bluuebunny/crossref_metadata_2025 huggingface dataset:
External quality assurance in nongynecologic cytology: The Australasian experience
Authors: Shield Paul W. , Frost Felicity , Finnimore Jo L. , Wright R. Gordon , Cummings Margaret C.
Published: February 2017

BACKGROUND

The Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program has operated an external quality assurance program in nongynecologic cytopathology since 1993. Glass slide preparations of a wide range of nongynecologic cases were circulated to approximately 200 cytopathology laboratories in 16 countries.

METHODS

General nongynecologic cytology cases were manufactured from residual specimens after routine diagnosis. Fine‐needle aspiration (FNA) cases were made by sampling fresh tissue and making direct specimens. The majority of cases consisted of both air‐dried and fixed preparations. Results returned to laboratories included illustrated case discussions highlighting diagnostic features, key differential diagnoses, and useful adjunctive tests.

RESULTS

The current study reviewed >22,000 results for 123 nongynecologic cases. Cases found to cause the most diagnostic difficulties included serous effusion cases with metastatic carcinoma in a dispersed pattern, well‐differentiated carcinoma, and cellular reactive cases; urine specimens with sparse malignant cells; reactive pneumocytes in a bronchoalveolar lavage; breast FNA cases with papillary lesions; gestational specimens; and fibroadenoma. FNA specimens from the lung and thyroid, particularly papillary thyroid carcinoma, generally were well reported.

CONCLUSIONS

The use of multiple preparations of the same specimen has allowed interlaboratory comparison, and the quality assurance program has played an educational role as well as informing the laboratory accreditation process. Cancer Cytopathol 2017;125:349–361. © 2017 American Cancer Society.
Synthesis of flower‐like Bi2S3/Cu7.2S4 composites and their photocatalytic performance
Authors: Chen Shenghua , Yin Hanquan , Zeng Dongming , Chen Limiao
Published: February 2017

Hybrid materials exhibit unique optical and catalytic properties that are dependent on their composition, morphology and structure. In this work, Bi2S3/Cu7.2S4 composites with flower‐like morphology have been successfully prepared via a facile and effective approach based on a hydrothermal method and an ion‐exchange reaction. The molar composition of Bi and Cu in the Bi2S3/Cu7.2S4 composites can be simply modulated by changing the amount of CuCl2·2H2O. The photocatalytic activity of the obtained product was evaluated through the photodegradation of Rhodamine B (RhB) under visible light irradiation. The results show clearly that the Bi2S3/Cu7.2S4 composites possess a much high photocatalytic activity (about 92.2 % of RhB was degraded within 75 min) than pure Bi2S3 and copper sulfide particles. This work provides useful insight into the rational design and preparation of novel and effective chalcogenide‐based hybrid photocatalysts.
Analysis of drugs of abuse in Cerumen ‐ correlation of postmortem analysis results with those for blood, urine and hair
Authors: Meier Sylvia I. , Koelzer Sarah C. , Schubert‐Zsilavecz Manfred , Toennes Stefan W.
Published: February 2017

The evaluation of drug and alcohol abuse is a major subject of forensic toxicology. Assessment of drug abstinence currently requires the analysis of urine or hair. In the present study cerumen, a mixture of sebum and sweat, was tested as an alternative.

Postmortem samples (blood, urine, hair and cerumen from 38 corpses) were analyzed using liquid chromatography and gas chromatography, each coupled to mass spectrometry (LC–MS, GC–MS). The results were compared.

In all cases of recent drug use (i.e. detection of opiates, amphetamine and derivatives, cocaine, methadone and diazepam or their metabolites in blood) the corresponding cerumen was positive. In 3 cases, where drugs could only be detected in urine, cerumen was also found to be positive. Even in cases where only hair was positive cerumen still contained analytes in some instances (52.5%). However, cannabis use was only detected in 31.6% of cerumen samples of the deceased cannabis users. Unexpectedly, not tetrahydrocannabinol (THC) was detected but its oxidized form, cannabinol.

The present results suggest that cerumen is a promising alternative for drugs of abuse testing. The detection time window of cerumen is obviously in excess of that of urine but not as long as with hair. However, current problems with the detection of cannabinoids require further research. Copyright © 2017 John Wiley & Sons, Ltd.
The theory of island biogeography applies to ectomycorrhizal fungi in subalpine tree “islands” at a fine scale
Authors: Glassman Sydney I. , Lubetkin Kaitlin C. , Chung Judy A. , Bruns Thomas D.
Published: February 2017

The theory of island biogeography, which predicts that species richness is a function of island size and distance from the mainland, is well tested with macro‐fauna and flora. Yet, in many ways, microbes are more appropriate for testing this and other ecological theories due to their small size and short generation times that translate to an ease of replication. We used a natural experimental system of isolated “host islands” to test the generality of the theory of island biogeography. Specifically, we tested whether ectomycorrhizal fungal (EMF) richness increased with tree size and decreased with distance from forest in a subalpine basin in Yosemite National Park for two congeneric pine species, Pinus albicaulis and Pinus contorta. We determined EMF richness with next‐generation sequencing, measured the size and age of each tree island (n = 40), and calculated geographic distances from each tree to the nearest forest edge. We found that EMF richness increased with island size (as measured by tree volume) and tree age for both pine species and decreased with distance from forest edge for P. albicaulis. Thus, we show the applicability of the theory to microbial symbionts in harsh, dry, and likely non‐equilibrium systems. In addition, we found that despite the fact that our tree islands had a mean age of 65 yr, a pioneer community of EMF dominated. We interpret this as evidence that water stress interacts with succession to create a sustained period of early‐stage fungi even in mature trees.
Passerine morphology: external measurements of approximately one‐quarter of passerine bird species
Authors: Ricklefs Robert E.
Published: February 2017

Studies of community organization and clade diversification that include functional traits have become an important component of the analysis of ecological and evolved systems. Such studies frequently are limited by availability of consistently collected data. Here, I present a data set including eight measurements of the external morphology of 1642 species, roughly one‐quarter of all passerine birds (Aves: Order Passeriformes), from all parts of the world, characterizing the relative proportions of the wing, tail, legs, and beak. Specimens were measured opportunistically over the past 40 years in museums in the United States and Europe. Numbers of individuals measured per species vary from one to dozens in some cases. Measurements for males and females of sexually size‐dimorphic species are presented separately. The measurements include total length, the lengths of the wing, tail, tarsus, and middle toe, and the length, breadth, and depth of the beak. Particular attention was paid to obtaining a broad representation of passerine higher taxa, with special interest in small families and subfamilies of passerines, as well as species produced by evolutionary radiations of birds in archipelagoes, including the Galapagos, Hawaii, and the Lesser Antilles. Taxonomy follows the Taxonomy in Flux (TIF) checklist as well as the World Bird List of the International Ornithological Council. Geographic distributions are summarized from Edwards's Coded List of Birds of the World. Coverage of taxa and geographic regions varies and reflects the changing interests of the author over the past four decades. North American and South American species are particularly well represented in the sample, as well as species belonging to the families Tyrannidae, Furnariidae, Thamnophilidae, Mimidae, Sturnidae, Fringillidae, Parulidae, Icteridae, Cardinalidae, and Thraupidae.
An experimental test of fitness variation across a hydrologic gradient predicts willow and poplar species distributions
Authors: Wei Xiaojing , Savage Jessica A. , Riggs Charlotte E. , Cavender‐Bares Jeannine
Published: February 2017

Environmental filtering is an important community assembly process influencing species distributions. Contrasting species abundance patterns along environmental gradients are commonly used to provide evidence for environmental filtering. However, the same abundance patterns may result from alternative or concurrent assembly processes. Experimental tests are an important means to decipher whether species fitness varies with environment, in the absence of dispersal constraints and biotic interactions, and to draw conclusions about the importance of environmental filtering in community assembly. We performed an experimental test of environmental filtering in 14 closely related willow and poplar species (family Salicaceae) by transplanting cuttings of each species into 40 common gardens established along a natural hydrologic gradient in the field, where competition was minimized and herbivory was controlled. We analyzed species fitness responses to the hydrologic environment based on cumulative growth and survival over two years using aster fitness models. We also examined variation in nine drought and flooding tolerance traits expected to contribute to performance based on a priori understanding of plant function in relation to water availability and stress. We found substantial evidence that environmental filtering along the hydrologic gradient played a critical role in determining species distributions. Fitness variation of each species in the field experiment was used to model their water table depth optima. These optima predicted 68% of the variation in species realized hydrologic niches based on peak abundance in naturally assembled communities in the surrounding region. Multiple traits associated with water transport efficiency and water stress tolerance were correlated with species hydrologic niches, but they did not necessarily covary with each other. As a consequence, species occupying similar hydrologic niches had different combinations of trait values. Moreover, individual traits were less phylogenetically conserved than species hydrologic niches and integrated water stress tolerance as determined by multiple traits. We conclude that differential fitness among species along the hydrologic gradient was the consequence of multiple traits associated with water transport and water stress tolerance, expressed in different combinations by different species. Varying environmental tolerance, in turn, played a critical role in driving niche segregation among close relatives along the hydrologic gradient.
ESIPT‐Induced Carbazole‐Based AIEE Material for Nanomolar Detection of Cu2+ and CN– Ions: A Molecular Keypad Security Device
Authors: Sharma Shilpa , Virk Tarunpreet Singh , Pradeep Chullikkattil P. , Dhir Abhimanew
Published: February 2017

Herein, we have designed and synthesized a new diimino dicarbazole derivative, 3, which exhibits the phenomenon of aggregation‐induced emission enhancement (AIEE) due to the persistence of the excited‐state intramolecular proton transfer phenomenon. The aggregates of AIEE‐active material 3 selectively sense Cu2+ ions in the nanomolar range and mediate the conversion of Cu2+ ions to Cu nanorods. The ensemble of aggregates of 3 and Cu nanorods were further utilized for selective sensing of CN– ions. In addition, the fluorescence behavior of the system generates the formation of a molecular keypad security device. The keypad security device, based on AIEE material, adds to the complexity of the lock and makes it more efficient.
Restriction of oil migration in tahini halva via organogelation
Authors: Öğütcü Mustafa , Arifoğlu Nazan , Yılmaz Emin
Published: February 2017

Tahini halva is a famous traditional confectionery product mostly consumed in the Middle East, Mediterranean, and Balkan countries, with a continuously rising consumption rates. With the increase in production, problems such as oil migration, causing an unpleasant appearance are emerging especially during prolonged storage of halva products. Thus, in the present study, tahini halva was prepared via organogelation technique with natural organogelators such as sunflower, shellac, and beeswax at different addition levels (1, 3, and 5%) and the effect of these additives on preventing the oil migration was evaluated by comparing with a commercial emulsifier (hydrogenated palm stearine). The evaluation of the physico–chemical, morphological, textural, and sensory properties of the halva samples revealed that sunflower and shellac wax at 3 and 5% addition levels led to a reasonable reduction of the oil migration problem and these products were quite similar with the control sample containing hydrogenated palm stearine. Furthermore, in all samples oil leakage was below 7%. Addition of the natural waxes did not negatively affect the textural and sensory properties of tahini halva. In conclusion, shellac and sunflower wax might be successfully used instead of hydrogenated palm stearine in confectioneries such as tahini halva.

Practical applications: Oil migration is one of the major problem in oil based food products such as chocolate, emulsions, fillings, confectionery, and halva. This problem can cause quality and nutritional problems, as well as economical losses in food industry. In this reason, natural waxes were used to prevent oil migration in tahini halva. Tahini halva can be successfully prepared with natural waxes and the textural properties of tahini halva are not negatively affected by addition of natural waxes. Organogelation is effective in restricting oil migration in tahini halva. Natural waxes, sunflower, shellac, and beeswax, may reduce use of hydrogenated food additives as oil stabilizers in halva processing.

Natural waxes are at least as effective as hydrogenated palm stearine for improving the oil separation problem in tahini halva.
Total Synthesis and in Vivo Quantitation of Phytofurans Derived from α‐Linolenic Acid
Authors: Cuyamendous Claire , Leung Kin Sum , Bultel‐Poncé Valérie , Guy Alexandre , Durand Thierry , Galano Jean‐Marie , Lee Jetty Chung‐Yung , Oger Camille
Published: February 2017

Phytoprostanes (PhytoPs) are produced in plants and seeds by non‐enzymatic free‐radical pathways from α‐linolenic acid (ALA). We recently highlighted the formation of a new class of compounds from ALA, namely phytofurans (PhytoFs). In biological samples, these compounds are produced as mixtures, and their analytical exploration remains challenging without their pure synthetic forms. The synthesis of some phytofurans is described here. The use of an enantiomerically enriched intermediate allowed for the first time access to both families of PhytoFs, the alkenyl and enediol classes. For the first time, PhytoF metabolites have been quantitated in the liver tissue of rats treated with an ALA‐rich flaxseed or flaxseed oil diet.
Cyclic Lipopeptide Antibiotic Daptomycin Electrochemical Oxidation at a Glassy Carbon Electrode
Authors: Machini Wesley B. S. , Oliveira‐Brett A. M.
Published: February 2017

Daptomycin was the first approved drug from a new class of antimicrobials, the cyclic lipopeptides, and presents a broad spectrum of activity against a wide range of gram‐positive bacteria. The daptomycin redox behaviour, by cyclic, differential pulse and square wave voltammetry, in a wide pH range, at a glassy carbon electrode, was investigated. The daptomycin oxidation was a two‐step irreversible diffusion‐controlled process and the diffusion coefficient DDPT = 2.32 × 10−5 cm2 s−1, was calculated. A detection limit LOD = 0.32 μM, was obtained. For the first time daptomycin, in fetal bovine serum biological fluid, using DP voltammetry, was determined.
Electrochemical Simultaneous Sensing of Melatonin, Dopamine and Acetaminophen at Platinum Doped and Decorated Alpha Iron Oxide
Authors: Manikandan Palinci Nagarajan , Dharuman Venkataraman
Published: February 2017

Simultaneous sensing of dopamine (DA), acetaminophen (AP) and melatonin (MEL) was made by electrochemical method as the drugs melatonin and acetaminophen interact with dopamine in brain to induce neuro disorders. The glassy carbon electrode surface was modified with un‐doped α‐ Fe2O3, platinum doped Fe2O3 (dPtFe2O3), Pt decorated Fe2O3 (sPtFe2O3) and doped and decorated Fe2O3 (sdPtFe2O3) nano particles that are synthesized by co‐precipitation method in presence of polyethylene glycol for the first time. These particles were characterized using Ultra‐Violet Visible (UV‐Vis), scanning electron microscopy (SEM), X‐ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA) and electrochemical techniques. The sdPtFe2O3 showed the highest catalytic activity than the dPtFe2O3, sPtFe2O3 and un‐doped α‐ Fe2O3 with well separated voltammetric peaks for DA and AP in presence of MEL. This is attributed to higher surface hydration effects of the sdPtFe2O3, dPtFe2O3 and sPtFe2O3 than the un‐doped Fe2O3 which plays a vital role in enhancing the melatonin sensing in presence of dopamine and acetaminophen. Linear ranges and lowest detection limits for all three analytes were increased by 10 times for the sdPtFe2O3 compared to other Fe2O3 modified electrodes. The sensor is validated using commercially available pharmaceutical drugs used in therapeutics.
Further Ahead with Electrochemical Energy Technology
Authors: Stimming Ulrich , Bele Petra
Published: February 2017

No abstract.
Complementary medicine for treatment of agitation and delirium in older persons: a systematic review and narrative synthesis
Authors: Levy Ilana , Attias Samuel , Ben‐Arye Eran , Bloch Boaz , Schiff Elad
Published: February 2017

Background

Agitation and delirium frequently occur in cognitively impaired older people. We conducted a systematic review with narrative synthesis of the literature aiming to assess effectiveness of complementary and alternative medicine (CAM) modalities to address these conditions.

Methods

Following preliminary search, we included 40 original researches on CAM treatment of delirium and agitation in older persons. Then, the quality of these studies was assessed using the Downs and Black Checklist and Quality Assessment Tool for Studies with Diverse Designs, and the effect sizes were calculated. We subsequently conducted a narrative synthesis of the main findings, including theory development, preliminary synthesis, exploration of relationships within and between studies, and assessment of synthesis robustness.

Results

Forty articles that met the inclusion criteria were analyzed. Sixteen of these were randomized controlled trials. One article specifically addressed CAM treatment of delirium in patients without dementia, and the remaining 39 articles described treatments of agitated older persons with dementia. Thirty‐five of the 40 included studies suggested that the investigated CAM therapies may ameliorate the severity of agitation and delirium. The physiological surrogates of agitation assessed in these studies included cortisol level, chromogranin A level, and heart rate variability. Very few of the studies systematically assessed safety issues, although no major adverse effects were reported.

Conclusion

Overall, the systematic review of the literature suggests that several CAM modalities are potentially beneficial in the treatment of agitation and delirium among older persons. We suggest that promising CAM modalities should be further explored through large‐scale randomized controlled trials in different clinical settings. Copyright © 2017 John Wiley & Sons, Ltd.
Neuropsychiatric symptoms in South‐East Asian patients with mild cognitive impairment and dementia: prevalence, subtypes, and risk factors
Authors: Yatawara Chathuri , Hiu Shaun , Tan Laura , Kandiah Nagaendran
Published: February 2017

Background

The subtypes and risk factors of neuropsychiatric symptoms remain largely unexplored in South‐East Asian populations.

Objective

We investigated the prevalence, subtypes, and risk factors, namely, demographic, medical morbidity, and cognitive impairment associated with neuropsychiatric symptoms in a South‐East Asian cohort of patients with mild cognitive impairment (MCI) and dementia.

Methods

A clinical cohort of 38 MCI and 198 mild–moderate dementia patients were assessed using the Neuropsychiatric Inventory‐Questionnaire.

Results

Neuropsychiatric symptoms were equally prevalent among patients with MCI (74%) and mild–moderate dementia (85%). Three subtypes of symptoms were identified for each diagnostic group; for MCI, they included mood disturbances, anxiety/sleep problems, and psychosis, while for dementia, the subtypes included behavioral disturbances, psychosis/mood, and hyperactive behaviors. The largest risk for neuropsychiatric symptoms for both MCI and dementia patients was male gender. Among patients with MCI, burden of cerebrovascular disease and global cognitive impairment were small risks for neuropsychiatric symptoms, while for patients with dementia, an older age (>65 years) was a small risk and lower educational attainment was a moderate risk.

Discussion

These findings contribute to the worldwide epidemiology of neuropsychiatric symptoms in MCI and dementia and highlight that the profile of symptoms, subtypes, and risks is fairly homogenous across Western and Asian cultures. Copyright © 2017 John Wiley & Sons, Ltd.
The impact of anxiety on the progression of mild cognitive impairment to dementia in Chinese and English data bases: a systematic review and meta‐analysis
Authors: Li Xiao‐Xue , Li Zheng
Published: February 2017

Objective

It remains unclear whether or not anxiety increases the risk of dementia in people with mild cognitive impairment (MCI). The aim of this systematic review and meta‐analysis was to investigate the risk of dementia among people with MCI and anxiety compared with those with MCI and no anxiety.

Methods

The hazard ratio of conversion to dementia in people with anxiety and MCI was compared with those without anxiety and was calculated using a generic inverse variance method with fixed effect models.

Results

Eleven studies from the English and Chinese databases were included, seven of which were included in the meta‐analysis. The pooled hazard ratio of conversion to dementia was 1.18 95% CI [1.07, 1.31] (p = 0.002) in the group of MCI plus anxiety compared with those without anxiety.

Conclusion

The results suggest that anxiety increases the risk of progression to dementia in people with MCI. Future interventions targeting anxiety management in vulnerable people with MCI may reduce the risk of dementia. Copyright © 2017 John Wiley & Sons, Ltd.
Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease
Authors: Fernández‐Matarrubia Marta , Matías‐Guiu Jordi A. , Cabrera‐Martín María Nieves , Moreno‐Ramos Teresa , Valles‐Salgado María , Carreras José Luis , Matías‐Guiu Jorge
Published: February 2017

Objectives

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18F fluorodeoxyglucose (FDG‐PET).

Methods

Forty‐two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG‐PET brain scan to provide data for voxel‐based morphometric analysis.

Results

Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self‐awareness in comparison with AD sample. Additionally, FDG‐PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD.

Conclusions

These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG‐PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd.
Coronary artery calcification and cognitive function: cross‐sectional results from the ELSA‐Brasil study
Authors: Suemoto Claudia K. , Bittencourt Marcio S. , Santos Itamar S. , Benseñor Isabela M. , Lotufo Paulo A.
Published: February 2017

Objectives

We examined the relationship between coronary artery calcification (CAC) score and performance in cognitive tests in a large Brazilian sample.

Methods

In this cross‐sectional study, 4104 participants (mean age = 50.9 ± 8.8 years old, 54% female) from the Brazilian Longitudinal Study of Adult Health had complete information for CAC and cognitive tests. We used linear regression models adjusted for sociodemographics, cardiovascular risk factors (hypertension, diabetes, smoking, alcohol use, physical activity, and body mass index), depression, and thyroid function. To investigate potential different associations for middle‐aged and older adults, we stratified the analysis by age groups.

Results

Participants with CAC ≥ 100 Agatston score had poorer performance in the trail making test compared to those with CAC < 100 Agatston score (β = −0.101, 95% CI = −0.194; −0.010, p = 0.03). We did not find any other association between CAC and cognitive tests. When we investigated the effect modification between CAC and age on cognitive tests, only the effect modification on global cognition (p = 0.02) and trail making test was significant (p = 0.0003).

Conclusions

Higher CAC was weakly associated with poorer performance in an executive function test in a large sample from the Brazilian Longitudinal Study of Adult Health. Copyright © 2017 John Wiley & Sons, Ltd.
Abnormal task driven neural oscillations in multiple sclerosis: A visuomotor MEG study
Authors: Barratt Eleanor L. , Tewarie Prejaas K. , Clarke Margareta A. , Hall Emma L. , Gowland Penny A. , Morris Peter G. , Francis Susan T. , Evangelou Nikos , Brookes Matthew J.
Published: February 2017

Multiple sclerosis (MS) is a debilitating disease commonly attributed to degradation of white matter myelin. Symptoms include fatigue, as well as problems associated with vision and movement. Although areas of demyelination in white matter are observed routinely in patients undergoing MRI scans, such measures are often a poor predictor of disease severity. For this reason, it is instructive to measure associated changes in brain function. Widespread white‐matter demyelination may lead to delays of propagation of neuronal activity, and with its excellent temporal resolution, magnetoencephalography can be used to probe such delays in controlled conditions (e.g., during a task). In healthy subjects, responses to visuomotor tasks are well documented: in motor cortex, movement elicits a localised decrease in the power of beta band oscillations (event‐related beta desynchronisation) followed by an increase above baseline on movement cessation (post‐movement beta rebound (PMBR)). In visual cortex, visual stimulation generates increased gamma oscillations. In this study, we use a visuomotor paradigm to measure these responses in MS patients and compare them to age‐ and gender‐matched healthy controls. We show a significant increase in the time‐to‐peak of the PMBR in patients which correlates significantly with the symbol digit modalities test: a measure of information processing speed. A significant decrease in the amplitude of visual gamma oscillations in patients is also seen. These findings highlight the potential value of electrophysiological imaging in generating a new understanding of visual disturbances and abnormal motor control in MS patients. Hum Brain Mapp 38:2441–2453, 2017. © 2017 Wiley Periodicals, Inc.
ROBO1 polymorphisms, callosal connectivity, and reading skills
Authors: Sun Xiaochen , Song Shuang , Liang Xinyu , Xie Yachao , Zhao Chenxi , Zhang Yuping , Shu Hua , Gong Gaolang
Published: February 2017

The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon‐guidance‐receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading‐related ROBO1 polymorphisms were genotyped, and diffusion and structural MRI were acquired to measure the fiber microstructure of the corpus callosum (CC), the major white‐matter tract that connects inter‐hemispheric cortical regions. The results confirmed the significant influence of the ROBO1 polymorphisms on reading scores. The fiber microstructures of the midline‐CC segments around the genu and splenium were also affected by the ROBO1 polymorphisms. Moreover, a mediation analysis further revealed that the genu could significantly mediate the effects of the ROBO1 polymorphisms on word‐list reading performance, which suggests a ROBO1‐to‐genu‐to‐reading pathway. The genu‐linked cortical morphology, however, was not associated with either the ROBO1 polymorphisms or reading performance. These findings offer direct evidence supporting ROBO1‐callosum association in humans and also provide valuable insight into the functions of ROBO1 and the gene‐to‐brain mechanisms that underlie human reading. Hum Brain Mapp 38:2616–2626, 2017. © 2017 Wiley Periodicals, Inc.
microRNA‐200a: A stage‐dependent biomarker and predictor of steatosis and liver cell injury in human immunodeficiency virus patients
Authors: Austermann Christian , Schierwagen Robert , Mohr Raphael , Anadol Evrim , Klein Sabine , Pohlmann Alessandra , Jansen Christian , Strassburg Christian P. , Schwarze‐Zander Carolynne , Boesecke Christoph , Rockstroh Jürgen K. , Odenthal Margarete , Trebicka Jonel
Published: February 2017

Nonalcoholic fatty liver disease contributes to liver‐related mortality and has a high prevalence among patients with human immunodeficiency virus (HIV). The early detection of steatosis could prevent disease progression through life‐style changes. However, as the common serum markers are nonspecific and the gold standard for the detection of nonalcoholic fatty liver disease remains the invasive liver biopsy, its verification is limited. Therefore, the search for novel biomarkers is essential. Several studies have emphasized the role of microRNAs (miRNAs) as biomarkers for certain liver diseases. With our study, we aimed to investigate the potential of miR‐200a as a biomarker for liver injury, fibrosis, and steatosis in HIV patients. The study cohort consisted of 89 HIV patients. Clinical and laboratory parameters were assessed twice, within a median follow‐up period of 12 months. miR‐200a serum levels were determined by real‐time polymerase chain reaction and normalized to spiked‐in RNA (SV40). miR‐200a serum levels showed a significant correlation with the patients' controlled attenuation parameter scores and their body weight at baseline and with alanine aminotransferase serum levels at follow‐up. At baseline, we observed a stage‐dependent increase in miR‐200a serum levels according to the degree of steatosis. More importantly, patients with higher baseline levels of miR‐200a recorded a progression of steatosis at follow‐up. Remarkably, miR‐200a not only reveals a prognostic value for steatosis but possibly also for liver damage and metabolic adaptions as patients with an increase in alanine aminotransferase/aspartate aminotransferase serum levels over time also recorded higher baseline miR‐200a levels.
Conclusion
: Our study reveals miR‐200a not only to be a stage‐dependent biomarker of steatosis but also to be a predictor of steatosis progression and probably liver cell injury in HIV patients. (Hepatology Communications 2017;1:36–45)
Effects of a sodium‐glucose cotransporter 2 inhibitor in nonalcoholic fatty liver disease complicated by diabetes mellitus: Preliminary prospective study based on serial liver biopsies
Authors: Akuta Norio , Watanabe Chizuru , Kawamura Yusuke , Arase Yasuji , Saitoh Satoshi , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Suzuki Yoshiyuki , Suzuki Fumitaka , Ikeda Kenji , Kumada Hiromitsu
Published: February 2017

A prospective study based on serial liver biopsies was performed to investigate the efficacy of sodium‐glucose cotransporter 2 inhibitor for nonalcoholic fatty liver disease complicated with type 2 diabetes mellitus. Conclusion: Treatment for 24 weeks resulted in improvement in histopathologic features in all 5 patients. (Hepatology Communications 2017;1:46–52)
The role of exosomes and miRNAs in drug‐resistance of cancer cells
Authors: Bach Duc‐Hiep , Hong Ji‐Young , Park Hyen Joo , Lee Sang Kook
Published: February 2017

Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40–150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell‐to‐cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer‐secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome‐wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV‐mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment.
Early detection of pancreatic cancer: Where are we now and where are we going?
Authors: Zhou Bin , Xu Jian‐Wei , Cheng Yu‐Gang , Gao Jing‐Yue , Hu San‐Yuan , Wang Lei , Zhan Han‐Xiang
Published: February 2017

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various “omics” studies including genomics, epigenomics, non‐coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.
Preparation and characterization of 45S5 bioactive glass‐based scaffolds loaded with PHBV microspheres with daidzein release function
Authors: Macías‐Andrés Víctor I. , Li Wei , Aguilar‐Reyes Ena A. , Ding Yaping , Roether Judith A. , Harhaus Leila , León‐Patiño Carlos A. , Boccaccini Aldo R.
Published: February 2017

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) microsphere loaded 45S5 bioactive glass (BG) based scaffolds with drug releasing capability have been developed. PHBV microspheres with a mean particle size 4 ± 2 μm loaded with daidzein were obtained by oil‐in‐water single emulsion solvent evaporation method and applied to the surface of BG scaffolds by dip coating technique. The morphology, in vitro bioactivity in simulated body fluid (SBF), mechanical properties and drug release kinetics of microsphere loaded scaffolds were studied. The microspheres were shown to be homogeneously dispersed on the scaffold surfaces. It was confirmed that hydroxyapatite crystals homogeneously grew not only on the surface of the scaffold but also on the surface of the microspheres within 3 days of immersion in SBF. The daidzein release from the microsphere loaded scaffolds lasted almost 1 month and was determined to be diffusion controlled. The microsphere loaded BG scaffolds with daidzein releasing capability obtained in this study are a candidate for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1765–1774, 2017.
An engineered macroencapsulation membrane releasing FTY720 to precondition pancreatic islet transplantation
Authors: Bowers Daniel T. , Olingy Claire E. , Chhabra Preeti , Langman Linda , Merrill Parker H. , Linhart Ritu S. , Tanes Michael L. , Lin Dan , Brayman Kenneth L. , Botchwey Edward A.
Published: February 2017

Macroencapsulation is a powerful approach to increase the efficiency of extrahepatic pancreatic islet transplant. FTY720, a small molecule that activates signaling through sphingosine‐1‐phosphate receptors, is immunomodulatory and pro‐angiogenic upon sustained delivery from biomaterials. While FTY720 (fingolimod, Gilenya) has been explored for organ transplantation, in the present work the effect of locally released FTY720 from novel nanofiber‐based macroencapsulation membranes is explored for islet transplantation. We screened islet viability during culture with FTY720 and various biodegradable polymers. Islet viability is significantly reduced by the addition of high doses (≥500 ng/mL) of soluble FTY720. Among the polymers screened, islets have the highest viability when cultured with poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV). Therefore, PHBV was blended with polycaprolactone (PCL) for mechanical stability and electrospun into nanofibers. Islets had no detectable function ex vivo following 5 days or 12 h of subcutaneous implantation within our engineered device. Subsequently, we explored a preconditioning scheme in which islets are transplanted 2 weeks after FTY720‐loaded nanofibers are implanted. This allows FTY720 to orchestrate a local regenerative milieu while preventing premature transplantation into avascular sites that contain high concentrations of FTY720. These results provide a foundation and motivation for further investigation into the use of FTY720 in preconditioning sites for efficacious islet transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 555–568, 2018.
Clinical Features of 24 Patients With Rebound‐Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases
Authors: Anastasilakis Athanasios D , Polyzos Stergios A , Makras Polyzois , Aubry‐Rozier Berengere , Kaouri Stella , Lamy Olivier
Published: February 2017

We aimed to study the clinical and imaging characteristics of patients sustaining vertebral fractures after denosumab discontinuation. For this purpose, we conducted a computerized advanced literature search that identified 13 published cases, and we additionally included another 11 new cases from our centers. Twenty‐four postmenopausal women with vertebral fracture(s) after denosumab discontinuation, experiencing 112 fractures in total, were analyzed. The mean number of fractures per patient was 4.7. The most commonly affected vertebrae were T12 and L1. All fractures occurred 8 to 16 months after the last denosumab injection. Eighty‐three percent of the patients were treatment naïve, whereas 33% had prevalent vertebral fractures. Five (23%) patients were on concurrent aromatase inhibitor treatment. When patients were divided according to treatment duration with an arbitrary cut‐off of 2 years, those with ≤2 years of denosumab treatment had fewer fractures compared with those with >2 years (mean ± SEM fractures 3.2 ± 0.7 versus 5.2 ± 1.4, p = 0.055). Vertebroplasty was used in 5 patients, resulting in additional clinical vertebral fractures in all cases. We conclude that vertebral fracture(s) after denosumab discontinuation are in the majority of patients multiples, and they occur a few months after the effect of the last dose is depleted. Therefore, patients should not delay or omit denosumab doses. Fractures are typically osteoporotic, located at the lower thoracic and the upper lumbar spine. Vertebroplasty is an unsuccessful treatment strategy for such patients. © 2017 American Society for Bone and Mineral Research.
Extensive Remineralization of Large Pelvic Lytic Lesions Following Total Therapy Treatment in Patients With Multiple Myeloma
Authors: Mohan Meera , Samant Rohan S , Yoon Donghoon , Buros Amy F , Branca Antonio , Montgomery Corey O , Nicholas Richard , Suva Larry J , Morello Roy , Thanendrarajan Sharmilan , Schinke Carolina , Yaccoby Shmuel , van Rhee Frits , Davies Faith E , Morgan Gareth J , Zangari Maurizio
Published: February 2017

Osteolytic bone lesions are a hallmark of multiple myeloma (MM) bone disease. Bone destruction is associated with severely imbalanced bone remodeling, secondary to increased osteoclastogenesis and significant osteoblast suppression. Lytic lesions of the pelvis are relatively common in MM patients and are known to contribute to the increased morbidity because of the high risk of fracture, which frequently demands extensive surgical intervention. After observing unexpected radiological improvement in serial large pelvic CT assessment in a patient treated in a total therapy protocol, the radiographic changes of pelvic osteolytic lesions by PET/CT scanning in patients who received Total Therapy 4 (TT4) treatment for myeloma were retrospectively analyzed. Sixty‐two (62) patients with lytic pelvic lesions >1 cm in diameter were identified at baseline PET/CT scanning. Follow‐up CT studies showed that 27 of 62 patients (43%) with large baseline pelvic lesions achieved significant reaccumulation of radiodense mineralization at the lytic cortical site. The average size of lytic lesions in which remineralization occurred was 4 cm (range, 1.3 to 10 cm). This study clearly demonstrates that mineral deposition in large pelvic lesions occurs in a significant proportion of MM patients treated with TT4, potentially affecting patient outcomes, quality of life, and future treatment strategies. © 2017 American Society for Bone and Mineral Research.
An advanced tri‐culture model to evaluate the dynamic interplay among osteoblasts, osteoclasts, and endothelial cells
Authors: Pagani Stefania , Torricelli Paola , Veronesi Francesca , Salamanna Francesca , Cepollaro Simona , Fini Milena
Published: February 2017

The dynamic metabolism and the numerous roles of bone tissue necessitate a suitable in vitro model to represent them. In order to investigate the interaction among the several cell types composing bone microenvironment, we studied a tri‐culture model including human osteoblasts (OBs), osteoclasts (OCs), and endothelial cells (HUVEC). While OBs are essential for bone deposition and OCs for bone resorption, the vasculature is necessary to provide growth factors, nutrients, and oxygen in the mature tissue. The results of this study showed a strong mutual influence between OBs, OCs, and HUVEC in term of proliferation, viability, and activity (release of ALP, Coll I, OPG, RANKL, VEGF, CTSK, TGFβ, and IL‐6). The behavior of the single cultures demonstrated to be different compared to the bi‐ or tri‐cultures and depending on the cell types involved: the coexistence of OBs and OCs stimulated the synthetic activity of both cell types, while the presence of HUVEC induced a stimulating role for OBs but mainly an inhibitory effect for OC. In addition, evidence of the effects of OBs and OCs on HUVEC is highlighted by their morphology: regular and able to “sketch” little vessels in presence of OBs, more disorganized and heterogeneous in presence of OCs. Taken together, these observations well characterize an advanced cellular model to be used as starting point for mimicking bone microenvironment in vivo, thus reducing the use of animals in the preclinical phase and offering a more reliable tool to test new and innovative biomaterials.
Melatonin‐induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence
Authors: He Bin , Yin Chao , Gong Yabin , Liu Jie , Guo Huiduo , Zhao Ruqian
Published: February 2017

Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA‐encoded genes was significantly down‐regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin‐treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up‐regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin‐induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence.