bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial
Authors: Kharasch Evan D. , Neiner Alicia , Kraus Kristin , Blood Jane , Stevens Angela , Schweiger Julia , Miller J. Philip , Lenze Eric J.
Published: November 2018

Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double‐blinded crossover in 70 adults with major depression in stable remission taking any bupropion XL 300 mg tested bioequivalence and therapeutic equivalence of available XL 300 mg products. After a 4‐week lead‐in on patients' existing bupropion, four 6‐week phases evaluated brand and three generics. Patients were uninformed of switching. Drug overencapsulation ensured blinding. There were no differences between any generic and brand, or between generics, in peak plasma concentration (Cmax) and area under the plasma concentration‐time curve over the 24‐hour dosing interval (AUC0–24) for racemic bupropion or major metabolites. All generics met formal bioequivalence criteria for bupropion and metabolites. There were no differences between generics and brand, or between generics, in depression symptoms or side effects, assessed by every 3‐week in‐person interview and daily smartphone‐based self‐report. There were no differences in patients' perceptions of bupropion products. Results show three bupropion XL 300 mg generic products are both bioequivalent and not therapeutically different from brand drug and each other.
Kinetic treatment of acoustic waves in a four‐component dusty plasma
Authors: Ahmad Mushtaq , Ahmad Zulfiqar , Farooq Muhammad , Gul Almas
Published: November 2018

A kinetic formulation is developed to investigate low‐frequency dust ion acoustic waves (DIAWs) and dust acoustic waves (DAWs) as well as numerically for a four‐component, collisionless, unmagnetized dusty plasma, using the linearized Vlasov–Poisson model for species obeying the Maxwellian distribution. In particular, the dynamics of low‐frequency DIAWs is investigated by considering two cases. In the first case, ions and positive dust particles are assumed to be dynamically adiabatic while the negative dust particles are static in the background. In second case, the ions are taken adiabatic, while both positive and negative dust particles are static in the background. For DAWs, the ions are assumed to be isothermal, while both positive and negative dust species are considered adiabatic. Electrons are assumed to be isothermal in all cases. The linear characteristics and Landau damping rates for DIAWs and DAWs are investigated with effects of the dust particle concentrations and different temperature ratios. It is noted that for higher values of positive dust concentration, DIAWs (DAWs) are less (more) damped. It is also observed that the damping rate increases (decreases) as Ti approaches Te for DIAWs (DAWs). It is worth adding here that the theoretical results presented here are supported by numerical analyses and illustrations. The relevance of the study to laboratory and cosmic plasmas is also pointed out.
Galactocele of adult male breast: A cytopathologist's perspective
Authors: Bandyopadhyay Arghya , Sen Kaushik , Chakrabarti Nirmalya , Datta Shantanu
Published: November 2018

Galactocele, although a common cytological diagnosis in females, is not previously reported as a cause of breast enlargement in adult males. Hyperprolactinemia is the principal cause of galactocele in male breast. Besides drug induced hyperprolactinemia, other anatomical lesions of hypothalamo‐pituitary region and different medical conditions like cirrhosis and chronic kidney disease are to be considered along with a full evaluation of features revealing hypogonadism in case of galactocele. Aspirated milk from the male breast is the primary clue for this detailed investigation process. Here we are presenting the first case of galactocele of the male breast due to hypogonadotropic hypogonadism with idiopathic hyperprolactinemia.
Paternal methyl donor deficient diets during development affect male offspring behavior and memory‐related gene expression in mice
Authors: Sahara Yuji , Matsuzawa Daisuke , Ishii Daisuke , Fuchida Takahiro , Goto Takashi , Sutoh Chihiro , Shimizu Eiji
Published: November 2018

It has become increasingly evident that the methylation of DNA, known as an epigenetic marker, affects behavior in animals. In our previous study, a methyl‐donors (folate, methionine, and choline)‐deficient (FMCD) diet during the juvenile period could be shown to affect anxiety‐like behavior and fear memory, accompanied by alteration in some gene expression and their methylations in the hippocampus. One question is whether the fear memory of a parent affects the fear responses of offspring. To explore this question in the present study, C57BL/6 J male (F0) mice were given a FMCD diet from 3 to 12 weeks of age. After confirming the effect of the FMCD diet on the behavior and gene expression of F0 mice, their male offspring (F1‐FMCD mice) were examined using the same behavioral batteries and genetic analysis. F0 diet‐based differences in F1 behavior were observed, accompanied by the differences in the expression of memory‐related genes (Camk2α and PP1) and promoter methylation of the PP1 gene in the hippocampus. Our results add evidence that behavior and gene expression of the F1 generation could be altered due to differences in the father's intake of methyl‐donor nutrients.
Connection between gut microbiome and brain development in preterm infants
Authors: Lu Jing , Claud Erika C.
Published: November 2018

Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes. In this review, we will first discuss the factors affecting the assembly of neonatal gut microbiota and the contribution of dysbiosis in preterm infants to neuroinflammation and neurodevelopmental disorders. We then will discuss the emerging pathways connecting the gut microbiome and brain development. Further we will discuss the significance of current models for alteration of the gut microbiome (including humanized gnotobiotic models and exposure to antibiotics) to brain development and functions. Understanding the role of early optimization of the microbiome in brain development is of paramount importance for developing microbiome‐targeted therapies and protecting infants from prematurity‐related neurodevelopmental diseases.
Ensemble approach for potential habitat mapping of invasive Prosopis spp. in Turkana, Kenya
Authors: Ng Wai‐Tim , Cândido de Oliveira Silva Alexsandro , Rima Purity , Atzberger Clement , Immitzer Markus
Published: November 2018

Aim

Prosopis spp. are an invasive alien plant species native to the Americas and well adapted to thrive in arid environments. In Kenya, several remote‐sensing studies conclude that the genus is well established throughout the country and is rapidly invading new areas. This research aims to model the potential habitat of Prosopis spp. by using an ensemble model consisting of four species distribution models. Furthermore, environmental and expert knowledge‐based variables are assessed.

Location

Turkana County, Kenya.

Methods

We collected and assessed a large number of environmental and expert knowledge‐based variables through variable correlation, collinearity, and bias tests. The variables were used for an ensemble model consisting of four species distribution models: (a) logistic regression, (b) maximum entropy, (c) random forest, and (d) Bayesian networks. The models were evaluated through a block cross‐validation providing statistical measures.

Results

The best predictors for Prosopis spp. habitat are distance from water and built‐up areas, soil type, elevation, lithology, and temperature seasonality. All species distribution models achieved high accuracies while the ensemble model achieved the highest scores. Highly and moderately suitable Prosopis spp. habitat covers 6% and 9% of the study area, respectively.

Main conclusions

Both ensemble and individual models predict a high risk of continued invasion, confirming local observations and conceptions. Findings are valuable to stakeholders for managing invaded area, protecting areas at risk, and to raise awareness.
Echocardiographic diastolic function evolution in patients with an anterior Q‐wave myocardial infarction: insights from the REVE‐2 study
Authors: Ferreira João Pedro , Bauters Christophe , Eschalier Romain , Lamiral Zohra , Fay Renaud , Huttin Olivier , Girerd Nicolas , Zannad Faiez , Pinet Florence , Rossignol Patrick
Published: November 2018

Aims

Myocardial fibrosis plays a key role in the development of adverse left ventricular remodelling after myocardial infarction (MI). This study aimed to determine whether the circulating levels of BNP, collagen peptides, and galectin‐3 are associated with diastolic function evolution (both deterioration and improvement) at 1 year after an anterior MI.

Methods and results

The REVE‐2 is a prospective multicentre study including 246 patients with a first anterior Q‐wave MI. Echocardiographic assessment was performed at hospital discharge and ±1 year after MI. BNP, galectin‐3, and collagen peptides were measured ±1 month after MI. Left ventricular diastolic dysfunction (DD) was defined according to the presence of at least two criteria of echocardiographic parameters: septal e′ < 8 cm/s, lateral e′ < 10 cm/s, and left atrial volume ≥ 34 mL/m2. At baseline, 87 (35.4%) patients had normal diastolic function and 159 (64.6%) patients had DD. Follow‐up of 61 patients among the 87 patients with normal diastolic function at baseline showed that 22 patients (36%) developed DD at 1 year post‐MI. The circulating levels of amino‐terminal propeptide of type III procollagen > 6 mg/L [odds ratio (OR) = 5.29; 95% confidence interval (CI) = 1.05–26.66; P = 0.044], galectin‐3 > 13 μg/L (OR = 5.99; 95% CI = 1.18–30.45; P = 0.031), and BNP > 82 ng/L (OR = 10.25; 95% CI = 2.36–44.50; P = 0.002) quantified at 1 month post‐MI were independently associated with 1 year DD. Follow‐up of the 137 patients with DD at baseline among the 159 patients showed that 36 patients (26%) had a normalized diastolic function at 1 year post‐MI. Patients with a BNP > 82 ng/L were less likely to improve diastolic function (OR = 0.06; 95% CI = 0.01–0.28; P = 0.0003).

Conclusions

The present study suggests that circulating levels of amino‐terminal propeptide of type III procollagen, galectin‐3, and BNP may be independently associated with new‐onset DD in post‐MI patients.
On the Stability of Disubstituted Cyclobutenes – A Computational Study
Authors: Maryasin Boris , Maulide Nuno
Published: November 2018

A computational study of the electrocyclic ring‐opening of 2‐substituted cyclobutenecarboxylic acids is presented. Detailed calculations suggest a model to predict whether the product of nucleophilic alkylation of a bicyclic lactone electrophile will be a cyclobutenecarboxylic acid or its dienoic acid isomer, based on the used nucleophile.
3‐Bromo N‐Alkyl Cyanamides as Versatile Building Blocks
Authors: Wright Karen , Drouillat Bruno , Menguy Laurence , Marrot Jérôme , Couty François
Published: November 2018

3‐Bromo N‐alkyl cyanamides are accessible in one simple synthetic operation from N‐alkyl azetidines reacting with cyanogen bromide. These unexplored building blocks combine two extremely useful electrophilic moieties: an alkyl bromide and a cyanamide. We demonstrate herein that they can be transformed into a range of nitrogen‐containing molecules, and especially cyclic guanidines, accessible in enantiomerically pure form. Considering the large structural diversity of available azetidines, this contribution complements the use of these strained heterocycles in diversity‐oriented synthesis.
Stereoselective Chemoenzymatic Cascade Synthesis of the bis‐THF Core of Acetogenins
Authors: van Lint Matthijs J. , Hall Mélanie , Faber Kurt , van Spanning Rob J. M. , Ruijter Eelco , Orru Romano V. A.
Published: November 2018

bis‐Tetrahydrofuran acetogenins are a class of natural products displaying highly potent and selective anti‐tumor activity. Herein we report a new route to precursors of these natural products, utilizing the pseudo C2‐symmetry in the central bis‐tetrahydrofuran fragment. Key steps of our stereoselective chemoenzymatic strategy include the epoxide hydrolase‐mediated desymmetrization of meso‐epoxides and a cascade cyclization in either “inside‐out” or “outside‐in” direction, providing stereoselective access to the cores of both bullatacin‐ and rolliniastatin 1‐type acetogenins with 6 stereocenters each from a common mono‐epoxide precursor.
Uncertainty in quantitative analyses of topographic change: error propagation and the role of thresholding
Authors: Anderson Scott W.
Published: November 2018

Topographic surveys inevitably contain error, introducing uncertainty into estimates of volumetric or mean change based on the differencing of repeated surveys. In the geomorphic community, uncertainty has often been framed as a problem of separating out real change from apparent change due purely to error, and addressed by removing measured change considered indistinguishable from random noise from analyses (thresholding). Thresholding is important when quantifying gross changes (i.e. total erosion or total deposition), which are systematically biased by random errors in stable parts of a landscape. However, net change estimates are not substantially influenced by those same random errors, and the use of thresholds results in inherently biased, and potentially misleading, estimates of net change and uncertainty. More generally, thresholding is unrelated to the important process of propagating uncertainty in order to place uncertainty bounds around final estimates. Error propagation methods for uncorrelated, correlated, and systematic errors are presented. Those equations demonstrate that uncertainties in modern net change analyses, as well as in gross change analyses using reasonable thresholds, are likely to be dominated by low‐magnitude but highly correlated or systematic errors, even after careful attempts to reduce those errors. In contrast, random errors with little to no correlation largely cancel to negligible levels when averaged or summed. Propagated uncertainty is then typically insensitive to the precision of individual measurements, and is instead defined by the relative mean error (accuracy) over the area of interest. Given that real‐world mean elevation changes in many landscape settings are often similar in magnitude to potential mean errors in repeat topographic analyses, reducing highly correlated or systematic errors will be central to obtaining accurate change estimates, while placing uncertainty bounds around those results provides essential context for their interpretation. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Effect of complementary foods fortified with Moringa oleifera leaf powder on hemoglobin concentration and growth of infants in the Eastern Region of Ghana
Authors: Boateng Laurene , Quarpong Wilhemina , Ohemeng Agartha , Asante Matilda , Steiner‐Asiedu Matilda
Published: November 2018

Complementary foods that are deficient in both macronutrients and micronutrients coupled with a high burden of infections during the complementary feeding period are major underlying causes of child malnutrition in developing countries. Among the recent efforts to combat malnutrition by improving the quality of complementary foods in the developing world is the use of Moringa oleifera leaf powder (MLP) as a food fortificant. We conducted a randomized controlled trial to test the effect of feeding MLP‐fortified complementary food on hemoglobin concentration and growth of infants and young children after 4 months of feeding. Infants aged 8–12 months were randomly assigned to receive one of three study foods; Weanimix a cereal‐legume blend formulated with Moringa (MCL‐35g), MLP sprinkled on infants’ usual complementary foods (MS‐5g) and the control food Weanimix without Moringa (CF‐35g). Blood samples for hemoglobin determination as well as dietary intake and anthropometric data were collected at baseline and endline for 237 infants who completed the study. Data analysis was performed with SPSS (version 20) and comparisons were done by analysis of covariance (ANCOVA). There were no significant differences in hemoglobin concentration or growth indicators at endline between the three study groups. Findings of this study indicated that feeding infants a 5 g daily dose of MLP, either as part of a cereal‐legume blend or as a supplement which was sprinkled on infants’ usual complementary foods for 4 months, did not significantly improve infants’ hemoglobin concentration or growth indicators.
Region‐specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats
Authors: Duarte Joana Mendes , Gaspar Rita , Caetano Liliana , Patrício Patrícia , Soares‐Cunha Carina , Mateus‐Pinheiro António , Alves Nuno Dinis , Santos Ana Rita , Ferreira Samira G , Sardinha Vanessa , Oliveira João Filipe , Fontes‐Ribeiro Carlos , Sousa Nuno , Cunha Rodrigo A. , Ambrósio António F. , Pinto Luísa , Rodrigues Ana João , Gomes Catarina A.
Published: November 2018

Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender‐specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety‐related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC‐dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper‐ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A2A receptors (A2AR), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety‐like behavior. Notably, A2AR blockade rectified both microglia morphology in the dHIP and the lack of mPFC‐dHIP synchronization, further heralding their role in cognitive function.
A potential mechanism of the onset of acute eosinophilic pneumonia triggered by an anti‐PD‐1 immune checkpoint antibody in a lung cancer patient
Authors: Jodai Takayuki , Yoshida Chieko , Sato Ryo , Kakiuchi Yosuke , Sato Nahoko , Iyama Shinji , Kimura Tomoko , Saruwatari Koichi , Saeki Sho , Ichiyasu Hidenori , Fujii Kazuhiko , Tomita Yusuke
Published: November 2018

Introduction

The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death‐ligand 2 (PD‐L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo‐responsive Th2 cells via the PD‐1/PD‐L2 inhibitory pathway in lung could be reawaken by PD‐1 blockade therapy.

Methods

We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2‐associated pulmonary disease, triggered by nivolumab, an anti‐PD‐1 antibody, in an advanced non‐small cell lung cancer patient. Based on the current case report and literature, the present study proposes a potential mechanism of the onset of AEP as an immune‐related adverse event (irAE).

Results

A 62‐year‐old man was diagnosed with lung adenocarcinoma and nivolumab was selected as the third‐line regimen. After three cycles of nivolumab treatment, chest computed tomography revealed pulmonary infiltrates in both lungs. The patient was diagnosed with AEP based on the diagnostic criteria for AEP. Nivolumab was suspended and the patient was started on oral prednisolone. His symptoms and radiological findings had rapidly improved.

Conclusions

Given the increasing frequency of the use of anti‐PD‐1 antibodies, clinicians should be aware of the risk of AEP as a potential irAE. This study may improve our understanding of the pathophysiology underlying Th2‐associated irAEs and AEP.
Teaching a perspective‐taking component skill to children with autism in the natural environment
Authors: Welsh Fernanda , Najdowski Adel C. , Strauss Danielle , Gallegos Lindabeth , Fullen Jesse A.
Published: November 2018

We evaluated procedures for teaching three children diagnosed with autism spectrum disorder the perspective‐taking component skill of tacting what others are sensing across all five senses: see, taste, feel, hear, and smell. Using a multiple baseline across participants design, we evaluated a training package consisting of multiple exemplar training, reinforcement, and error correction. The treatment package was implemented in the natural environment and was effective for teaching participants to tact what others sensed. Generalization across untrained stimuli and people was observed from baseline to posttraining for all participants. We discuss how this component skill may be related to teaching further skills related to perspective taking such as tacting what others know, predicting future behavior based upon one's beliefs, and creating false beliefs in others for the purpose of adaptive deceptive behaviors such as keeping secrets, surprises, and bluffing during games.
Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays
Authors: Carnizello Andréa P. , Alves Jacqueline M. , Pereira Daiane E. , Campos Jacqueline C. L. , Barbosa Marília I. F. , Batista Alzir A. , Tavares Denise C.
Published: November 2018

Considering the promising previous results of ct‐[RuCl(CO)(dppb)(bipy)]PF6 (where dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. The genotoxicity of the compound was evaluated by the in vitro micronucleus test (V79, Chinese hamster lung fibroblasts; HepG2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (Swiss mice). The animals were treated with 0.63, 1.25, 2.5 and 5.0 mg/kg body weight (bw) of the compound. Negative (water) and positive (cisplatin, 1.5 mg/kg bw; methyl methanesulfonate, 40 mg/kg bw) controls were included. The parameters considered in the comet assay were the percentage of tail DNA, tail moment and tail length. The results of the in vitro micronucleus tests showed the absence of genotoxicity in V79 cells, while the compound was genotoxic in HepG2 cells at a concentration of 1.25 μm. In the in vivo micronucleus test, the compound was not genotoxic at the different doses evaluated. In the comet assay, only the dose of 5.0 mg/kg bw resulted in a significant increase in the frequency of DNA damage in hepatocytes when compared to the negative control. The genotoxic effect observed in HepG2 cells and in the liver comet assay indicates that the compound was metabolized by hepatic cells.
Cartilage/bone interface fabricated under perfusion: Spatially organized commitment of adipose‐derived stem cells without medium supplementation
Authors: Baumgartner Walter , Otto Lukas , Hess Samuel C. , Stark Wendelin J. , Märsmann Sonja , Bürgisser Gabriella Meier , Calcagni Maurizio , Cinelli Paolo , Buschmann Johanna
Published: November 2018

Tissue engineering of an osteochondral interface demands for a gradual transition of chondrocyte‐ to osteoblast‐prevailing tissue. If stem cells are used as a single cell source, an appropriate cue to trigger the desired differentiation is the use of composite materials with different amounts of calcium phosphate. Electrospun meshes of poly‐lactic‐co‐glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) in weight ratios of 100:0; 90:10, 80:20, and 70:30 were seeded with human adipose‐derived stem cells (ASCs) and cultured in DMEM without chemical supplementation. After 2 weeks of static cultivation, they were either further cultivated statically for another 2 weeks (group 1), or placed in a Bose® bioreactor with a flow rate per area of 0.16 mL cm−2 min−1 (group 2). Markers for stem cell criteria, chondrogenesis, osteogenesis, adipogenesis and angiogenesis were analyzed by quantitative real‐time PCR. Cell distribution, Sox9 protein expression and proteoglycans were assessed by histology. In group 2 (perfusion culture), chondrogenic Sox9 was upregulated toward the cartilage‐mimicking side compared to pure PLGA. On the bone‐mimicking side, Sox9 experienced a downregulation, which was confirmed on the protein level. Vice versa, expression of osteocalcin was upregulated on the bone‐mimicking side, while it was unchanged on the cartilage‐mimicking side. In group 1 (static culture), CD31 was upregulated in the presence of aCaP compared to pure PLGA, whereas Sox9 and osteocalcin expression were not affected. aCaP nanoparticles incorporated in electrospun PLGA drive the differentiation behavior of human ASCs in a dose‐dependent manner. Discrete gradients of aCaP may act as promising osteochondral interfaces. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1833–1843, 2019.
Characteristics of Self-Reported Sleep and the Risk of Falls and Fractures: The Women's Health Initiative (WHI)
Authors: Cauley Jane A , Hovey Kathleen M , Stone Katie L , Andrews Chris A , Barbour Kamil E , Hale Lauren , Jackson Rebecca D , Johnson Karen C , LeBlanc Erin S , Li Wenjun , Zaslavsky Oleg , Ochs-Balcom Heather , Wactawski-Wende Jean , Crandall Carolyn J
Published: November 2018

Sleep disturbances are common and may influence falls and fracture directly by influencing bone turnover and muscle strength or indirectly through high comorbidity or poor physical function. To investigate the association between self-reported sleep and falls and fractures, we prospectively studied 157,306 women in the Women's Health Initiative (WHI) using information on sleep quality, sleep duration, and insomnia from questionnaires. Annual self-report of falling two or more times (ie, “recurrent falling”) during each year of follow-up was modeled with repeated measures logistic regression models fit by generalized estimating equations. Cox proportional hazards models were used to investigate sleep disturbance and time to first fracture. We examined the risks of recurrent falls and fracture by sleep duration with 7 hours as referent. We examined the risks across categories of sleep disturbance, insomnia status, and sleep quality. The average follow-up time was 7.6 years for falls and 12.0 years for fractures. In multivariable adjusted models, including adjustment for comorbidity, medications, and physical function, women who were short (≤5 hours) and long (≥10 hours) sleepers had increased odds of recurrent falls (odds ratio [OR] 1.28; 95% confidence interval [CI], 1.23 to 1.34 and OR 1.25; 95% CI, 1.09 to 1.43, respectively). Poor sleep quality, insomnia, and more sleep disturbances were also associated with an increased odds of recurrent falls. Short sleep was associated with an increased risk of all fractures, and upper limb, lower limb, and central body fractures, but not hip fractures, with hazard ratios ranging from 1.10 to 1.13 (p < 0.05). There was little association between other sleep characteristics and fracture. In conclusion, short and long sleep duration and poor sleep quality were independently associated with increased odds of recurrent falls. Short sleep was associated with modest increase in fractures. Future long-term trials of sleep interventions should include falls and fractures as endpoints. © 2018 American Society for Bone and Mineral Research.
GARLEEK: Adding an extra flavor to ONIOM
Authors: Pedregal Jaime Rodríguez‐Guerra , Funes‐Ardoiz Ignacio , Sciortino Giuseppe , Sánchez‐Aparicio José‐Emilio , Ujaque Gregori , Lledós Agustí , Maréchal Jean‐Didie , Maseras Feliu
Published: November 2018

The ONIOM method, developed in the group of Keiji Morokuma, is one of the most successful examples of quantum mechanics/molecular mechanics (QM/MM) treatments, and of multilayer methods in general. Its implementation in the Gaussian program package is in particular widely used. This implementation has access to the wide variety of QM methods available in Gaussian, but is limited to only three specific force fields. The current article presents the GARLEEK interface, which expands the availability of molecular mechanics methods to the wide variety of force fields available in MM packages. The focus is in the simple installation and use. Two examples of the performance of the interface with selected systems are provided. GARLEEK is MIT‐licensed and freely available at https://github.com/insilichem/garleek. © 2018 Wiley Periodicals, Inc.
Enhancement of activity and reusability of lipase immobilized on magnetic mesoporous silica for the resolution of racemic secondary alcohols
Authors: Xue Ping , Hu Chun‐Miao , Yan Xiang‐Hui , Fang Guo‐Li , Shen Hong‐Fang
Published: November 2018

Magnetic mesoporous silica (MMS) composites with an average mesopore size (~2.98 nm), large surface area (404–442 m2/g), and high saturated magnetization (17.7–33.5 emu/g) were successfully prepared by hydrothermal crystallization in the presence of monodisperse Fe3O4 microspheres. The as‐synthesized composites served as supports for lipase from Burkholderia cepacia (BCL) immobilization in isooctane via interfacial activation and were then employed as biocatalysts for the transesterification resolution of racemic aromatic secondary alcohols to synthesize chiral intermediates. The catalytic performance of the immobilized BCL (BCL/MMS) was notably improved compared to that of the non‐immobilized BCL, with the total conversion and enantiomeric excess reaching 50 and 99% of the maximum theoretical values, respectively. Furthermore, the magnetic BCL/MMS possessing the same textural properties and enzyme loading exhibited decreasing catalytic capability as their saturated magnetization value increased. Moreover, BCL/MMS could also be readily recycled from the reaction system by applying an external magnetic field so as to facilitate its reuse up to five cycles with retaining up to 90% of the initial activity. Its high activity, easy recovery, and excellent operational stability make the BCL/MMS a potential green catalyst for the synthesis of optically active intermediates.
Amantadine‐functionalized magnetic microspheres and stable isotope labeled internal standards for reducing matrix effect in determination of five opium alkaloids by liquid chromatography‐quadrupole linear ion trap mass spectrometry
Authors: Xu Fei , Liu Feng , Wang Chaozhan , Wei Yinmao
Published: November 2018

Amantadine‐functionalized magnetic microspheres (Fe3O4@SiO2@ADME) were prepared and applied as magnetic solid‐phase extraction (MSPE) adsorbents for the enrichment and analysis of five opium alkaloids in hotpot seasoning samples with liquid chromatography coupled to quadrupole linear ion trap mass spectrometry (LC‐QqQLIT‐MS/MS). The adsorbents could strongly adsorb the opium alkaloids via hydrogen‐bonding, hydrophobic, and π–π conjugation effects. The established MSPE, combined with stable isotope‐labeled internal standards could reduce the matrix effect significantly. In the LC‐QqQLIT‐MS/MS analysis, the precursor and product ions of the analytes were monitored quantitatively and qualitatively by the multiple reaction monitoring and enhanced product ion mode, improving the reliability of detection for real samples. Under the optimum conditions, the limits of detection and limits of quantification were found to be in the range of 0.05–0.8 μg/kg and 0.25–2.5 μg/kg, respectively, and the recoveries of all targets were in the range 80.1–115.3%, with the intra‐day and inter‐day relative standard deviations being less than 9.4 and 10.7%, respectively. Finally, the proposed method was successfully applied to the determination of illegal additives of opium alkaloids in hotpot seasoning samples.
Synthesis, anti‐proliferative activity, SAR, and kinase inhibition studies of thiazol‐2‐yl‐ substituted sulfonamide derivatives
Authors: Pawar Chandrakant D. , Chavan Sadhana L. , Pawar Umakant D. , Pansare Dattatraya N. , Deshmukh Santosh V. , Shinde Devanand B.
Published: November 2018

A series of novel thiazol‐2‐yl substituted‐1‐sulfonamide derivatives were synthesized from anilines. This involved the coupling of sulfonyl chlorides with thiazol amine to obtain the final compounds 7a–7j and 8a–8j. All synthesized compounds were screened for anticancer activity against MCF‐7, HeLa, A‐549, and Du‐145 cancer cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Preliminary bioassay suggests that most of the compounds show anti‐proliferation to different degrees, with doxorubicin used as positive control. The synthesized compounds show IC50 values in the range 2.74–8.17 μM in the different cell lines. The compounds 7d, 7e, 8a, 8d, and 8e were active compared to doxorubicin. The compounds having butyl and pantyl chains were more active than their lower and higher carbon chains and also their ring counterparts.
Association of VDR‐FokI and VDBP‐Thr420Lys polymorphisms with cervical spondylotic myelopathy: A case‐control study in the population of China
Authors: Song De‐Wei , Wu Yu‐Dong , Tian Dong‐Dong
Published: November 2018

Background

Cervical spondylotic myelopathy (CSM), a common degenerative disorder, is characterized by chronic progressive compression of the cervical spinal cord. The present case‐control study aimed to explore the potential role of VDR‐FokI and VDBP‐Thr420Lys polymorphisms in the susceptibility to CSM in the Chinese population.

Methods

The study enrolled 318 CSM patients and 282 healthy individuals whose clinical data were retrospectively analyzed. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis was used to genotype VDR‐FokI and VDBP‐Thr420Lys polymorphisms. The severity of CSM was assessed using the Japanese Orthopaedic Association (JOA) score with magnetic resonance imaging (MRI) of cervical vertebra. A nonconditional binary logistic regression model was conducted for assessing the risk factors of CSM.

Results

Patients in the CSM group had longer time duration to bend over desk working than the control group. The ff genotype and f allele frequency of VDR‐FokI were elevated in CSM patients. Elevated Ff + ff genotype and f allele frequency of VDR‐FokI might increase the risk of CSM. The VDR‐FokI polymorphism was associated with nucleus pulposus capillary invasion, necrosis, hyaline degeneration and fibrosis, genesis and hyperplasia of cartilage‐like cells, and fibrocyst in the fibrous ring. The VDR‐FokI and VDBP‐Thr420Lys genotypes conformed to Hardy‐Weinberg equilibrium which showed that VDR‐FokI and VDBP‐Thr420Lys had group representation characteristics.

Conclusion

Binary logistic regression analysis confirmed that VDR‐FokI polymorphism and the time to bend over desk working were risk factors of CSM. Our results indicate that VDR‐FokI polymorphism may be closely associated with the risk of CSM.
A low cost and input tailing method of quality control on multiple annealing, and looping‐based amplification cycles‐based whole‐genome amplification products
Authors: Chen Changyue , Li Jing , Wan JueFeng , Lu Yuan , Zhang Zhen , Xu ZengHui
Published: November 2018

Background

Single‐cell whole‐genome sequencing provides novel insights into the nature of genetic heterogeneity in normal and diseased cells. However, amplification of formalin‐fixed tissues with low cell numbers is still problematic and multiple annealing, and looping‐based amplification cycles (MALBAC) is a commonly used whole‐genome amplification (WGA) method with low cell numbers.

Methods

We developed a low‐input tailing method to evaluate the MALBAC‐based WGA from sub‐nanogram or less quantities of input DNA. The tailing method uses 2100 BioAnalyzer to evaluate the size distribution of MALBAC products, and comparing the tailing with 10380 bp.

Results

Compared with a 22 loci qPCR panel, the tailing method provided a similar WGA evaluation efficiency in 13 samples on one set of study, with lower input, cheaper cost, shorter manual time, and a clear filtering cut off. Later, we demonstrated a strong correlation between tailing size and coverage breadth in another 29 samples on two sets of assays. As a result, the tailing method showed that it could predict whether a sequence breadth achieved 70% or not with 100% accuracy on these three sets of assays. Although further studies are needed, this tailing method is expected to be used as an excellent tool to select high‐quality WGA products before library construction.

Conclusions

Our tailing method can provide a new WGA quality test to evaluate the WGA efficiency with 100% accuracy (42/42). Compared with qPCR panel, our tailing method needs lower input, cheaper cost, shorter manual time, a clear filtering cut off, and extendable high throughput as well as the same sensitivity.
Current status of treatment of type 2 diabetes mellitus in Ningbo, China
Authors: Yang Tianmeng , Zheng Rongjiong , Chen Qingmei , Mao Yushan ,   The Ningbo Clinical Research Group of Diabetes
Published: November 2018

Background

The treatment status of type 2 diabetes mellitus (T2DM) in Ningbo has not been reported in the past. To evaluate the current status of T2DM in Ningbo and provide evidence to formulate more policies, a multicenter investigation was needed.

Methods

The Ningbo Clinical Research Group of Diabetes constituted nine hospitals. Participants included 3015 patients who visited the nine hospitals from June to December 2016. General characteristics, the medication situation, the laboratory indexes in nearly 3 months consisting of glycosylated hemoglobin level (HbA1c), low‐density lipoprotein cholesterol (LDL‐C), and fasting blood glucose (FBG), and the results of ophthalmologic examination were investigated. The evaluation criteria were defined based on 2013 China guideline for T2DM.

Results

The 3015 subjects included 1685 men and 1330 women. The average age was 63.3 ± 13.0 years. The prevalence of hypertension and dyslipidemia was 58.7% and 56.7%, respectively. In the examinees, nephropathy appeared in 11.6% and retinopathy in 14.5%. More than half (50.9%) of the subjects were overweight. The achievement rate of blood pressure (BP) was 39.6% (<140/80 mm Hg), FBG was 46.0% (4.4‐7.0 mmol/L), HbA1c was 41.7% (<7.0%), and LDL‐C was 51.7% (<1.8 mmol/L; and if accompanied by CHD, <2.6).

Conclusion

Ningbo City T2DM status is not optimistic, and there is a big gap with the indicators.
Hsa_circ_0000467 promotes cancer progression and serves as a diagnostic and prognostic biomarker for gastric cancer
Authors: Lu Jun , Zhang Peng‐yang , Xie Jian‐wei , Wang Jia‐bin , Lin Jian‐xian , Chen Qi‐yue , Cao Long‐long , Huang Chang‐ming , Li Ping , Zheng Chao‐hui
Published: November 2018

Background

Emerging evidence indicates that dysregulation of circular RNAs (circRNAs) is implicated in the development of malignancies. However, the diagnostic value and functional role of circRNAs in gastric cancer (GC) remain largely elusive.

Methods

Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was performed to detect the expression of hsa_circ_0000467 in tissues, cell lines, and plasma. A receiver operating characteristic (ROC) curve was constructed to estimate the diagnostic value of hsa_circ_0000467. The association between the expression level of hsa_circ_0000467 and the clinicopathological features was analyzed. Moreover, cell functional assays were performed.

Results

Hsa_circ_0000467 was significantly upregulated in GC tissue compared to adjacent nontumor tissue (n = 51, P < 0.05). Similar results were detected in the HGC‐27, MGC‐803, AGS, NUGC‐3, GES‐1 cell lines (n = 15, P < 0.001), and in the plasma samples from GC patients (n = 20, P < 0.05). The area under the ROC curve of hsa_circ_0000467 was 0.790, which is superior to commonly used biomarkers including CEA and CA‐724. We found that the expression levels of hsa_circ_0000467 in the same patient were significantly lower after surgery (n = 20, P < 0.05). Moreover, the hsa_circ_0000467 expression level is closely associated with TNM stage. Additionally, Cox multivariate analysis showed that hsa_circ_0000467 is a novel independent prognostic factor. Furthermore, in vitro experiments demonstrated that knockdown of hsa_circ_0000467 markedly inhibited the proliferation, migration, and invasion of GC cells. Moreover, hsa_circ_0000467 silencing increased tumor apoptosis in vitro.

Conclusion

Hsa_circ_0000467 can act as a novel noninvasive biomarker for the diagnosis and prognosis of GC and may be a potential therapeutic target for GC.
Hypericum perforatum in the treatment of psychiatric and neurodegenerative disorders: Current evidence and potential mechanisms of action
Authors: Zirak Nahid , Shafiee Mojtaba , Soltani Ghasem , Mirzaei Mohammad , Sahebkar Amirhossein
Published: November 2018

Background

Psychiatric disorders are substantially associated with reduced quality of life and increased mortality. Depression and anxiety are two of the most common psychiatric disorders that often co‐occur with each other as well as with other mental health conditions. Because of the limitations of currently available antidepressant therapies, there is a need for agents with improved efficacy and less adverse effects. Hypericum perforatum, widely known as St. John's wort, is a perennial herbaceous plant most well known for its antidepressant properties.

Methods

We reviewed the available in vitro, in vivo, and clinical evidence on the efficacy, safety, and mechanisms of action of St. John's wort and its active constituents in the treatment of psychiatric and neurodegenerative disorders.

Results

Several interesting data have been reported about the antidepressant properties of H. perforatum in clinical trials with different designs. In particular, a number of antidepressant‐controlled trials demonstrated that H. perforatum and its active ingredients, hypericin and hyperforin, possess antidepressant properties similar to those of tricyclic antidepressants and selective serotonin reuptake inhibitors but with fewer and milder side effects.

Conclusion

St. John's wort may exert potent antidepressant effects and represents an efficacious and safe treatment. However, the current clinical evidence regarding the efficacy of H. perforatum in other psychiatric and neurodegenerative disorders is not sufficient to draw a robust conclusion.
Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole‐body homeostasis
Authors: Zhang Qing , Duplany Agnès , Moncollin Vincent , Mouradian Sandrine , Goillot Evelyne , Mazelin Laetitia , Gauthier Karine , Streichenberger Nathalie , Angleraux Céline , Chen Jie , Ding Shuzhe , Schaeffer Laurent , Gangloff Yann‐Gaël
Published: November 2018

Background

The protein kinase mechanistic target of rapamycin (mTOR) controls cellular growth and metabolism. Although balanced mTOR signalling is required for proper muscle homeostasis, partial mTOR inhibition by rapamycin has beneficial effects on various muscle disorders and age‐related pathologies. Besides, more potent mTOR inhibitors targeting mTOR catalytic activity have been developed and are in clinical trials. However, the physiological impact of loss of mTOR catalytic activity in skeletal muscle is currently unknown.

Methods

We have generated the mTORmKOKI mouse model in which conditional loss of mTOR is concomitant with expression of kinase inactive mTOR in skeletal muscle. We performed a comparative phenotypic and biochemical analysis of mTORmKOKI mutant animals with muscle‐specific mTOR knockout (mTORmKO) littermates.

Results

In striking contrast with mTORmKO littermates, mTORmKOKI mice developed an early onset rapidly progressive myopathy causing juvenile lethality. More than 50% mTORmKOKI mice died before 8 weeks of age, and none survived more than 12 weeks, while mTORmKO mice died around 7 months of age. The growth rate of mTORmKOKI mice declined beyond 1 week of age, and the animals showed profound alterations in body composition at 4 weeks of age. At this age, their body weight was 64% that of mTORmKO mice (P < 0.001) due to significant reduction in lean and fat mass. The mass of isolated muscles from mTORmKOKI mice was remarkably decreased by 38–56% (P < 0.001) as compared with that from mTORmKO mice. Histopathological analysis further revealed exacerbated dystrophic features and metabolic alterations in both slow/oxidative and fast/glycolytic muscles from mTORmKOKI mice. We show that the severity of the mTORmKOKI as compared with the mild mTORmKO phenotype is due to more robust suppression of muscle mTORC1 signalling leading to stronger alterations in protein synthesis, oxidative metabolism, and autophagy. This was accompanied with stronger feedback activation of PKB/Akt and dramatic down‐regulation of glycogen phosphorylase expression (0.16‐fold in tibialis anterior muscle, P < 0.01), thus causing features of glycogen storage disease type V.

Conclusions

Our study demonstrates a critical role for muscle mTOR catalytic activity in the regulation of whole‐body growth and homeostasis. We suggest that skeletal muscle targeting with mTOR catalytic inhibitors may have detrimental effects. The mTORmKOKI mutant mouse provides an animal model for the pathophysiological understanding of muscle mTOR activity inhibition as well as for mechanistic investigation of the influence of skeletal muscle perturbations on whole‐body homeostasis.
Efficient and selective adsorption of small polyols by boronic acid functionalized polystyrene adsorbent
Authors: Jia Yu‐Xiang , Sun Weizhi , Yin Chai , Xu Chao , Yu Shitao , Mo Xian
Published: November 2018

BACKGROUND

The separation of polyols from fermentation broth remains a challenge due to their high boiling points and strong hydrophilicity, however, they show pH‐dependent reversible interaction with boronic acid, which makes it a perfect moiety for the construction of functional adsorbents for polyols enrichment.

RESULTS

Boronic acid functionalized polystyrene adsorbents were successfully synthesized by loading N‐ or O‐substituted phenylboronic acid into chloromethylated polystyrene resin. Aminophenyl boronic acid modified resin exhibits the best adsorption capacities, 0.34 mmol g−1 for glycerol and 0.27 mmol g−1 for 1,2,4‐butanetriol in aqueous solution, whereas the adsorption capacities of most commercial resins are below 0.07 mmol g−1. The adsorption capacity increased with increasing alkalinity and the boronic ester dissociates when subjected to acidic conditions. The reversible interaction facilitates regeneration of the adsorbent, and the resin displayed good adsorption stability during six reuses.

CONCLUSION

The functional resin displays great adsorption advantage over commercial resins and adsorptive preference for 1,2‐ and 1,3‐polyols rather than 1,4‐polyol in double‐adsorbate systems, distinctive from commercial resin whose adsorption capacity is mainly determined by the hydrophilicity of the adsorbate. Thus, boronic acid functionalized polystyrene adsorbent is a potential adsorbent for polyol enrichment from fermentation. © 2018 Society of Chemical Industry