile (CN) and diethyl fumarate (DEF) were investigated as monomers to improve the expansion performance of the TEMs. However, the expandability of the TEMs using CN was diminished. When TEMs were prepared with DEF as the crosslinking agent, the expandability was highly affected. From the thermomechanical analysis of TEMs with various crosslinking agents, DEF showed better performance as crosslinking agent, yielding increased expansion properties. This is the first report using DEF as a TEM crosslinking agent.
Comparative effectiveness of radiotherapy for early‐stage hormone receptor‐positive breast cancer in elderly women using real‐world data
Authors: Ali Askal A. , Tawk Rima , Xiao Hong , Campbell Ellen , Semykina Anastasia , Montero Alberto J. , Mogos Muluberhan , Diaby Vakaramoko
Published: December 2018

Background

Radiotherapy is the recommended treatment after breast‐conserving surgery (BCS) for early‐stage breast cancer (BC). However, there is no clear evidence whether radiotherapy after BCS improves the survival of elderly women diagnosed with early‐stage hormone receptor‐positive (HR+) BC. The aim of this study was to investigate the survival benefit associated with radiotherapy plus hormonal therapy vs hormonal therapy alone after BCS for early‐stage HR+ BC patients.

Methods

Using the Surveillance, Epidemiology, and End Results linked with Medicare data, we identified elderly (65 years and older) women diagnosed with early‐stage HR+ BC (2006‐2011) who received hormonal therapy with or without radiotherapy after BCS. A log‐rank test, Cox proportional hazards models, and propensity score matching were used to estimate the overall survival (OS) benefit associated with radiotherapy after BCS.

Results

Of the 5688 patients, there were 303 deaths from any cause. One hundred and eighty‐five (61%) of these deaths occurred in the hormonal therapy group, and 118 (39%) deaths occurred in the radiotherapy plus hormonal therapy group. The mean survival time in the radiotherapy plus hormonal therapy group was 5.32 ± 1.86 years compared with 4.92 ± 1.86 years in the hormonal therapy group. Based on the adjusted and propensity score matching analysis, patients in the adjuvant radiotherapy group had a lower risk of death compared with those who did not receive radiotherapy. Radiotherapy plus hormonal therapy decreased the risk of death by 32%. The effect estimates were similar in the adjusted and matched cohorts.

Conclusions

Radiotherapy plus hormonal therapy resulted in a significant improvement in the OS of elderly women diagnosed with HR+ BC.
Carboxylic Acids Production via Electrochemical Depolymerization of Lignin
Authors: Di Marino Davide , Jestel Tim , Marks Caroline , Viell Jörn , Blindert Malte , Kriescher Stefanie M. A. , Spiess Antje C. , Wessling Matthias
Published: December 2018

Facing the challenge of lignin valorization is one of the unsolved key steps for a sustainable and economically feasible biorefinery. Several processes were developed with the aim of producing value‐added compounds from lignin. Thermal, enzymatic, and catalytic processes represent common techniques for lignin valorization. However, expensive catalysts or enzymes and harsh conditions hampered the implementation of these methodologies on an industrial scale. Here, we propose the utilization of a simple “swiss‐roll” electrochemical reactor for the production of valuable carboxylic acids. We showcase that production of phenolic compounds, such as vanillin, is hindered by the electrochemical mechanism. Additionally, electrochemical stability experiments of possible products showed high reactivity of vanillin against the low reactivity of mono‐ and dicarboxylic acids. Simultaneously, the electrochemical process leads to stable carboxylic acids with high yields of 6.4, 26.8, and 4.2 % for oxalic, formic, and acetic acids, respectively, thus representing a competitive alternative to the catalytic and hydrothermal degradation process for the production of carboxylic acids.
Epigenetic analysis identifies factors driving racial disparity in prostate cancer
Authors: Rai Richa , Yadav Shalini S. , Pan Heng , Khan Irtaza , O'Connor James , Alshalalfa Mohammed , Davicioni Elai , Taioli Emanuela , Elemento Olivier , Tewari Ashutosh K. , Yadav Kamlesh K.
Published: December 2018

Background

Prostate cancer (PCa) is the second most leading cause of death in men worldwide. African‐American men (AA) represent more aggressive form of the disease compared to Caucasian (CA) counterparts. Several lines of evidences suggest that biological factors are responsible for the observed racial disparity.

Aim

This study was aimed at identifying the epigenetic variation among AA and CA PCa patients and whether DNA methylation differences have an association with clinical outcomes in the two races.

Methods and results

The cancer genome atlas (TCGA) dataset (2015) was used to identify existing epigenetic variation in AA and CA PCa patients. Reduced Representation Bisulfite Sequencing (RRBS) was performed to identify global DNA methylation changes in a small cohort of AA and CA PCa patients. The RRBS data were then used to identify survival and recurrence outcomes in AA and CA PCa patients using publicly available datasets. The TCGA data analysis revealed epigenetic heterogeneity, which could be categorized into four classes. AA associated primarily to methylation cluster 1 (p = 0.048), and CA associated to methylation cluster 3 (p = 0.000146). Enrichment of the Wnt signaling pathway was identified in both the races; however, they were differentially activated in terms of canonical and non‐canonical Wnt signaling. This was further validated using the Decipher Genomics Resource Information Database (GRID). The RRBS data also identified discrete methylation patterns in AA compared with CA and, in part, validated our TCGA findings. Survival analysis using the RRBS data suggested hypomethylated genes to be significantly associated with recurrence of PCa in CA (p = 6.07 × 10−6) as well as in AA (p = 0.0077).

Conclusion

Overall, we observed epigenetic‐based racial disparity in PCa which could affect survival and should be considered during prognosis and treatment.
Synthesis and Properties of 3‐Azido‐2,2‐bis(azidomethyl)propyl 2‐Azidoacetate: A Potential Azido Ester Plasticizer
Authors: Wang Yinglei , Liu Yajing , Lu Tingting , Gao Fulei , Zhao Baodong
Published: December 2018

This study reports the synthesis and characterization of a novel azido ester plasticizer, 3‐azido‐2,2‐bis(azidomethyl)propyl 2‐azidoacetate (ABAMPA), with good yield and high purity. The density, impact sensitivity, friction sensitivity, thermal decomposition temperature and glass transition temperature were determined to be 1.326 g ⋅ cm−3, 16 J, 324 N, 235.9 °C and −50.4 °C, respectively. The plasticizing effect of ABAMPA on glycidyl azide polymer (GAP) was calculated by molecular dynamics, the solubility parameter difference value was 1.7(J ⋅ cm−3)0.5, and the glass transition temperature of GAP was reduced from −35 °C to −43 °C when the weight ratio of ABAMPA and GAP was 50 : 50. The new azido ester exhibits high energy, remarkable thermostability and good compatibility with GAP, which indicates that it would have potential application in explosive and propellant formulations.
Outage probability bound of decode and forward two‐way full‐duplex relay employing spatial modulation over cascaded α − μ channels
Authors: Bhowal Anirban , Kshetrimayum Rakhesh Singh
Published: December 2018

The system performance of mobile‐to‐mobile (D2D) cooperative communication has been improved by utilizing spatial modulation (SM) in this paper. The proposed system employs decode and forward (DF) relaying technique along with physical layer network coding (PLNC); hence, it has been named as SM‐based decode and forward two‐way relay (DFTWR). It enables full‐duplex communication thereby enhancing the system efficiency. Information bits are exchanged between the two bidirectional nodes. For two bits of information exchange, the antenna index is conveyed by the least significant bit (LSB) of the data symbol while the most significant bit (MSB) carries the message. The system performance has been investigated by analyzing certain performance metrics like lower and upper bounds of outage probability and average data rate for N‐α‐μ cascaded fading channels. The change in the system performance by varying certain parameters like relative geometrical gain, fading coefficients, and number of cascaded components has also been put forth in this paper.
Secrecy Performance of CCRN with an EHAF Relay under Source and Destination Jamming
Authors: Sharma Shashibhushan , Dhar Roy Sanjay , Kundu Sumit
Published: December 2018

In this paper, we investigate the secrecy performance of a cooperative cognitive radio network (CCRN) considering a single energy harvesting (EH) half‐duplex amplify and forward (AF) relay and an eavesdropper (EAV). Power is allocated to each node under cognitive constraints. Because of the absence of a direct wireless link, secondary source (SS) communicates with secondary destination (SD) in two time slots. The SD and the SS broadcast jamming signal to confuse the EAV in the first and in the second time slots, respectively. The relay harvests energy in the first time slot and amplifies and forwards the signal to SD in the second time slot. The EAV employs maximal ratio combining scheme to extract the information. We evaluate the performance in terms of secrecy outage probability (SOP) of the proposed CCRN. The approximate expression of SOP is obtained in integration form. Improvement in SOP is expected for the proposed CCRN because of the use of jamming signals. The secrecy performance of CCRN improves with increase in primary transmit power, peak transmit power of secondary nodes, channel mean power, and energy conversion efficiency but degrades with increase in threshold outage rate of primary receiver and threshold secrecy rate. A MATLAB‐based simulation framework has been developed to validate the analytical work.
Tadalafil: 15 years' journey in male erectile dysfunction and beyond
Authors: Ahmed Nermin S.
Published: December 2018

Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)‐6‐(1,3‐benzodioxol‐5‐yl)‐2‐methyl‐2,3,6,7,12,12a‐hexahydropyrazino[1′,2′:1,6] pyrido[3,4‐b]indole‐1,4‐dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. The cis‐(6R, 12aR) enantiomer is the most active enantiomer. Tadalafil showed PDE5 inhibition with IC50 = 5 nM. It possesses high selectivity for PDE5 versus PDE1‐4 and PDE6. Tadalafil is more selective to PDE5 against PDE6 whereas sildenafil, another commercially available PDE5 inhibitor shows similar potencies to inhibit PDE5 and PDE6. Tadalafil is used for the treatment of male erectile dysfunction (MED), prostatic benign hyperplasia (PBH) signs and symptoms, and pulmonary arterial hypertension (PAH). Adcirca, another name for tadalafil, is used to treat PAH and improve exercise capacity. Recent clinical studies suggest the use of tadalafil for nonurological applications, including circulatory disorders (ischemia injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, and stroke), neurodegenerative disorders, and cognitive impairment conditions. This review discusses tadalafil and its analogues reported in the past 15 years. It discusses synthetic pathways, structural activity relationships, existing and future pharmacological indications of tadalafil and its analogues. This work can help medicinal chemists developing novel PDE5 inhibitors with wider therapeutic indications.
Resolving reading disability—Childhood predictors and adult‐age outcomes
Authors: Eloranta Anna‐Kaija , Närhi Vesa M. , Eklund Kenneth M. , Ahonen Timo P.S. , Aro Tuija I.
Published: December 2018

We examined frequency of adult‐age reading disability (RD) and its childhood predictors among 48 adults (20 to 39 years) with documented childhood RD, and contrasted their cognitive skills, education, and employment with 37 matched controls. Among individuals with childhood RD, more than half had improved in their reading fluency to the level where the set criterion for adult‐age RD was not met anymore. More fluent rapid naming, less severe childhood RD, and multiple support providers in childhood together predicted improvement of reading fluency. More fluent naming differentiated the childhood RD participants whose reading fluency had improved by adult‐age from those participants whose RD persisted to adult‐age. All the individuals with childhood RD performed weaker than the controls in adult‐age working memory, processing speed, and verbal skills. Educational level among both RD groups was lower than that among the controls. Unemployment of individuals with persistent adult‐age RD (31.6%) was higher than that of individuals with improved adult‐age RD (13.8%) or that of the controls (8.1%). According to our findings, rapid naming is one evident factor differentiating individuals with persisted RD from those with ameliorated reading fluency. Also, better adult‐age reading fluency has significance for adult‐age employment among individuals with childhood RD.
Grasping the weight cut‐off for anorexia nervosa in children and adolescents
Authors: Andersen Susanne B. , Lindgreen Pil , Rokkedal Kristian , Clausen Loa
Published: December 2018

Objective

The Diagnostic and Statistical Manual of Mental Disorders 5 suggests the 5th age‐adjusted body mass index (BMI) percentile as the numeric cut‐off for anorexia nervosa (AN) in children and adolescents. We aimed to investigate the degree to which the 5th age‐adjusted percentile as the numeric cut‐off for AN in youths reflects the clinical population of patients accepted for treatment.

Method

From a specialized eating disorder clinic, 305 patients with AN below 18 years of age were grouped according to age‐adjusted BMI percentiles [below the 5th (low), above the 10th (high), and between the 5th and the 10th (medium)]. The distribution of eating disorder diagnoses and severity measured by the Eating Disorder Examination was compared.

Results

Full‐syndrome anorexia nervosa (F.50.0) was found in 182 (59.5%) patients and atypical anorexia nervosa (F.50.1) in 123 patients (40.5%). The number of patients in the low, medium, and high BMI percentile groups was 189 (62.0%), 34 (11.1%), and 82 (26.9%), respectively. Patients in the low BMI group differed from patients in the medium BMI group by a lower frequency of vomiting. The high BMI group presented with more weight and shape concern than the lower BMI group. Age was not a confounder of these associations.

Discussion

We question the applicability of the 5th BMI percentile as a substantiated cut‐off for the weight criterion in anorexia nervosa in youths and argue that the cut‐off should not be ascribed great clinical importance as this may hinder early detection of illness and initiation of treatment.
Stable isotopes as tracers of trophic interactions in marine mutualistic symbioses
Authors: Ferrier‐Pagès Christine , Leal Miguel Costa
Published: December 2018

Mutualistic nutritional symbioses are widespread in marine ecosystems. They involve the association of a host organism (algae, protists, or marine invertebrates) with symbiotic microorganisms, such as bacteria, cyanobacteria, or dinoflagellates. Nutritional interactions between the partners are difficult to identify in symbioses because they only occur in intact associations. Stable isotope analysis (SIA) has proven to be a useful tool to highlight original nutrient sources and to trace nutrients acquired by and exchanged between the different partners of the association. However, although SIA has been extensively applied to study different marine symbiotic associations, there is no review taking into account of the different types of symbiotic associations, how they have been studied via SIA, methodological issues common among symbiotic associations, and solutions that can be transferred from one type of association with another. The present review aims to fill such gaps in the scientific literature by summarizing the current knowledge of how isotopes have been applied to key marine symbioses to unravel nutrient exchanges between partners, and by describing the difficulties in interpreting the isotopic signal. This review also focuses on the use of compound‐specific stable isotope analysis and on statistical advances to analyze stable isotope data. It also highlights the knowledge gaps that would benefit from future research.
Species and genetic diversity are not congruent in fragmented dry grasslands
Authors: Reisch Christoph , Schmid Christoph
Published: December 2018

Biological diversity comprises both species diversity (SD) and genetic diversity (GD), and it has been postulated that both levels of diversity depend on similar mechanisms. Species‐genetic diversity correlations (SGDC) are therefore supposed to be generally positive. However, in contrast to theory, empirical data are contradictory. Furthermore, there is a pronounced lack of multispecies studies including also the ecological factors potentially driving species and genetic diversity. We analyzed the relationship between the species diversity of dry grasslands and the genetic diversity of several dry grassland plant species, therefore, in the context of habitat fragmentation and habitat conditions. Our study revealed a lack of correlation between species and genetic diversity. We demonstrated previously that SD mainly depends on habitat conditions (vegetation height and cover of litter), whereas GD is significantly affected by habitat fragmentation (distance to the nearest dry grassland in 1830 and connectivity in 2013). This seems to be the main reason why SD and GD are not congruent in fragmented grasslands. Our results support, hence, the observation that positive SGDCs can mainly be found in natural, island‐like study systems in equilibrium and at similar levels of heterogeneity. In fragmented dry grassland ecosystems, which differ in heterogeneity, this state of equilibrium may not have been reached mitigating the positive relationship between SD and GD. From our study, it can be concluded that in fragmented dry grasslands, the protection of SD does not necessarily ensure the conservation of GD.
Is being familiar with biodiversity related to reasoning about ecology?
Authors: Le Paul T. , Hartley Laurel M. , Doherty Jennifer H. , Harris Cornelia B. , Moore John C.
Published: December 2018

Many science educators believe that student recognition of biodiversity is an important precursor to discovering patterns and understanding processes that define and shape ecological systems. We investigated (1) the total number, taxonomic categories, specificity, and diversity of backyard organisms that middle (MS) and high school (HS) students and teachers named, (2) how the number, specificity, and diversity of organisms that students and teachers named related to their overall performance on an ecology learning progression assessment, and (3) the types of information students used to sort and group organisms. Our sample population included 264 MS students, 374 HS students, and 108 teachers in five U.S. states (California, Colorado, Maryland, Michigan, and New York). We found that students were more likely to name vertebrates than plants or microorganisms, while teachers were more likely to name vertebrate and plants than microorganisms. Teachers named a higher total number (richness) and diversity of organisms and named more organisms in specific (e.g., bull snake) than general taxonomic categories (e.g., snake) than did students. Individual performance on the ecology learning progression assessment was positively correlated to the total number (richness), diversity, and specificity of organisms that students and teachers could name. The types of information students invoked to group organisms together varied by question context. Most students invoked information related to form/outward traits, habitat, function (e.g., decomposer), and taxa (e.g., fungi, plant, animal). Notably, some students invoked ideas about evolutionary relationships among organisms. This work corroborates previous findings about student familiarity with biodiversity and provides preliminary evidence that familiarity with local biodiversity is linked to reasoning about ecology.
Integrated internal standards: A sample prep‐free method for better precision in microchip CE
Authors: Bidulock Allison C.E. , Dubský Pavel , van den Berg Albert , Eijkel Jan C.T.
Published: December 2018

Point‐of‐care systems based on microchip capillary electrophoresis require single‐use, disposable microchips prefilled with all necessary solutions so an untrained operator only needs to apply the sample and perform the analysis. While microchip fabrication can be (and has been) standardized, some manufacturing differences between microchips are unavoidable. To improve analyte precision without increasing device costs or introducing additional error sources, we recently proposed the use of integrated internal standards (ISTDs): ions added to the BGE in small concentrations which form system peaks in the electropherogram that can be used as a measurement reference. Here, we further expand this initial proof‐of‐principle test to study a clinically‐relevant application of K ion concentrations in human blood; however, using a mock blood solution instead of real samples to avoid interference from other obstacles (e.g. cell lysis). Cs as an integrated ISTD improves repeatability of K ion migration times from 6.97% to 0.89% and the linear calibration correlation coefficient (R2) for K quantification from 0.851 to 0.967. Peak area repeatability improves from 11.6–13.3% to 4.75–5.04% at each K concentration above the LOQ. These results further validate the feasibility of using integrated ISTDs to improve imprecision in disposable microchip CE devices by demonstrating their application for physiological samples.
African food insecurity in a changing climate: The roles of science and policy
Authors: Onyutha Charles
Published: December 2018

African population is projected to double to 2.48 billion people by 2050. The population increase poses a serious challenge of increasing food supply to meet the future demand. This challenge is compounded by climate change impacts on agriculture. In this paper, how poverty contributes to household food insecurity is explored and measures suggested to help address this challenge. To plan adaptation measures, linkages among food insecurity, poverty, and illiteracy should be considered. For the sub‐Saharan Africa (SSA), adaptation (focused on poverty alleviation) should be prioritized and preferred to mitigation. Enhancement of adaptive capacity should not only be tailored toward empowerment of women but also made highly localized to household levels. Generally, efforts could be geared toward yield gap closure, addressing challenges regarding food distribution, promoting non‐farm income‐generating activities, and unification of government priorities in agriculture and food security. Government in each country of the SSA should ensure that governance strongly embraces transparency, accountability, and integrity otherwise as it is said a fish rots from the head down. Estimates of uncertainty in predicting future climate and their implications on expenditure related to adaptation should to always be made in an integrated way and reported to support actionable policies. To increase credibility in climate prediction especially at local scales, advances toward improving climate models (for instance by refining spatiotemporal scales, enhancing models’ capacity to reproduce observed natural variability in key climatological variables like rainfall) should be made, and this requires support from the investment in climate science. Science–policy interfacing is required in planning and implementation of measures for adapting to climate change impacts. In summary, food insecurity and persistent poverty especially in the SSA should be of direct relevance and concern at a global scale. Thus, global collaboration in science is key to achieve food security in the SSA.
Dissociation in awareness of memory and language decline in Alzheimer's disease
Authors: Bregman Noa , Kavé Gitit , Shiner Tamara , Biran Iftah ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: December 2018

Objectives

The aim of this study was to examine awareness of decline in memory and in language in individuals with Alzheimer's disease (AD), by comparing participant and informant ratings, as well as these ratings and actual test performance.

Methods

We analyzed data from 149 individuals with AD enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who filled the Everyday Cognition questionnaire and performed memory and language tasks.

Results

Participants provided significantly lower assessments of decline than did informants for both memory and language. There was a negative association between informant ratings and memory test scores but no association between participant ratings and memory test scores. Both participant and informant ratings correlated negatively with performance on the language tests. Informant, but not participant, ratings contributed to the prediction of one memory variable beyond demographic factors. Participant ratings contributed to the prediction of language scores beyond demographic factors more than did informant ratings.

Conclusions

The findings reflect better awareness of decline in language than of decline in memory in individuals with AD.
AHNS series: Do you know your guidelines? Diagnosis and management of salivary gland tumors
Authors: Mantravadi Avinash V. , Moore Michael G. , Rassekh Christopher H.
Published: December 2018

This article is the next installment of the series “Do you know your guidelines” presented by the Education Committee of the American Head and Neck Society. Guidelines for the workup and management of tumors of the major and minor salivary glands are reviewed.
Volumetric 18F‐FDG‐PET parameters as predictors of locoregional failure in low‐risk HPV‐related oropharyngeal cancer after definitive chemoradiation therapy
Authors: Chotchutipan Thong , Rosen Benjamin S. , Hawkins Peter G. , Lee Jae Y. , Saripalli Anjali L. , Thakkar Dharmesh , Eisbruch Avraham , El Naqa Issam , Mierzwa Michelle L.
Published: December 2018

Background

We sought to investigate the prognostic value of volumetric positron emission tomography (PET) parameters in patients with human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) and a ≤10 pack‐year smoking history treated with chemoradiation.

Methods

A total of 142 patients were included. Maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor, involved regional lymph nodes, and total lesion were calculated. Cox proportional hazard modeling was used to evaluate associations of clinical and PET parameters with locoregional failure‐free survival (LRFFS), distant metastasis‐free survival (DMFS), and overall survival (OS).

Results

On univariate analysis, volumetric PET parameters were significantly associated with all endpoints, and 8th edition American Joint Committee on Cancer/Union Internationale Contre le Cancer staging was significantly associated with DMFS and OS. On multivariate analysis, total lesion TLG was significantly associated with LRFFS, while staging was most significantly prognostic for DMFS and OS.

Conclusion

Volumetric PET parameters are uniquely prognostic of LRFFS in low‐risk HPV‐related OPSCC and may be useful for directing de‐intensification strategies.
Alpha‐Fetoprotein Decrease from > 1,000 to < 500 ng/mL in Patients with Hepatocellular Carcinoma Leads to Improved Posttransplant Outcomes
Authors: Mehta Neil , Dodge Jennifer L. , Roberts John P. , Hirose Ryutaro , Yao Francis Y.
Published: December 2018

High alpha‐fetoprotein (AFP) > 1,000 ng/mL is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). A new national policy has been implemented for AFP > 1,000 ng/mL requiring a decrease to < 500 ng/mL before LT, but there is a paucity of data on the optimal AFP threshold before LT. We aimed to evaluate the effects of a reduction in AFP from > 1,000 ng/mL to different AFP thresholds before LT on survival and HCC recurrence after LT using the United Network for Organ Sharing database. We identified 407 patients who underwent transplant between January 2005 and September 2015 and who had AFP > 1,000 ng/mL at least once before LT. The last AFP measurement before LT was > 1,000 ng/mL in 72.0%, decreased from > 1,000 to 101‐499 ng/mL in 9.6%, and decreased to ≤ 100 ng/mL in 14.3%. Local‐regional therapy was not performed in 45.4% of patients with AFP > 1,000 ng/mL at LT versus 12.8% of those with AFP of 101‐499 ng/mL and 10.3% of those with AFP ≤ 100 ng/mL at LT (P < 0.001). Kaplan‐Meier 5‐year post‐LT survival for those with AFP > 1,000 ng/mL at LT was 48.8% versus 67.0% for those with a decrease in AFP to 101‐499 ng/mL (P < 0.001) and 88.4% for those with AFP ≤ 100 ng/mL at LT (P < 0.001). HCC recurrence probability at 5 years was 35.0% for patients with AFP > 1,000 ng/mL versus 13.3% for patients with AFP of 101‐499 ng/mL and 7.2% for patients with AFP ≤ 100 ng/mL at LT (P < 0.001). In multivariable analysis, a decrease in the AFP to 101‐499 ng/mL was associated with a > 2‐fold reduction in posttransplant mortality (P = 0.01) and a nearly 3‐fold reduction in HCC recurrence (P = 0.02) compared with AFP > 1,000 ng/mL at LT. Conclusion: Our results demonstrated significantly improved post‐LT outcomes when restricting LT to patients with a reduction in AFP from > 1,000 to < 500 ng/mL, validating the recently implemented national policy.
Optimal multi‐scale geometric fusion based on non‐subsampled contourlet transform and modified central force optimization
Authors: El‐Hoseny Heba M. , El‐Rahman Wael Abd , El‐Shafai Walid , El‐Rabaie El‐Sayed M. , Mahmoud Korany R. , Abd El‐Samie Fathi E. , Faragallah Osama S.
Published: December 2018

In the current era of technological development, medical imaging plays an important part in several applications of medical diagnosis and therapy. This requires more precise images with much more details and information for correct medical diagnosis and therapy. Medical image fusion is one of the solutions for obtaining much spatial and spectral information in a single image. This article presents an optimization‐based contourlet image fusion approach in addition to a comparative study for the performance of both multi‐resolution and multi‐scale geometric effects on fusion quality. An optimized multi‐scale fusion technique based on the Non‐Subsampled Contourlet Transform (NSCT) using the Modified Central Force Optimization (MCFO) and local contrast enhancement techniques is presented. The first step in the proposed fusion approach is the histogram matching of one of the images to the other to allow the same dynamic range for both images. The NSCT is used after that to decompose the images to be fused into their coefficients. The MCFO technique is used to determine the optimum decomposition level and the optimum gain parameters for the best fusion of coefficients based on certain constraints. Finally, an additional contrast enhancement process is applied on the fused image to enhance its visual quality and reinforce details. The proposed fusion framework is subjectively and objectively evaluated with different fusion quality metrics including average gradient, local contrast, standard deviation (STD), edge intensity, entropy, peak signal‐to‐noise ratio, Q
ab/f, and processing time. Experimental results demonstrate that the proposed optimized NSCT medical image fusion approach based on the MCFO and histogram matching achieves a superior performance with higher image quality, average gradient, edge intensity, STD, better local contrast and entropy, a good quality factor, and much more details in images. These characteristics help for more accurate medical diagnosis in different medical applications.
Secondary structure analysis of peptides with relevance to iron–sulfur cluster nesting
Authors: Hanscam Rebecca , Shepard Eric M. , Broderick Joan B. , Copié Valérie , Szilagyi Robert K.
Published: December 2018

Peptides coordinated to iron–sulfur clusters, referred to as maquettes, represent a synthetic strategy for constructing biomimetic models of iron–sulfur metalloproteins. These maquettes have been successfully employed as building blocks of engineered heme‐containing proteins with electron‐transfer functionality; however, they have yet to be explored in reactivity studies. The concept of iron–sulfur nesting in peptides is a leading hypothesis in Origins‐of‐Life research as a plausible path to bridge the discontinuity between prebiotic chemical transformations and extant enzyme catalysis. Based on past biomimetic and biochemical research, we put forward a mechanism of maquette reconstitution that guides our development of computational tools and methodologies. In this study, we examined a key feature of the first stage of maquette formation, which is the secondary structure of aqueous peptide models using molecular dynamics simulations based on the AMBER99SB empirical force field. We compared and contrasted S…S distances, [2Fe‐2S] and [4Fe‐4S] nests, and peptide conformations via Ramachandran plots for dissolved Cys and Gly amino acids, the CGGCGGC 7‐mer, and the GGCGGGCGGCGGW 16‐mer peptide. Analytical tools were developed for following the evolution of secondary structural features related to [Fe‐S] cluster nesting along 100 ns trajectories. Simulations demonstrated the omnipresence of peptide nests for preformed [2Fe‐2S] clusters; however, [4Fe‐4S] cluster nests were observed only for the 16‐mer peptide with lifetimes of a few nanoseconds. The origin of the [4Fe‐4S] nest and its stability was linked to a “kinked‐ribbon” peptide conformation. Our computational approach lays the foundation for transitioning into subsequent stages of maquette reconstitution, those being the formation of iron ion/iron–sulfur coordinated peptides. © 2018 Wiley Periodicals, Inc.
A note on immersion intertwines of infinite graphs
Authors: Barnes Matthew , Oporowski Bogdan
Published: December 2018

We present a construction of two infinite graphs and , and of an infinite set of graphs such that is an antichain with respect to the immersion relation and, for each graph in , both and are subgraphs of , but no graph properly immersed in admits an immersion of and of . This shows that the class of infinite graphs ordered by the immersion relation does not have the finite intertwine property.
Glycerol Mediated Synthesis, Biological Evaluation, and Molecular Docking Study of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines as Potent Antitubercular Agents
Authors: Jamale Dattatraya K. , Undare Santosh S. , Valekar Navanath J. , Sarkate Aniket P. , Kolekar Govind B. , Anbhule Prashant V.
Published: December 2018

A series of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines were synthesized through one‐pot four‐component Hantzsch condensation of 1,3‐diphenyl‐1H‐pyrazole‐4‐carbaldehydes, ammonium acetate, dimedone, and alkyl acetoacetate in glycerol as a green reaction medium. The structures of the compounds are verified by spectroscopic methods and screened for their antimicrobial activity against Mycobacterium tuberculosis H37RV strain. Almost all the synthesized derivatives reveal excellent antitubercular activity based on minimum inhibitory concentration. Especially the compounds 5h and 5k exhibit outstanding antitubercular activity with minimum inhibitory concentration 1.6 μg/mL. In addition, molecular docking study of synthesized scaffolds against enoyl‐acyl carrier protein reductase from M. tuberculosis was performed to propose the binding modes.
Pyridine‐2(1H)‐thiones: Versatile Precursors for Novel Pyrazolo[3,4‐b]pyridine, Thieno[2,3‐b]pyridines, and Their Fused Azines
Authors: Sanad Sherif M. H. , Abdel‐Fattah Azza M. , Attaby Fawzy A. , Elneairy Mohamed A. A.
Published: December 2018

Pyridine‐2(1H)‐thiones were prepared and reacted with several active halogenated reagents to afford novel thieno[2,3‐b]pyridines in excellent yields. Thieno[2,3‐b]pyridine‐2‐carbohydrazide derivative was prepared by the reaction of either ethyl 2‐((3‐cyanopyridin‐2‐yl)thio)acetate derivative or thieno[2,3‐b]pyridine‐2‐carboxylate derivative with hydrazine hydrate. On the other hand, the reaction of either pyridine‐2(1H)‐thione or ethyl 2‐((pyridin‐2‐yl)thio)acetate derivative with hydrazine hydrate afforded the corresponding 1H‐pyrazolo[3,4‐b]pyridine derivative. Thieno[2,3‐b]pyridine derivatives reacted with several reagents to afford the corresponding pyrimidine‐4(3H)‐ones and [1,2,3]triazin‐4‐(3H)‐one. Moreover, 2‐carbohydrazide derivative reacted with β‐dicarbonyl reagents to give 2‐((3‐methyl‐1H‐pyrazol‐1‐yl)carbonyl)thienopyridines. The structure of the target molecules is elucidated using elemental analyses and spectral data.
Mortality and losses to follow‐up among adolescents living with HIV in the IeDEA global cohort collaboration
Authors: Kariminia Azar , Law Matthew , Davies Mary‐Ann , Vinikoor Michael , Wools‐Kaloustian Kara , Leroy Valeriane , Edmonds Andrew , McGowan Catherine , Vreeman Rachel , Fairlie Lee , Ayaya Samuel , Yotebieng Marcel , Takassi Elom , Pinto Jorge , Adedimeji Adebola , Malateste Karen , Machado Daisy M , Penazzato Martina , Hazra Rohan , Sohn Annette H ,   on behalf of IeDEA
Published: December 2018

Introduction

We assessed mortality and losses to follow‐up (LTFU) during adolescence in routine care settings in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

Methods

Cohorts in the Asia‐Pacific, the Caribbean, Central, and South America, and sub‐Saharan Africa (Central, East, Southern, West) contributed data, and included adolescents living with HIV (ALHIV) enrolled from January 2003 and aged 10 to 19 years (period of adolescence) while under care up to database closure (June 2016). Follow‐up started at age 10 years or the first clinic visit, whichever was later. Entering care at <15 years was a proxy for perinatal infection, while entering care ≥15 years represented infection acquired during adolescence. Competing risk regression was used to assess associations with death and LTFU among those ever receiving triple‐drug antiretroviral therapy (triple‐ART).

Results

Of the 61,242 ALHIV from 270 clinics in 34 countries included in the analysis, 69% (n = 42,138) entered care <15 years of age (53% female), and 31% (n = 19,104) entered care ≥15 years (81% female). During adolescence, 3.9% died, 30% were LTFU and 8.1% were transferred. For those with infection acquired perinatally versus during adolescence, the four‐year cumulative incidences of mortality were 3.9% versus 5.4% and of LTFU were 26% versus 69% respectively (both p < 0.001). Overall, there were higher hazards of death for females (adjusted sub‐hazard ratio (asHR) 1.19, 95% confidence interval (CI) 1.07 to 1.33), and those starting treatment at ≥5 years of age (highest asHR for age ≥15: 8.72, 95% CI 5.85 to 13.02), and in care in mostly urban (asHR 1.40, 95% CI 1.13 to 1.75) and mostly rural settings (asHR 1.39, 95% CI 1.03 to 1.87) compared to urban settings. Overall, higher hazards of LTFU were observed among females (asHR 1.12, 95% CI 1.07 to 1.17), and those starting treatment at age ≥5 years (highest asHR for age ≥15: 11.11, 95% CI 9.86 to 12.53), in care at district hospitals (asHR 1.27, 95% CI 1.18 to 1.37) or in rural settings (asHR 1.21, 95% CI 1.13 to 1.29), and starting triple‐ART after 2006 (highest asHR for 2011 to 2016 1.84, 95% CI 1.71 to 1.99).

Conclusions

Both mortality and LTFU were worse among those entering care at ≥15 years. ALHIV should be evaluated apart from younger children and adults to identify population‐specific reasons for death and LTFU.
Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity
Authors: Puyo Carlos A , Earhart Alexander , Staten Nicholas , Prince Oliver A , Haug Colleen , Kollef Marin , Awad Michael
Published: December 2018

Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF-κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N-acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF-κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF-κB dependent activity was confirmed by HEK-Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF-κB activity may have benefits in prevention of acute tracheal damage.
Influence of reduced tip‐apex distance on helical blade fixation—a biomechanical study
Authors: Lenz Mark , Schwinn Jana , Hofmann‐Fliri Ladina , Schwyn Ronald , Knobe Matthias , Klos Kajetan , Kielstein Heike , Hofmann Gunther O. , Gueorguiev Boyko
Published: December 2018

Migration profile of helical blades differs from conventional screw design. Tip‐apex distance (TAD) greater than 25 mm is associated with early failure in hip screws. This study investigates the effect of a reduced TAD on helical blade fixation. Six pairs of human femoral heads were used. Bone mineral density (BMD) was determined by pQCT. Local bone quality was evaluated by breakaway torque. Helical blades were implanted with TAD of 20 mm (normal) and 6 mm (reduced). Specimens were cyclically tested under progressively increasing physiologic loading at 2 Hz with starting peak force of 1′000N, increasing by 0.1N/cycle. Implant migration was monitored by radiographs every 250 cycles. Paired Student's t‐test and Spearman rank correlation coefficient were used for statistical evaluation (p < 0.05). Mean BMD was 246.7 mgHA/cm3 SD48.7 (normal), 244.3 mgHA/cm3 SD47.6 (reduced); p = 0.93. Mean breakaway torque was 3.59 Nm SD2.11 (normal), 3.72 Nm SD1.83 (reduced); p = 0.91. Number of cycles to failure (1 mm vertical migration) was 16′416 SD7972 (normal), 20′000 SD5232 (reduced); p = 0.38. They correlated significantly with BMD (p = 0.01;R2 = 0.91) and breakaway torque (p < 0.049; R2 = 0.814) (normal). Breakaway torque correlated significantly with BMD (p = 0.02; R2 = 0.898) (normal). In reduced TAD these parameters did not correlate significantly. Normal TAD resulted in failure in varus collapse (n = 6), whereas reduced TAD showed blade perforation (n = 3), rotation (n = 2), varus collapse (n = 1). Fixation stability of helical blades correlates with bone quality when implants are fixed in cancellous bone. Near cortical blade fixation might increase the risk of intraarticular blade perforation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–6, 2019.