bluuebunny/crossref_metadata_2025 huggingface dataset:
Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV‐1 Transcription in a Phase IIb Trial
Authors: Lee Sulggi A. , Elliott Julian H. , McMahon James , Hartogenesis Wendy , Bumpus Namandje N. , Lifson Jeffrey D. , Gorelick Robert J. , Bacchetti Peter , Deeks Steven G. , Lewin Sharon R. , Savic Radojka M.
Published: August 2018

Disulfiram (DSF) was well tolerated and activated viral transcription (cell‐associated unspliced (CA‐US) and plasma human immunodeficiency virus (HIV) RNA) in a phase II dose‐escalation trial in HIV+ antiretroviral therapy (ART)‐suppressed participants. Here, we investigated whether exposure to DSF and its metabolites predicted these changes in HIV transcription. Participants were administered 500 (N = 10), 1,000 (N = 10), or 2,000 (N = 10) mg of DSF for 3 consecutive days. DSF and four metabolites were measured by ultraperformance liquid chromatography‐tandem mass spectrometry. Changes in CA‐US and plasma HIV RNA were quantified by polymerase chain reaction (PCR) and analyzed in NONMEM. A seven‐compartment pharmacokinetic (PK) model demonstrated nonlinear elimination kinetics. The fitted median area under the curve values for 72 hours (AUC0–72) were 3,816, 8,386, and 22,331 mg*hour/L, respectively. Higher exposure predicted greater increases in CA‐US (maximum effect (Emax) = 78%, AUC50 = 1,600 μg*hour/L, P = 0.013) but not plasma HIV RNA. These results provide support for further development of DSF as an important drug for future HIV cure strategies.
Pharmaco‐resistant Neonatal Seizures: Critical Mechanistic Insights from a Chemoconvulsant Model
Authors: Kharod Shivani C. , Carter Brandon M. , Kadam Shilpa D.
Published: August 2018

Neonatal seizures are harmful to the developing brain and are associated with mortality and long‐term neurological comorbidities. Hypoxic‐ischemic encephalopathy (HIE) seizures represent a significant proportion of such seizures. Phenobarbital (PB) remains the first line anti‐seizure drug (ASD) treatment but fails ~50% of the time. Translational models of neonatal seizures are crucial to investigating mechanisms underlying PB‐resistance. A model of PB‐resistant ischemic seizures in postnatal day 7 (P7) CD‐1 mice reported K‐Cl cotransporter 2 (KCC2) degradation that has been shown to be due to activation of the TrkB pathway. We investigated PB‐efficacy in a pentylenetetrazole (PTZ) model of neonatal seizures in the same strain and age using identical treatment protocols to gain insights into mechanisms underlying PB‐resistance. A single dose of PTZ (80 mg/kg; IP) consistently induced repetitive seizures that did not progress to status epilepticus (SE). PB (25 mg/kg; IP, single dose) significantly suppressed the PTZ‐induced seizures. This was associated with significant KCC2 upregulation and stable Na‐K‐Cl cotransporter 1 (NKCC1) expression at 24h. The TrkB pathway was not activated. PTZ seizure burdens were significantly higher than those reported for ischemic seizures, indicating seizure severity did not dictate the differences in PB‐efficacy. Bumetanide (BTN) (0.1–0.2 mg/kg; IP) did not work as an anti‐seizure agent, similar to the ischemic model. When investigating mechanisms underlying the emergence of PB‐resistance in translational models, the method by which seizures are induced may dictate mechanisms underlying emergence of PB‐resistance.
Effectiveness of camera traps for quantifying daytime and nighttime visitation by vertebrate pollinators
Authors: Krauss Siegfried L. , Roberts David G. , Phillips Ryan D. , Edwards Caroline
Published: August 2018

Identification of pollen vectors is a fundamental objective of pollination biology. The foraging and social behavior of these pollinators has profound effects on plant mating, making quantification of their behavior critical for understanding the ecological and evolutionary consequences of different pollinators for the plants they visit. However, accurate quantification of visitation may be problematic, especially for shy animals and/or when the temporal and spatial scale of observation desired is large. Sophisticated heat‐ and movement‐triggered motion‐sensor cameras (“camera trapping”) provide new, underutilized tools to address these challenges. However, to date, there has been no rigorous evaluation of the sampling considerations needed for using camera trapping in pollination research.

We measured the effectiveness of camera trapping for identifying vertebrate visitors and quantifying their visitation rates and foraging behavior onBanksia menziesii(Proteaceae). Multiple still cameras (Reconyx HC 500) and a video camera (Little Acorn LTL5210A) were deployed.

From 2,753 recorded visits by vertebrates, we identified five species of nectarivorous honeyeater (Meliphagidae) and the honey possum (Tarsipedidae), with significant variation in the species composition of visitors among inflorescences. Species of floral visitor showed significant variation in their time of peak activity, duration of visits, and numbers of flowers probed per visit. Where multiple cameras were deployed on individual inflorescences, effectiveness of individual still cameras varied from 15% to 86% of all recorded visits. Methodological issues and solutions, and the future uses of camera traps in pollination biology, are discussed.

Conclusions and wider implications: Motion‐triggered cameras are promising tools for the quantification of vertebrate visitation and some aspects of behavior on flowers. However, researchers need to be mindful of the variation in effectiveness of individual camera traps in detecting animals. Pollinator studies using camera traps are in their infancy, and the full potential of this developing technology is yet to be realized.
Integrated extrusion‐enzymatic treatment of corn bran for production of functional cake
Authors: Haghighi‐Manesh Soroush , Azizi Mohammad Hossein
Published: August 2018

Corn bran, as one of the high‐fructose corn syrup industries’ by‐products, is a rich source of functional fibers. The major fraction of corn bran is insoluble arabinoxylan having lower functional properties than the minor soluble function. Therefore, the main aim of this research was to increase the soluble fiber content of corn bran and use it for functional cake production. In this regard, milled corn bran with three different sizes was exposed to one factor enzymatic treatment to select the best sieving size (the criterion for selecting the best product in each stage of assay was production of the highest amount of soluble fiber). Then, milled corn bran with the best particle size was exposed to nine different enzymatic treatments to select the best enzymatic treatment condition. Additionally, the extruder feed (corn bran) moisture was adjusted to three levels to select the best level of feed moisture content and use it for performing nine different extruding experiments. Concerning integrated extrusion‐enzymatic treatment, nine different extruding pretreatments were conducted on corn bran through selecting the optimum moisture level of extruding. Afterward, the product was milled and sieved to the optimum size for enzymatic treatment, and the nine pretreatments were combined with nine different enzymatic treatments. The product containing the highest soluble fiber was selected and used at various levels for functional cake production. Finally, some organoleptic and physicochemical properties (springiness, gumminess, hardness, cohesiveness, Bostwick number, density) of the produced product were analyzed.
Structural and functional changes of the visual cortex in early Huntington's disease
Authors: Coppen Emma M. , Grond Jeroen van der , Hafkemeijer Anne , Barkey Wolf Jurriaan J. H. , Roos Raymund A. C.
Published: August 2018

Huntington's disease (HD) is an autosomal‐dominant inherited neurodegenerative disorder characterized by motor disturbances, psychiatric disturbances, and cognitive impairment. Visual cognitive deficits and atrophy of the posterior cerebral cortex are additionally present in early disease stages. This study aimed to assess the extent of structural and functional brain alterations of the visual cortex in HD gene carriers using different neuroimaging modalities. Structural and functional magnetic resonance imaging data were acquired from 18 healthy controls, 21 premanifest, and 20 manifest HD gene carriers. Voxel‐based morphometry (VBM) analysis and cortical thickness measurements were performed to assess structural changes in the visual cortex. Brain function was measured by assessing neuronal connectivity changes in response to visual stimulation and at rest in visual resting‐state networks. Multiple linear regression analyses were performed to examine the relationship between visual cognitive function and structural imaging measures. Compared to controls, pronounced atrophy and decreased neuronal function at rest were present in associative visual cortices in manifest HD. The primary visual cortex did not show group differences in cortical thickness and in vascular activity after visual stimulation. Thinning of the associative visual cortex was related to worse visual perceptual function. Premanifest HD gene carriers did not show any differences in brain structure or function compared to controls. This study improves the knowledge on posterior brain changes in HD, as our findings suggest that the primary visual cortex remains preserved, both structurally and functionally, while atrophy of associative visual cortices is present in early HD and linked to clinical visual deficits.
Making HPV vaccination available to girls everywhere
Authors: Oberlin Austin M. , Rahangdale Lisa , Chinula Lameck , Fuseini Nurain M. , Chibwesha Carla J.
Published: August 2018

Cervical cancer is currently the fourth leading cause of cancer death among women worldwide, with most cases occurring in low‐ and middle‐income countries. Safe, highly effective vaccines against HPV have been on the market since 2006, yet only 6% of girls worldwide have received this life‐saving cancer prevention intervention. International organizations, including PATH, Gavi, and the pharmaceutical companies Merck and GlaxoSmithKline, have provided support to eligible low‐ and middle‐income countries to implement national HPV vaccination programs. Still, glaring disparities in the availability of national HPV vaccination programs and the coverage of the primary target population between the global north and south persist. We illustrate worldwide HPV vaccine implementation and coverage using an online data visualization, which is publicly available and can be used to gain unique insights. We also present three emerging solutions to transform future HPV vaccine delivery in low‐ and middle‐income countries: low‐cost generics, single‐dose vaccination, and co‐administration with other adolescent vaccines. By rapidly expanding access to HPV vaccination to girls everywhere, vaccine‐type HPV infections can be virtually eliminated. At high vaccination‐coverage levels, more than 80%—or approximately 230 000—of the cervical cancer deaths that occur each year can be averted.
Coherent Raman spectroscopic imaging to characterize microglia activation pathway
Authors: Dessai Chinmayee V. P. , Pliss Artem , Kuzmin Andrey N. , Furlani Edward P. , Prasad Paras N.
Published: August 2018

Microglia are immune cells, which densely populate the central nervous system (CNS), and play essential role in suppression of neurodegenerative diseases, clearance of debris after CNS trauma, as well as serve as the last line of immune defense in response to any potential threat by being activated to eliminate diverse pathogens ranging from bacteria to cancer. The activated microglia cells are commonly used as a diagnostic biomarker of diverse brain conditions, however detection and classification of microglia activated phenotypes is a cumbersome and imprecise procedure. Here, we report on development of optical assay for detection and quantitative analysis of activated microglia. In this study, we investigated overall changes in the metabolism of microglia cells during their activation by monitoring the signal from cellular proteins and lipids using label‐free coherent anti‐Stokes Raman scattering imaging. Our data demonstrate that the activation of microglia in the presence of bacterial liposaccharide is accompanied by intense upregulation of synthesis of proteins and lipids. We further propose that elevated intracellular content of these types of macromolecules can serve as early supplementary marker for identification of active microglia cells in the brain samples by Raman imaging techniques.
Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations
Authors: Jha Smita , Fratzl-Zelman Nadja , Roschger Paul , Papadakis Georgios Z , Cowen Edward W , Kang Heeseog , Lehky Tanya J , Alter Katharine , Deng Zuoming , Ivovic Aleksandra , Flynn Lauren , Reynolds James C , Dasgupta Abhijit , Miettinen Markku , Lange Eileen , Katz James , Klaushofer Klaus , Marini Joan C , Siegel Richard M , Bhattacharyya Timothy
Published: August 2018

Melorheostosis is a rare hyperostotic disease of the long bones classically characterized by a “dripping candle-wax” radiographic appearance. We recently described somatic activating mutations in MAP2K1 as a cause of melorheostosis. Here, we report distinguishing characteristics of patients with MAP2K1-positive melorheostosis. Fifteen unrelated patients with radiographic appearance of melorheostosis underwent paired biopsies of affected and unaffected bone for whole-exome sequencing, histology, and cell culture. Eight patients with mutations in MAP2K1 in affected bone were compared to the seven MAP2K1-negative patients to identify distinguishing characteristics. Patients with MAP2K1-positive melorheostosis had a distinct phenotype with classic “dripping candle-wax” appearance on radiographs (p = 0.01), characteristic vascular lesions on skin overlying affected bone (p = 0.01), and higher prevalence of extraosseous mineralization and joint involvement (p = 0.04 for both). Melorheostotic bone from both MAP2K1-positive and MAP2K1-negative patients showed two zones of distinct morphology—an outer segment of parallel layers of primary lamellar bone and a deeper zone of intensely remodeled highly porous osteonal-like bone. Affected bone from MAP2K1-positive patients showed excessive osteoid (p = 0.0012), increased number of osteoblasts (p = 0.012) and osteoclasts (p = 0.04), and increased vascularity on histology in comparison to paired unaffected bone which was not seen in affected bone in most MAP2K1-negative patients. The identification of a distinct phenotype of patients with MAP2K1-positive melorheostosis demonstrates clinical and genetic heterogeneity among patients with the disease. Further studies are needed to better understand the underlying pathophysiology and associated skin findings. © 2018 American Society for Bone and Mineral Research.

Abstract

Patients with melorheostosis associated with somatic mosaic MAP2K1 mutations (found in affected bone and skin overlying affected bone) were more likely to have cutaneous vascular changes in skin overlying affected bone, classic “dripping candle-wax appearance” on x-rays and increased osteoid on bone histomorphometry. Presence of these characteristics may predict association with MAP2K1 mutations.
Theoretical investigation of the catalytic effect of microingredients on ammonium perchlorate (AP) thermal decomposition
Authors: Liu Min‐Hsien , Liu Chuan‐Wen , Tsai Hou‐Jen
Published: August 2018

This study employed quantum chemical modeling to explore the low‐temperature (i.e., below 300 °C) decomposition of ammonium perchlorate (AP) in terms of the reaction mechanisms, analyzing the kinetics of decomposition in gaseous noncatalyzed and catalyzed systems. Based upon transition‐state theory, the calculated rate constant together with the initial partial pressure of the reaction species were included in the integrated form into the rate law of the elementary reaction to compute the half‐life of AP decomposition and further evaluate the corresponding lifetime of the stored material. The results of this study revealed that upon increasing the reaction temperature, the stepwise decrease in the activation barrier and the stepwise increase in the rate constant of AP decomposition exhibited expected trends. In addition, via proton transfer and bond‐cleavage mechanisms, ammonium chlorate exerted a positive catalytic effect that showed decomposition is unfavorable. However, ammonium dihydrogen phosphate and ammonium halide exhibited negative catalytic effects that slowed decomposition, and both of them may be incorporated into AP composite propellants to prolong their shelf life. The use of these stabilizing catalysts is estimated to increase the relative lifetime of materials under storage by two orders of magnitude, potentially benefiting ammunition storage.
Effects of a State‐ and Use‐Dependent Nav1.7 Channel Blocker on Ambulatory Blood Pressure: A Randomized, Controlled Crossover Study
Authors: Fong Regan , Ballow Charles H. , Naik Himanshu , Steiner Deb , Palmer Joanne , White William B.
Published: August 2018

Vixotrigine is a state‐ and use‐dependent Nav1.7 channel blocker being investigated for the treatment of neuropathic pain conditions. This randomized, double‐blind, placebo‐controlled crossover trial was designed to evaluate changes in blood pressure with the administration of vixotrigine using ambulatory blood pressure monitoring (ABPM). Eligible participants were healthy adults 18 to 65 years of age without evidence of baseline systolic blood pressure (SBP) persistently > 140 mm Hg or diastolic blood pressure (DBP) persistently > 90 mm Hg. Vixotrigine (400 mg [men], 300 mg [women]) or placebo was administered orally twice daily for 36 days. Following a 7‐day washout period, participants crossed over to the other treatment. Each dosing period was preceded by 1 inpatient visit and 1 outpatient baseline visit. Two 14‐hour inpatient ABPM sessions occurred on days 14 and 35, with a return to the clinic the morning of days 15 and 36 for initiation of outpatient ABPM, which assessed blood pressure and heart rate every 15 minutes. Adverse events were collected throughout the study. The primary end point was the change from baseline in 24‐hour mean SBP and DBP on day 36. Sixty participants were enrolled; 10 withdrew from the study owing to adverse events, investigator discretion, or withdrawal of consent. From baseline to day 36, mean changes in average SBP and DBP (vixotrigine treated) were ‐0.33 and 0.20 mm Hg, respectively. Adverse event rates were comparable for vixotrigine and placebo; the most common adverse events were headache, dizziness, and nausea. Vixotrigine administration is not associated with a clinically important increase in blood pressure.
Extreme value analysis and forecasting of maximum precipitation amounts in the western Black Sea subregion of Turkey
Authors: Yozgatlıgil Ceylan , Türkeş Murat
Published: August 2018

Monthly maximum precipitation amounts for the period 1950–2010 were modelled for seven climatological stations in the western Black Sea subregion of Turkey using a distributional and time series analysis approach. First, the generalized extreme value (GEV) distribution was fitted using the location parameter of the GEV distribution as a function of several explanatory variables that affect the maximum precipitation. We quantified the change in extreme precipitation for each location and derived estimates of return levels for monthly precipitation amounts. We also considered a multivariate time series model with exogenous variables using the selected locations for a short‐term forecast of the maximum precipitation amount. It was discovered that the time series model that takes into account the autocorrelation structure of the series performed better than a probabilistic approach using the extreme value theory. The obtained forecast results are promising in terms of accurately defining future precipitation amounts.
Northeast United States growing season moisture conditions: Associations with a North American mid‐tropospheric wave train
Authors: Suriano Zachary J. , Benjamin Andrew E. , Leathers Daniel J. , Schroeter Derek , Corradina Victoria
Published: August 2018

The Palmer Drought Severity Index is examined in the Northeast United States during the May–September growing seasons of 1950–2016, seeking to better understand the role of atmospheric circulation in moisture variability. Moist conditions for the Northeast are associated with the development of a mid‐tropospheric wave train over the United States, with enhanced ridging over the west, a trough over the Ohio Valley, and ridging over the Atlantic Ocean east of Newfoundland that favours enhanced uplift, precipitation, and southeasterly flow at the surface in the Northeast. A scalar representation of the wave train, a Summer Atmospheric Drought Index (SADI), is developed and robustly validated as a strong indicator of the Northeast moisture conditions. The SADI mid‐tropospheric wave train is the second largest mode of 500 hPa height variability over the North American sector from 1950–2016, and has an increasing trend such that the ridge‐trough‐ridge pattern is more prevalent and/or has become more enhanced with time. The wave train pattern has a significant and positive relationship to the phases of the Arctic Oscillation (AO) and North Atlantic Oscillation (NAO). This indicates that when the AO and NAO indices are positive, the wave train pattern favours the ridge‐trough‐ridge configuration over North America, and can lead to moist conditions in the Northeast. The opposite pathway is also valid and can lead to dry conditions in the Northeast. This pathway provides a physical link between Northeast moisture conditions and global‐scale variability, improving the understanding of atmospheric influences on regional drought and excessive moisture conditions.
A comprehensive analysis of hail events in Portugal: Climatology and consistency with atmospheric circulation
Authors: Santos João A. , Belo‐Pereira Margarida
Published: August 2018

A first hail climatology in mainland Portugal is provided, based on a network of 15 meteorological stations and over the period of 1971–2009 (39 years). Three hail sub‐classes based on the SYNOP codes were considered (small hail, hail without thunder and hail with thunder). Furthermore, hail occurrences were also compared with thunderstorm, convection and precipitation days. Hail events are more frequent in northern Portugal during winter and spring (peaking in April). Both thunderstorm and convection events present a maximum in April–May and a secondary peak in autumn (October). This secondary peak is frequently associated with convective storms without hailfall at the ground, as no clear autumnal maximum is recorded in the hail frequency, particularly in the case of small hail and hail without thunder. The typically higher temperatures in October than in February–April may lead to excessively high‐freezing level heights that hamper hailfall at the surface. The dynamical mechanisms underlying hail occurrence in mainland Portugal were also analysed using eight three‐dimensional weather types. The atmospheric conditions associated with three weather types: Western European Trough, Blocking and Scandinavian Trough were responsible for ca. 75% of the hail events throughout Portugal. Overall, hail events are favoured either by extra‐tropical depressions, with cold front passages over Portugal, or by upper‐level troughs/lows over western Iberia, but preferably occurring in the period from December to May. These dynamical drivers promote instability conditions, which were also diagnosed by the convective available potential energy and total‐totals index.
The effects of different frying oils on the formation of heterocyclic aromatic amines in meatballs and the changes in fatty acid compositions of meatballs and frying oils
Authors: Ekiz Elif , Oz Fatih
Published: August 2018

BACKGROUND

The effects of different frying oils (sunflower, hazelnut, canola, commercially mixed, corn, riviera olive, and natural extra virgin olive) on the formation of heterocyclic aromatic amines (HCAs) in meatballs, and the changes in fatty acid composition of meatballs and frying oils before and after deep‐fat frying, were determined.

RESULTS

Frying oils had a very significant effect (P < 0.01) on fatty acid composition and the total HCA content of meatballs. It was determined, in meat, intermuscular fat, meatballs, and all of the different frying oils, that the most common saturated fatty acids (SFAs) were palmitic acid and stearic acid, the most common monounsaturated fatty acid (MUFA) was oleic acid, and the most common polyunsaturated fatty acid (PUFA) was linoleic acid. Only 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) was detected in deep‐fat fried meatballs, whereas other HCAs (2‐amino‐3‐methylimidazo[4,5‐f]quinoxaline (IQx), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ), 2‐amino‐3,4‐dimethylimidazo[4,5‐f]quinoline (MeIQ), 2‐amino‐3,7,8‐trimethylimidazo[4,5‐f]quinoxaline (7,8‐DiMeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline (4,8‐DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 2‐amino‐9H‐pyrido[2,3‐b]indole (AαC) and 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole (MeAαC)) could not be detected. The total amount of HCAs in the meatballs ranged between 30.43 and 43.71 ng g−1.

CONCLUSION

The results of the present study showed that MeIQx could be formed in deep‐fat fried meatballs with different frying oils. The lowest MeIQx content was found in meatballs fried in hazelnut oil and the highest MeIQx content was found in meatballs fried in commercially mixed oil. © 2018 Society of Chemical Industry
Impact of agronomic practices on grape aroma composition: a review
Authors: Alem Hubert , Rigou Peggy , Schneider Rémi , Ojeda Hernán , Torregrosa Laurent
Published: August 2018

Aroma compounds are secondary metabolites that play a key role in grape quality for enological purposes. Terpenes, C13‐norisoprenoids, phenols, and non‐terpenic alcohols are the most important aroma compounds in grapes and they can be found as free volatiles or glycoconjugated (bound) molecules. The non‐volatile glycosylated group is the largest, and it is present in all varieties of Vitis vinifera (L.), the most widely used species for wine production. These aroma precursors represent the reserve of aroma molecules that can be released during winemaking. Their relative and absolute concentrations at fruit ripening determine the organoleptic value of the final product. A large range of biotic and abiotic factors can influence their biosynthesis in several ways. Agronomic practices such as irrigation, training systems, leaf removal, and bunch thinning can have an effect at plant level. The spraying of stimulatory compounds on fruit at different developmental stages has also been shown to modify metabolic pathways at fruit level with some impact on the aroma composition of the grapevine fruit. Viticulturists could act to promote aroma precursors to improve the aromatic profile of grapes and the wine ultimately produced. However, agronomic practices do not always have uniform results. The metabolic and physiological changes resulting from agronomic practices are unknown because there has not been sufficient research to date. This review presents the state of the art regarding the influences of vineyard agronomic management on the biosynthesis of grape aroma compounds. Although literature regarding the topic is abundant there are still many unknown biological mechanisms involved and/or that have been insufficiently studied. The aim of this work is therefore to find the gaps in scientific literature so that future investigations can focus on them. © 2018 Society of Chemical Industry
Salt‐stress induced proteomic changes of two contrasting alfalfa cultivars during germination stage
Authors: Gao Yanli , Cui Yanjun , Long Ruicai , Sun Yan , Zhang Tiejun , Yang Qingchuan , Kang Junmei
Published: August 2018

BACKGROUND

Alfalfa (Medicago sativa L.), the primary forage crop throughout the world, is sensitive to salt stress during the germination stage. To investigate the response of alfalfa to salt stress, a comprehensive proteomic analysis was performed comparing alfalfa cultivars that differ in salinity tolerance in the early seedling.

RESULTS

Five cultivars were examined for salt tolerance, and the most salt‐tolerant cultivar, ZhongmuNo.3, and the most salt‐sensitive cultivar, Daxiyang, were compared in terms of their physiological and proteomic responses. The two alfalfa cultivars seeds were exposed to 0 mmolL−1 or 200 mmolL−1 NaCl salt treatment for 10 days. Salt stress significantly reduced young seedling growth and the cotyledons' chlorophyll content; meanwhile, it increased the cotyledons' H2O2 and malondialdehyde (MDA) levels, all of which were less adversely affected in ZhongmuNo.3 than in Daxiyang. A total of 51 spots (24 and 27 protein spots in the salt‐sensitive and salt‐tolerant cultivars, respectively) were identified as significantly differentially expressed using two‐dimensional electrophoresis analysis. The proteins that were associated with salt tolerance included antioxidants/detoxifying enzymes, molecular chaperones, energy metabolic enzymes, a secondary metabolic enzyme, and pathogenesis‐related proteins.

CONCLUSIONS

Under salt stress, ZhongmuNo.3 possessed a higher capacity for reactive oxygen species (ROS) scavenging, a more abundant energy supply, and stronger photosynthesis than the salt‐sensitive cultivar Daxiyang, and these physiological processes may be the primary contributors to salt tolerance in ZhongmuNo.3. These advanced proteome data expand our knowledge of the physiology of the response of alfalfa to salt stress, providing a potentially valuable foundation for molecular breeding to enhance salt tolerance. © 2018 Society of Chemical Industry
Enzymatic validation of species‐specific protocols for metal subcellular fractionation in freshwater animals
Authors: Cardon Pierre‐Yves , Caron Antoine , Rosabal Maikel , Fortin Claude , Amyot Marc
Published: August 2018

The use of fractionation protocols to determine metal subcellular distribution in aquatic organisms has gained much interest over the last 15 yr, however, accurate separations among the different components of cells are challenging. Subcellular fractions separated with such an approach are operationally defined and a potentially significant difference can exist between anticipated and resulting fractions. This study customizes and validates subcellular partitioning protocols, for three different freshwater organisms representing a diversity of challenges for subcellular fractionation:Daphnia magna,Chironomus riparius, and liver ofOncorhynchus mykiss. Several protocols involving different homogenization methods, centrifugation speeds, or conservation conditions were tested, and their efficiencies were assessed using enzymatic biomarker assays. Our work allowed us to identify critical steps to improve separations. First, forD. magna, a crustacean with a reinforced chitinous exoskeleton, the use of a strong homogenization method using a sonicator is necessary. Second, for both invertebrates, we observed the leaking of the mitochondrial matrix during cell fractionation, regardless of the homogenization strength and conservation conditions. Therefore, we propose that the mitochondria fraction should be referred to as the mitochondrial membrane fraction, and the cytosol fraction should be identified as the cytosol and mitochondrial matrix fraction. Third, the presence of a lipid‐rich layer duringO. mykissliver fractionation may lead to an overlap between mitochondria and cytosol and must be considered in the protocol development. Finally, lysosomes should not be pooled with the microsomes fraction without prior validation. Overall, this study provides a benchmark for future methodological studies on similar taxa.
A support vector machine‐based ensemble algorithm for pitting corrosion modeling of EN 1.4404 stainless steel in sodium chloride solutions
Authors: Jiménez‐Come María Jesús , de la Luz Martín María , Matres Victoria
Published: August 2018

The resistance to localized corrosion of stainless steel in sodium chloride solutions is evaluated at different conditions. The effects of chloride ion concentration, acidity, and temperature on pitting corrosion resistance are analyzed. In order to develop a model capable of predicting pitting corrosion behavior of EN 1.4404 by an automatic way, a support vector machine‐based ensemble algorithm is proposed. An additional step related to feature selection is included in the model in order to improve the prediction capability. According to the excellent prediction results, the support vector machines (SVM) model is used to perform a sensitivity analysis for the purpose of analyzing the influence of the environmental variables on the breakdown potential and the pitting corrosion status modeling of this grade of stainless steel. Based on this analysis, it can be concluded that the breakdown potential is the main variable to be considered in pitting corrosion modeling whereas temperature is the most important one for breakdown potential modeling.
Ultradifferential operators in the study of Gevrey solvability and regularity
Authors: Ragognette Luis F.
Published: August 2018

In this work we present a new representation formula for ultradistributions using the so‐called ultradifferential operators. The main difference between our representation result and other works is that here we do not break the duality of Gevrey functions of other s and their ultradistributions, i.e., we locally represent an element of by an infinite order operator acting on a function of class . Our main application was in the local solvability of the differential complex associated to a locally integrable structure in a Gevrey environment.
DNA mismatch repair activity of MutLα is regulated by CK2‐dependent phosphorylation of MLH1 (S477)
Authors: Weßbecher Isabel M. , Hinrichsen Inga , Funke Sebastian , Oellerich Thomas , Plotz Guido , Zeuzem Stefan , Grus Franz H. , Biondi Ricardo M. , Brieger Angela
Published: August 2018

MutLα, a heterodimer consisting of MLH1 and PMS2, is a key player of DNA mismatch repair (MMR), yet little is known about its regulation. In this study, we used mass spectrometry to identify phosphorylated residues within MLH1 and PMS2. The most frequently detected phosphorylated amino acid was serine 477 of MLH1. Pharmacological treatment indicates‎ that Casein kinase II (CK2) could be responsible for the phosphorylation of MLH1 at serine 477 in vivo. In vitro kinase assay verified MLH1 as a substrate of CK2. Most importantly, using in vitro MMR assay we could demonstrate that p‐MLH1S477 lost MMR activity. Moreover, we found that levels of p‐MLH1S477 varied during the cell cycle. In summary, we identified that phosphorylation of MLH1 by CK2 at amino acid position 477 can switch off MMR activity in vitro. Since CK2 is overexpressed in many tumors and is able to inactivate MMR, the new mechanism here described could have an important impact on tumors overactive in CK2.
Evaluation of perfusion by near‐infrared fluorescence imaging in late pedicle obstruction of a parascapular flap to the lower extremity: A case report
Authors: Strübing Felix F. , Bigdeli Amir K. , Schmidt Volker J. , Maraka Spyridoula , Kneser Ulrich , Kotsougiani Dimitra
Published: August 2018

Late free flap failures due to pedicle obstruction are rare adverse events. The purpose of this report is to present a case in which the near‐infrared indocyanine green video angiography (ICG‐NIR‐VA) was used to evaluate the perfusion in a compromised fasciocutaneous flap in the late postoperative period. A 55‐year‐old male patient, who initially suffered from an open tibial fracture, developed concurrent osteomyelitis with fistulae of the proximal tibia requiring excision. Reconstruction was achieved using a parascapular flap of 25 × 8 cm, anastomosed to an arterio–venous (AV) Loop in the adductor canal. On the 2nd postoperative day the patient developed a thrombosis of the AV‐Loop. After thrombectomy, the postoperative course was uneventful. Seven weeks postoperatively the patient presented with a mottled, partially bluish and cold flap. Anticoagulation prophylaxis was stopped 2 days earlier. Angiography confirmed a thrombus in the arterial pedicle leading to flap ischemia. Near infrared guided fluorescence imaging revealed a delayed recapillarization of the proximal part of the flap closest to the vascular pedicle, albeit flap overall perfusion remained intact. Thus, no surgical intervention was undertaken. However, anticoagulation and prostaglandin therapy was initiated and the flap was salvaged. Genetic analysis uncovered a polymorphism in the prothrombin genes. The flap remained viable and without further complications until the last follow‐up visit at 36 weeks after microsurgical reconstruction. The patient was fully mobilized with complete return to function. Near‐infrared guided fluorescence imaging may be a viable tool for the assessment of late fasciocutaneous free flap complications and guide the decision‐making process.
On the Misleading Use of for QSAR Model Comparison
Authors: Consonni Viviana , Todeschini Roberto , Ballabio Davide , Grisoni Francesca
Published: August 2018

Quantitative Structure – Activity Relationship (QSAR) models play a central role in medicinal chemistry, toxicology and computer‐assisted molecular design, as well as a support for regulatory decisions and animal testing reduction. Thus, assessing their predictive ability becomes an essential step for any prospective application. Many metrics have been proposed to estimate the model predictive ability of QSARs, which have created confusion on how models should be evaluated and properly compared. Recently, we showed that the metric
is particularly well‐suited for comparing the external predictivity of different models developed on the same training dataset. However, when comparing models developed on different training data, this function becomes inadequate and only dispersion measures like the root‐mean‐square error (RMSE) should be used. The intent of this work is to provide clarity on the correct and incorrect uses of
, discussing its behavior towards the training data distribution and illustrating some cases in which
estimates may be misleading. Hereby, we encourage the usage of measures of dispersions when models trained on different datasets have to be compared and evaluated.
Autosegmentation for thoracic radiation treatment planning: A grand challenge at AAPM 2017
Authors: Yang Jinzhong , Veeraraghavan Harini , Armato Samuel G. , Farahani Keyvan , Kirby Justin S. , Kalpathy‐Kramer Jayashree , van Elmpt Wouter , Dekker Andre , Han Xiao , Feng Xue , Aljabar Paul , Oliveira Bruno , van der Heyden Brent , Zamdborg Leonid , Lam Dao , Gooding Mark , Sharp Gregory C.
Published: August 2018

Purpose

This report presents the methods and results of the Thoracic Auto‐Segmentation Challenge organized at the 2017 Annual Meeting of American Association of Physicists in Medicine. The purpose of the challenge was to provide a benchmark dataset and platform for evaluating performance of autosegmentation methods of organs at risk (OARs) in thoracic CT images.

Methods

Sixty thoracic CT scans provided by three different institutions were separated into 36 training, 12 offline testing, and 12 online testing scans. Eleven participants completed the offline challenge, and seven completed the online challenge. The OARs were left and right lungs, heart, esophagus, and spinal cord. Clinical contours used for treatment planning were quality checked and edited to adhere to the RTOG 1106 contouring guidelines. Algorithms were evaluated using the Dice coefficient, Hausdorff distance, and mean surface distance. A consolidated score was computed by normalizing the metrics against interrater variability and averaging over all patients and structures.

Results

The interrater study revealed highest variability in Dice for the esophagus and spinal cord, and in surface distances for lungs and heart. Five out of seven algorithms that participated in the online challenge employed deep‐learning methods. Although the top three participants using deep learning produced the best segmentation for all structures, there was no significant difference in the performance among them. The fourth place participant used a multi‐atlas‐based approach. The highest Dice scores were produced for lungs, with averages ranging from 0.95 to 0.98, while the lowest Dice scores were produced for esophagus, with a range of 0.55–0.72.

Conclusion

The results of the challenge showed that the lungs and heart can be segmented fairly accurately by various algorithms, while deep‐learning methods performed better on the esophagus. Our dataset together with the manual contours for all training cases continues to be available publicly as an ongoing benchmarking resource.
Early diabetic retinopathy diagnosis based on local retinal blood vessel analysis in optical coherence tomography angiography (OCTA) images
Authors: Eladawi Nabila , Elmogy Mohammed , Khalifa Fahmi , Ghazal Mohammed , Ghazi Nicola , Aboelfetouh Ahmed , Riad Alaa , Sandhu Harpal , Schaal Shlomit , El‐Baz Ayman
Published: August 2018

Purpose

This paper introduces a new computer‐aided diagnosis (CAD) system for detecting early‐stage diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) images.

Methods

The proposed DR‐CAD system is based on the analysis of new local features that describe both the appearance and retinal structure in OCTA images. It starts with a new segmentation approach that has the ability to extract the blood vessels from superficial and deep retinal OCTA maps. The high capability of our segmentation approach stems from using a joint Markov–Gibbs random field stochastic model integrating a 3D spatial statistical model with a first‐order appearance model of the blood vessels. Following the segmentation step, three new local features are estimated from the segmented vessels and the foveal avascular zone (FAZ): (a) vessels density, (b) blood vessel calibre, and (c) width of the FAZ. To distinguish mild DR patients from normal cases, the estimated three features are used to train and test a support vector machine (SVM) classifier with the radial basis function (RBF) kernel.

Results

On a cohort of 105 subjects, the presented DR‐CAD system demonstrated an overall accuracy (ACC) of 94.3%, a sensitivity of 97.9%, a specificity of 87.0%, the area under the curve (AUC) of 92.4%, and a Dice similarity coefficient (DSC) of 95.8%. This in turn demonstrates the promise of the proposed CAD system as a supplemental tool for early detection of DR.

Conclusion

We developed a new DR‐CAD system that is capable of diagnosing DR in its early stage. The proposed system is based on extracting three different features from the segmented OCTA images, which reflect the changes in the retinal vasculature network.
I give at the office: A review of workplace giving research, theory, and practice
Authors: Shaker Genevieve G. , Christensen Robert K.
Published: August 2018

Workplace giving is a widely used philanthropic tool. Although it may have great unmet potential, it is also facing a number of challenges, including competition from informal crowdfunding campaigns. In the face of such challenges, we take stock of the extant research to better understand the value and future of workplace giving, emphasizing employee actions and preferences in our review. Workplace giving studies can also augment knowledge about contextual giving or bounded settings for exploring basic philanthropic questions (e.g., donor control or gift elasticity). We use a three‐part conceptual framework to synthesize and discuss research on individual workplace giving in the context of broader giving behaviors. We address what researchers know, do not know, and need to know on the topic of workplace giving.
Growing disparities in an urban food desert: Downtown Albany longitudinal food environment studies
Authors: Hosler Akiko S.
Published: August 2018

This paper presents findings from our longitudinal study of food environments in two exemplary, contrasting urban neighborhoods in Downtown Albany, New York. The “minority neighborhood” (74% racial/ethnic minority population) is a “food desert” by the United States Department of Agriculture's definition, whereas the adjacent “mixed neighborhood” (33% minority population) is not. The long‐term trend analysis (1970–2018) of the macro‐level food environment found that although the minority neighborhood lost all supermarkets and remains supermarket‐less since the late 1990s, the mixed neighborhood was able to retain several supermarkets and since 2008, it gained a new supermarket every 3–5 years. The medium‐term trend analysis (2003–2015) of the micro‐level food environment revealed a more complex picture of changing food environments. The total number of food stores in the minority neighborhood increased in much greater rates than the mixed neighborhood in the 12‐year period, and accordingly, the standardized availability measures for “any” fresh fruits and fresh vegetables increased significantly in the minority neighborhood. The standardized availability measure for adequate (five or more) varieties of nutritionally desirable fresh fruits and vegetables, however, did not increase in the minority neighborhood. Because the mixed neighborhood saw steady increases in such measures, disparities between the two neighborhoods grew incrementally and reached the highest point (rate ratio of over 5.0) in 2015. In this paper, there are also sections to provide historical and contextual background of our food environment research, as well as discussion on intervention ideas to address the disparities in fresh produce availability focusing on ethnic markets.
An Overview of Hyperinsulinemic‐Euglycemic Therapy in Calcium Channel Blocker and β‐blocker Overdose
Authors: Krenz James R. , Kaakeh Yaman
Published: August 2018

Both calcium channel blockers (CCBs) and β blockers (BBs) are associated with fatal substance exposures within the United States. Cases of overdose with these agents have the potential to be both complex and difficult to manage. A variety of pharmacologic treatment options are available for clinicians to use to help mitigate harm from these poisonings. Hyperinsulinemic‐euglycemic therapy (HIET) was once regarded as a last‐ditch effort to treat patients in highly refractory cases. In recent years, this therapy has become a routine therapy in the treatment of CCB/BB overdose. This article provides a literature review regarding HIET in cases of overdose with CCB and BB agents. Relevant literature articles from 1997–2018 were identified and reviewed using the PubMed and Embase databases. The following search terms were used to identify potential articles: “hyperinsulinemic‐euglycemic therapy,” “overdose,” “calcium channel blocker,” “beta blocker,” and “insulin.” Articles published in the English language were included in this review. A manual search of reference lists was also conducted. Much of the literature is limited to case reports, series, retrospective chart reviews, and small prospective studies. The success rate observed in published case series ranged from 80.4–100%. Regular insulin is most commonly dosed at an initial bolus of 1 unit/kg followed by a regular insulin infusion of 0.5–1 unit/kg/hour. Euglycemia is often maintained using intravenous fluids containing dextrose. Hyperinsulinemic‐euglycemic therapy exhibited a promising safety profile, provided close monitoring is conducted. More research is needed to determine optimal strategies for maintaining euglycemia, ideal monitoring parameters, and consistent efficacy goals.