bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulsed electromagnetic field at different stages of knee osteoarthritis in rats induced by low‐dose monosodium iodoacetate: Effect on subchondral trabecular bone microarchitecture and cartilage degradation
Authors: Yang Xiaotian , He Hongchen , Zhou Yuan , Zhou Yujing , Gao Qiang , Wang Pu , He Chengqi
Published: December 2016

The aim of the study was to investigate the efficacy of pre‐emptive, early, and delayed pulsed electromagnetic field (PEMF) treatment on cartilage and subchondral trabecular bone in knee osteoarthritis (OA) rats induced by low‐dose monosodium iodoacetate (MIA). Seventy‐five 12‐week‐old male Sprague–Dawley rats were assigned to five groups: OA (n = 30), pre‐emptive PEMF (n = 10), early PEMF (n = 10), delayed PEMF (n = 10), and control (n = 15). Osteoarthritis was induced by injecting 0.2 mg MIA in rat's right knee joint. Control rats received a single sterile saline injection in the right knee. Male rats received pre‐emptive (n = 10, day 0‐end of week 4), early (n = 10, end of week 4‐end of week 8), or delayed (n = 10, end of week 8‐end of week 12) PEMF treatment (75 Hz, 1.6 mT). After 4, 8, and 12 weeks, rats were sacrificed at each time point and right knees were harvested. After sacrifice, micro‐computed tomography, histology, and biomarker analyses were performed. We found pre‐emptive PEMF treatment preserved subchondral trabecular bone microarchitecture and prevented subchondral bone loss in MIA‐induced OA rat model. Early and delayed PEMF treatment maintained subchondral trabeculae. PEMF treatment increased bone and cartilage formation, and decreased bone and cartilage resorption. Pre‐emptive and early PEMF treatment had moderate effects on cartilage degradation. Time point of treatment initiation is crucial for treating OA. PEMF might become a potential biophysical treatment modality for osteoarthritis. Bioelectromagnetics. 38:227–238, 2017. © 2016 Wiley Periodicals, Inc.
tRNA biology in the omics era: Stress signalling dynamics and cancer progression
Authors: Orioli Andrea
Published: December 2016

Recent years have seen a burst in the number of studies investigating tRNA biology. With the transition from a gene‐centred to a genome‐centred perspective, tRNAs and other RNA polymerase III transcripts surfaced as active regulators of normal cell physiology and disease. Novel strategies removing some of the hurdles that prevent quantitative tRNA profiling revealed that the differential exploitation of the tRNA pool critically affects the ability of the cell to balance protein homeostasis during normal and stress conditions. Furthermore, growing evidence indicates that the adaptation of tRNA synthesis to cellular dynamics can influence translation and mRNA stability to drive carcinogenesis and other pathological disorders. This review explores the contribution given by genomics, transcriptomics and epitranscriptomics to the discovery of emerging tRNA functions, and gives insights into some of the technical challenges that still limit our understanding of the RNA polymerase III transcriptional machinery.
MAMs are attractive targets for bacterial repurposing of the host cell
Authors: Escoll Pedro , Rolando Monica , Buchrieser Carmen
Published: December 2016

Pathogenic bacteria frequently target the endoplasmic reticulum (ER) and mitochondria in order to exploit host functions. ER‐mitochondria inter‐organelle communication is topologically sub‐compartmentalized at mitochondria‐associated ER membranes (MAMs). MAMs are specific membranous microdomains with unique regulatory functions such as lipid synthesis and trafficking, calcium homeostasis, mitochondrial morphology, inflammasome activation, autophagosome formation, and apoptosis. These important cellular processes are all modulated by pathogens to subvert host functions and promote infection, thus it is tempting to assume that pathogenic bacteria target MAMs to subvert these different pathways in their hosts. First lines of evidence that support this hypothesis come from Legionella pneumophila. This intracellular bacterium secretes an effector that exhibits sphingosine‐1 phosphate lyase activity (LpSpl) that seems to target MAMs to modulate the autophagy response to infection. Here we thus propose the concept that MAMs could be targeted by pathogenic bacteria to undermine key host cellular processes.
Forces positioning the mitotic spindle: Theories, and now experiments
Authors: Wu Hai‐Yin , Nazockdast Ehssan , Shelley Michael J. , Needleman Daniel J.
Published: December 2016

The position of the spindle determines the position of the cleavage plane, and is thus crucial for cell division. Although spindle positioning has been extensively studied, the underlying forces ultimately responsible for moving the spindle remain poorly understood. A recent pioneering study by Garzon‐Coral et al. uses magnetic tweezers to perform the first direct measurements of the forces involved in positioning the mitotic spindle. Combining this with molecular perturbations and geometrical effects, they use their data to argue that the forces that keep the spindle in its proper position for cell division arise from astral microtubules growing and pushing against the cell's cortex. Here, we review these ground‐breaking experiments, the various biomechanical models for spindle positioning that they seek to differentiate, and discuss new questions raised by these measurements.
Multiple confidence intervals for selected parameters adjusted for the false coverage rate in monotone dose–response microarray experiments
Authors: Peng Jianan , Liu Wei , Bretz Frank , Shkedy Ziv
Published: December 2016

Benjamini and Yekutieli () introduced the concept of the false coverage‐statement rate (FCR) to account for selection when the confidence intervals (CIs) are constructed only for the selected parameters. Dose–response analysis in dose–response microarray experiments is conducted only for genes having monotone dose–response relationship, which is a selection problem. In this paper, we consider multiple CIs for the mean gene expression difference between the highest dose and control in monotone dose–response microarray experiments for selected parameters adjusted for the FCR. A simulation study is conducted to study the performance of the method proposed. The method is applied to a real dose–response microarray experiment with 16, 998 genes for illustration.
Acceptorless Dehydrogenation of Alcohols Catalyzed by CuIN‐Heterocycle Thiolate Complexes
Authors: Tan Da‐Wei , Li Hong‐Xi , Zhang Meng‐Juan , Yao Jian‐Lin , Lang Jian‐Ping
Published: December 2016

CuI N‐heterocycle thiolate clusters efficiently catalyze the acceptorless dehydrogenation of alcohols at 70 °C. A variety of secondary/primary benzylic, allylic, and aliphatic alcohols are dehydrogenated to the corresponding ketones and aldehydes in high yields of isolated product upon release of H2. This simple catalytic system is involved in the synthesis of imines through the one‐pot reaction of alcohols and amines.
Role of Water in Catalyzing Proton Transfer in Glucose Dehydration to 5‐Hydroxymethylfurfural
Authors: Zhou Feng , Sun Xiang , Wu Di , Zhang Yugen , Su Haibin
Published: December 2016

5‐Hydroxymethylfurfural (HMF) is one of the most important and versatile biomass‐derived platform chemicals for the synthesis of a wide range of industrial chemicals, including biofuels. HMF can be obtained by dehydration of glucose with acid catalysts. The conversion proceeds through two steps, that is, glucose–fructose isomerization and dehydration of fructose to HMF. During the first step, water plays an important role as a proton shuttle to promote the reaction and reduce the energy barriers, which results in the acceleration of the reaction. Besides, water can also block the side reaction. The role of water joining and catalyzing the reaction is further proved by experimental findings, that is, by using DMSO/D2O as solvent deuterium was found at C1 of HMF from NMR analysis.
Ruthenium–Ruthenium‐Bonded [Bis{corrolato‐ruthenium(III)}]n (n=0, +1, −1) Complexes: Model Compounds for the Photosynthetic Special Pair
Authors: Sinha Woormileela , Sommer Michael G. , Hettmanczyk Lara , Patra Bratati , Filippou Vasileios , Sarkar Biprajit , Kar Sanjib
Published: December 2016

We present herein the synthesis of three new bis(corrolato‐ruthenium(III)) complexes containing unsupported Ru–Ru bonds and their characterization in different redox states. The 1H NMR spectra of the bis(corrolato‐ruthenium(III)) complexes displayed “normal” chemical shifts and the compounds proved to be EPR‐silent. Crystallographic characterization of the dimers indicated Ru–Ru distances of 2.175 Å, consistent with a triple bond between the two ruthenium centers. All of the synthesized complexes undergo two successive reversible oxidations and a single reversible reduction. A combination of UV/Vis/NIR/EPR spectroelectrochemical studies and DFT calculations established the redox state distributions in these ruthenium–ruthenium‐bonded dimers. Whereas reduction of the dimers is metal‐based and leads to metal‐metal‐bonded mixed‐valent RuII–RuIII species, one‐electron oxidation largely retains the RuIII–RuIII situation with the generation of metal‐bound corrolato radicals. The present study thus concerns the first UV/Vis/NIR/EPR spectroelectrochemical characterization and DFT calculations of ruthenium–ruthenium‐bonded rotationally ordered corrole dimers. The mean plane separation between the two corrole units in these dimers is around 3.543 Å, which is in close agreement to that in the “special pair” in chlorophyll. Oxidation of these ruthenium–ruthenium‐bonded dimers gives rise to two new electronic absorption bands in the NIR region (similar to those of the special pair), which have apparently not been mentioned/observed in earlier reports on ruthenium–ruthenium‐bonded corrole dimers. These bands mainly originate from inter‐corrole transitions.
The contemporary value of peak creatine kinase‐MB after ST‐segment elevation myocardial infarction above other clinical and angiographic characteristics in predicting infarct size, left ventricular ejection fraction, and mortality
Authors: Hartman Minke H. T. , Eppinga Ruben N. , Vlaar Pieter J. J. , Lexis Chris P. H. , Lipsic Erik , Haeck Joost D. E. , van Veldhuisen Dirk J. , van der Horst Iwan C. C. , van der Harst Pim
Published: December 2016

Background

Complex multimarker approaches to predict outcome after ST‐elevation myocardial infarction (STEMI) have only considered a single baseline sample, while neglecting easily obtainable peak creatine kinase and creatine kinase‐MB (CK‐MB) values during hospitalization.

Methods

We studied 476 patients undergoing primary percutaneous coronary intervention for STEMI and cardiac magnetic resonance imaging (CMRI) at 4‐6 months after STEMI. We determined the association with cardiac biomarkers (peak CK‐MB, peak troponin T, N‐terminal pro‐brain natriuretic peptide), clinical and angiographic characteristics with infarct size, and LVEF, followed by association with mortality in 1120 STEMI patients.

Results

Peak CK‐MB was the strongest predictor for infarct size (P<0.001, R
2=0.60) and LVEF (P<0.001, R
2=0.40). The additional value of clinical and angiographic characteristics was limited. The optimal peak CK‐MB cutpoints, for differentiation among small (<10% of the left ventricle), moderate (≥10%–<30%), and large infarct size (≥30%), were 210 U/L and 380 U/L, respectively. These cutpoints were associated with 90‐day mortality; the hazard ratio for moderate infarct was 2.99 (95% confidence interval [CI]: 1.51‐5.93, P=0.002) and for large infarct 6.53 (95% CI: 3.63‐11.76, P<0.001).

Conclusions

Classical peak CK‐MB measured during hospitalization for STEMI was superior to other clinical and angiographic characteristics in predicting CMRI‐defined infarct size and LVEF, and should be included and validated in future multimarker studies. Peak CK‐MB cutpoints differentiated among infarct size categories and were associated with increased 90‐day mortality risk.
Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base
Authors: Pezzi Todd A. , Mohamed Abdallah S. R. , Sheu Tommy , Blanchard Pierre , Sandulache Vlad C. , Lai Stephen Y. , Cabanillas Maria E. , Williams Michelle D. , Pezzi Christopher M. , Lu Charles , Garden Adam S. , Morrison William H. , Rosenthal David I. , Fuller Clifton D. , Gunn G. Brandon
Published: December 2016

BACKGROUND

The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS).

METHODS

The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA).

RESULTS

In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose‐survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137‐1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379‐1.827), distant metastasis (HR, 1.385; 95% CI, 1.216‐1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547‐0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718‐0.988; 45‐59.9 Gy: HR, 0.596; 95% CI, 0.479‐0.743; 60‐75 Gy: HR, 0.419; 95% CI, 0.339‐0.517) correlated with OS. The RT dose‐survival correlation for patients who received higher (60‐75 Gy) versus lower (45‐59.9 Gy) therapeutic doses was confirmed by propensity‐score matching.

CONCLUSIONS

Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653–1661. © 2017 American Cancer Society.
Does hormonal therapy for fertility preservation affect the survival of young women with early‐stage endometrial cancer?
Authors: Greenwald Zoë R. , Huang Lina N. , Wissing Michel D. , Franco Eduardo L. , Gotlieb Walter H.
Published: December 2016

BACKGROUND

The incidence of endometrial cancer among young women is increasing. Some patients with low‐grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival.

METHODS

Patients with localized, low‐grade endometrial cancer who were aged <45 years were selected from the Surveillance, Epidemiology, and End Results database between 1993 and 2012. Propensity score matching was used to select comparable groups receiving HT or primary surgery. Cancer‐specific and overall survival were measured using Kaplan‐Meier methods. Hazard ratios and 95% confidence intervals (95% CIs) were estimated using Cox models adjusted for age, period of diagnosis, marital status, race, tumor grade, morphology, and previous radiotherapy.

RESULTS

A total of 6339 women were included in the current study cohort, 161 of whom initially received HT and 6178 of whom received primary surgery. After 15 years of follow‐up, all‐cause mortality did not differ between the groups (HT group: 14.1% [95% CI, 6.7%‐28.4%] and propensity score‐matched primary surgery group: 9.3% [95% CI, 4.1%‐20.5%]). Cancer‐specific mortality appeared higher in patients treated with HT compared with those treated with primary surgery (9.2% [95% CI, 3.4%‐24.0%] vs 2.1% [95% CI, 1.5%‐2.8%]). However, this difference was driven by 3 late deaths in the HT group. Sensitivity analyses using a broader definition of cancer‐specific mortality provided no statistical evidence of a survival difference between the treatment groups. The hazard ratio for the overall risk of death was 1.45 (95% CI, 0.44‐4.74).

CONCLUSIONS

Based on this population‐based cohort, young patients with low‐grade endometrial cancer appear to have excellent survival, regardless of the primary therapy chosen (HT vs primary surgery). The current selection of patients for HT to preserve fertility, which is managed carefully by experienced clinicians, does not appear to significantly worsen clinical outcomes. Cancer 2017;123:1545–1554. © 2017 American Cancer Society.
Controlled Deposition and Performance Optimization of Perovskite Solar Cells Using Ultrasonic Spray‐Coating of Photoactive Layers
Authors: Chang Wei‐Chieh , Lan Ding‐Hung , Lee Kun‐Mu , Wang Xiao‐Feng , Liu Cheng‐Liang
Published: December 2016

This study investigated a new film‐deposition technique, ultrasonic spray‐coating, for use in the production of a photoactive layer of perovskite solar cells. Stable atomization and facile fabrication of perovskite thin films by ultrasonic spray‐coating were achieved in a one‐step method through manipulating the ink formulation (e.g., solution concentration, precursor composition, and mixing solvent ratio) and the drying kinetics (e.g., post‐annealing temperature). The performance of the perovskite solar cells was mainly influenced by the intrinsic film morphology and crystalline orientation of the deposited perovskite layer. By suitable optimization of the spreading and drying conditions of the ink, ultrasonic spray‐coated perovskite photovoltaic devices were obtained with a maximum power conversion efficiency of 11.30 %, a fill factor of 73.6 %, a short‐circuit current of 19.7 mA cm−1, and an open‐circuit voltage of 0.78 V, respectively. Notably, the average power efficiency reached above 10 %, attributed to the large flower‐like perovskite crystal with orientation along the (1 1 2)/(2 0 0) and (2 2 4)/(4 0 0) directions. Thus, the ultrasonic spray‐coating method for perovskite photoactive layers, combining advantages of good photovoltaic performance results and benefits from cost and processing, has the potential for large‐scale commercial production.
Robust design of CMOS amplifiers oriented to settling‐time specification
Authors: Giustolisi Gianluca , Palumbo Gaetano
Published: December 2016

In this paper, we propose a new approach for the robust design of complementary metal‐oxide‐semiconductor amplifiers based on settling‐time specifications. The approach is based on the definition of the separation factors and on the analysis of their role in the settling time. We define a design strategy for being certain that an OTA satisfies the settling‐time constraint under any statistical variation of process or design parameters. The proposed strategy is applied to the transistor level design of a two‐stage amplifier and a three‐stage one. Simulation results, in good agreement with theory, confirm the validity of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study
Authors: Plichart Matthieu , Orvoën Galdric , Jourdain Patrick , Quinquis Laurent , Coste Joël , Escande Michele , Friocourt Patrick , Paillaud Elena , Chedhomme François‐Xavier , Labourée Florian , Boully Clémence , Benetos Athanase , Domerego Jean‐Jacques , Komajda Michel , Hanon Olivier
Published: December 2016

Aims

To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients.

Methods and results

A total of 383 patients aged 80 years or older, hospitalized in geriatrics care for dyspnoea, had a BNP measurement at the acute phase. Independent cardiologists blinded to BNP values classified the patients into cardiac vs. respiratory aetiology according to the European Society of Cardiology guidelines. Mean (SD) age was 88.5 (5.4) years, 66% (n = 254) of patients were women, 62% (n = 238) had cardiac dyspnoea and 38% (n = 145) had respiratory dyspnoea. The BNP levels were significantly higher in the cardiac group (median = 385.5 ng/L, interquartile range = 174.0–842.0) than in the respiratory group (median = 172.0 ng/L, interquartile range = 70.8–428.0; P < 0.001). On its own, BNP showed poor discriminative ability [area under the curve (AUC) = 0.68; 95% confidence interval (CI) 0.62–0.73] for the diagnostic. In multivariate analysis, BNP remained independently associated with the cardiac aetiology after full‐adjustment (odds ratio 1 log increase = 1.87; 95% CI 1.28–2.74), but did not improve the discrimination between the cardiac and the respiratory aetiologies (ΔAUC = 0.013, P = 0.16). In addition, although adding BNP to the other predictive covariates yielded a significant continuous NRI of 57.8% (95% CI 31.2–83.5%), the mean changes in individual predicted probabilities were too low (<3%) to be clinically relevant.

Conclusion

In this population of very old patients with acute dyspnoea, despite being independently associated with the cardiac aetiology, BNP was not useful for better discriminating cardiac vs. respiratory origin.
Enantioselective Aromatic Sulfide Oxidation and Tandem Kinetic Resolution Using Aqueous H2O2 and Chiral Iron–Bis(oxazolinyl)bipyridine Catalysts
Authors: Jalba Angela , Régnier Noémie , Ollevier Thierry
Published: December 2016

An efficient method for the oxidation of aromatic sulfides has been developed by using aqueous H2O2, catalyzed by the in situ generated chiral Fe/6,6′‐bis(4‐isopropyloxazolin‐2‐yl)‐2,2′‐bipyridine (bipybox‐iPr) complex. The corresponding sulfoxides were obtained with high enantioselectivities (up to 98.5:1.5 er) and in good yields (up to 61 %) when the mono‐oxidation of the sulfides was performed in combination with the kinetic resolution of the sulfoxide into the sulfone.
Health Insurance Costs and Employee Compensation: Evidence from the National Compensation Survey
Authors: Anand Priyanka
Published: December 2016

This paper examines the relationship between rising health insurance costs and employee compensation. I estimate the extent to which total compensation decreases with a rise in health insurance costs and decompose these changes in compensation into adjustments in wages, non‐health fringe benefits, and employee contributions to health insurance premiums. I examine this relationship using the National Compensation Survey, a panel dataset on compensation and health insurance for a sample of establishments across the USA. I find that total hourly compensation reduces by $0.52 for each dollar increase in health insurance costs. This reduction in total compensation is primarily in the form of higher employee premium contributions, and there is no evidence of a change in wages and non‐health fringe benefits. These findings show that workers are absorbing at least part of the increase in health insurance costs through lower compensation and highlight the importance of examining total compensation, and not just wages, when examining the relationship between health insurance costs and employee compensation. Copyright © 2016 John Wiley & Sons, Ltd.
Structural Chemistry, Fuzzy Logic, and the Law
Authors: Bernstein Joel
Published: December 2016

Chemistry is generally considered to be one of the exact sciences, which implies that much of the thinking and reasoning can be governed by “always” and “never” laws and rules. However, in practice, much of chemistry involves concepts that invoke general rules with the exceptions to those rules arousing curiosity and generating new experiments and theories that facilitate the progress of chemical science. The lack of precision, in fact, requires a mode of thinking and operating that has been called “fuzzy logic”, not necessarily in a pejorative sense, but rather recognizing the fundamental nature of this experimental science and how it plays out in practice. We provide herein some examples of fuzzy logic in the practice of chemistry and demonstrate how these are manifested in the role and behavior of expert witnesses, particularly in pharmaceutical patent litigations that deal with the solid forms of active pharmaceutical ingredients.
Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15
Authors: Borner Tito , Arnold Myrtha , Ruud Johan , Breit Samuel N. , Langhans Wolfgang , Lutz Thomas A. , Blomqvist Anders , Riediger Thomas
Published: December 2016

Background

The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice.

Methods

Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response.

Results

In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake.

Conclusions

These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP‐dependent action.
Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study
Authors: Pasco Julie A. , Mohebbi Mohammadreza , Holloway Kara L. , Brennan‐Olsen Sharon L. , Hyde Natalie K. , Kotowicz Mark A.
Published: December 2016

Background

We aimed to examine the relationship between musculoskeletal deterioration and all‐cause mortality in a cohort of women studied prospectively over a decade.

Methods

A cohort of 750 women aged 50–94 years was followed for a decade after femoral neck bone mineral density (BMD) and appendicular lean mass (ALM) were measured using dual energy X‐ray absorptiometry, in conjunction with comorbidities, health behaviour data, and other clinical measures. The outcome was all‐cause mortality identified from the Australian National Deaths Index. Using Cox proportional hazards models and age as the time variable, mortality risks were estimated according to BMD groups (ideal‐BMD, osteopenia, and osteoporosis) and ALM groups (T‐scores > −1.0 high, −2.0 to −1.0 medium, <−2.0 low).

Results

During 6712 person years of follow‐up, there were 190 deaths, the proportions increasing with diminishing BMD: 10.7% (23/215) ideal‐BMD, 23.5% (89/378) osteopenia, 49.7% (78/157) osteoporosis; and with diminishing ALM: 17.0% (59/345) high, 26.2% (79/301) medium, 50.0% (52/104) low. In multivariable models adjusted for smoking, polypharmacy, and mobility, compared with those with ideal BMD, mortality risk was greater for those with osteopenia [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.11–2.81] and osteoporosis (HR 2.61, 95%CI 1.60–4.24). Similarly, compared with those with high ALM, adjusted mortality risk was greater for medium ALM (HR 1.36, 95%CI 0.97–1.91) and low ALM (HR 1.65, 95%CI 1.11–2.45). When BMD and ALM groups were tested together in the model, BMD remained a predictor of mortality (HR 1.74, 95%CI 1.09–2.78; HR 2.82, 95%CI 1.70–4.70; respectively), and low ALM had borderline significance (HR 1.52, 95%CI 1.00–2.31), which was further attenuated after adjusting for smoking, polypharmacy, and mobility.

Conclusions

Poor musculoskeletal health increased the risk for mortality independent of age. This appears to be driven mainly by a decline in bone mass. Low lean mass independently exacerbated mortality risk, and this appeared to operate through poor health exposures.
Institutional Path Dependence in Competitive Dynamics: The Case of Paper Industries in Finland and the USA
Authors: Lamberg Juha‐Antti , Laurila Juha , Nokelainen Tomi
Published: December 2016

Prior research on competitive dynamics has failed to offer tools to understand distorted patterns of competition that emerge from distinct institutional and historical contexts. Our analysis suggests that a joint effect of institutional rules, governance structures, and shared cognition plays a pivotal role in firm‐level competitive behavior and capability development. We show how globally significant market positions can result from specific institutional arrangements between firms and governments, especially if coupled with interfirm contractual commitments. Our results call for more attention to these interfirm commitments that are built on formal rules and governmental support, but whose impact they yet exceed. Copyright © 2016 John Wiley & Sons, Ltd.
A de novo splice site mutation in EHMT1 resulting in Kleefstra syndrome with pharmacogenomics screening and behavior therapy for regressive behaviors
Authors: Mitra Amit Kumar , Dodge Jessica , Van Ness Jody , Sokeye Israel , Van Ness Brian
Published: December 2016

Background

Kleefstra syndrome (KS) is a rare autosomal dominant developmental disability, caused by microdeletions or intragenic mutations within the epigenetic regulator gene EHMT1 (euchromatic histone lysine N‐methyltransferase 1). In addition to common features of autism, young adult regressive behaviors have been reported. However, the genetic downstream effects of the reported deletions or mutations on KS phenotype have not yet been completely explored. While genetic backgrounds affecting drug metabolism can have a profound effect on therapeutic interventions, pharmacogenomic variations are seldom considered in directing psychotropic therapies.

Methods

In this report, we used next‐generation sequencing (exome sequencing and high‐throughput RNA sequencing) in a patient and his parents to identify causative genetic variants followed by pharmacogenomics‐guided clinical decision‐making for making positive changes toward his treatment strategies. The patient had an early autism diagnosis and showed significant regressive behaviors and physical aberrations at age 23.

Results

Exome sequencing identified a novel, de novo splice site variant NM_024757.4: c.2750‐1G>T in EHMT1, a candidate gene for Kleefstra syndrome, in the patient that results in exon skipping and downstream frameshift and termination. Gene expression results from the patient showed, when compared to his parents, there was a significant decreased expression of several reported gene variants associated with autism risk. Further, using a pharmacogenomics genotyping panel, we discovered that the patient had the CYP2D6 nonfunctioning variant genotype *4/*4 that results in very low metabolic activity on a number of psychotropic drugs, including fluvoxamine which he was prescribed. As reported here, a change in psychotropic drugs and intense behavior therapies resulted in a significant reversal of the regressive behaviors and physical aberrations.

Conclusion

These results demonstrate an individualized approach that integrated genetic information and behavior therapies, resulting in a dramatic improvement in regressive behaviors associated with KS.
Accurate measurement of JHH in overlapped signals by a TOCSY‐edited SERF Experiment
Authors: Fredi André , Nolis Pau , Parella Teodor
Published: December 2016

Selective refocusing (GSERF or the recent PSYCHEDELIC) experiments were originally designed to determine all proton–proton coupling constants (JHH) for a selected proton resonance. They work for isolated signals on which selective excitation can be successfully applied but, as it happens in other selective experiments, fail for overlapped signals. To circumvent this limitation, a doubly‐selective TOCSY‐GSERF scheme is presented for the measurement of JHH in protons resonating in crowded regions. This new experiment takes advantage of the editing features of an initial TOCSY transfer to uncover hidden resonances that become accessible to perform the subsequent frequency‐selective refocusing. Copyright © 2016 John Wiley & Sons, Ltd.
Morphometry of a Pre‐Hispanic Dog from Northwestern Argentina (AD 800–1200)
Authors: Belotti López de Medina C. R.
Published: December 2016

A detailed morphometric description of a dog skull from the pre‐Hispanic archaeological site La Isla de Tilcara (northwestern Argentina, ca AD 800–1200) is presented. The resulting data were compared with those of dog skulls from other South American archaeological sites to establish dog morphotype. The examined skull belonged to a small, long‐snouted dog, similar to the smallest morphotypes from the central Andes. Copyright © 2016 John Wiley & Sons, Ltd.
Method‐of‐use study of naltrexone sustained release (SR)/bupropion SR on body weight in individuals with obesity
Authors: Halseth Amy , Shan Kevin , Walsh Brandon , Gilder Kye , Fujioka Ken
Published: December 2016

Objective

This study assessed the effects of 32 mg naltrexone sustained release (SR)/360 mg bupropion SR (NB) on body weight in adults with obesity, with comprehensive lifestyle intervention (CLI), for 78 weeks.

Methods

In this phase 3b, randomized, open‐label, controlled study, subjects received NB + CLI or usual care (standard diet/exercise advice) for 26 weeks. NB subjects not achieving 5% weight loss at week 16 were discontinued, as indicated by product labeling. After week 26, usual care subjects began NB + CLI. Assessments continued through week 78. The primary end point was percent change in weight from baseline to week 26 in the per protocol population. Other end points included percentage of subjects achieving ≥5%, ≥10%, and ≥15% weight loss, percent change in weight at week 78, and adverse events (AEs) necessitating study medication discontinuation.

Results

NB + CLI subjects lost significantly more weight than usual care subjects at week 26 (8.52% difference; P < 0.0001). Weight loss persisted through 78 weeks. In total, 20.7% of subjects discontinued medication for AEs, including 7.0% for nausea.

Conclusions

Treatment with NB, used as indicated by prescribing information and with CLI, significantly improved weight loss over usual care alone. NB‐facilitated weight loss was sustained for 78 weeks and was deemed safe and well tolerated.
Initial body fat gain is related to brain volume changes in adolescents: A repeated‐measures voxel‐based morphometry study
Authors: Yokum Sonja , Stice Eric
Published: December 2016

Objective

Individuals with obesity versus those within a healthy weight range show brain volume differences, but it is unclear whether these differences reflect initial vulnerability factors or are secondary to weight gain.

Methods

One hundred sixty‐two adolescents (M age = 15.3 ± 1.1; 81 females) with healthy weight were scanned at baseline. Sixty subjects (M baseline age: 15.2 ± 1.1; M follow‐up age: 17.7 ± 1.2; 34 females) completed a second scan at 2‐ or 3‐year follow‐up. Voxel‐based morphometry assessed global and regional gray matter (GM) and white matter (WM) volumes. Body fat percentage was assessed yearly over follow‐up.

Results

Baseline global/regional GM/WM volume did not predict body fat gain over follow‐up. Adolescents who gained body fat showed greater decreases in GM volume in the putamen compared with those who showed loss of body fat. Adolescents who gained body fat showed greater increases in WM volume in the anterior cingulate cortex compared with those who showed stability of or loss of body fat.

Conclusions

Body fat gain versus stability and loss produce GM and WM volume changes, rather than baseline volumetric differences predicting body fat gain.
Weight loss and carotid intima‐media thickness—a meta‐analysis
Authors: Skilton Michael R. , Yeo Si Qin , Ne Jia Yi Anna , Celermajer David S. , Caterson Ian D. , Lee Crystal Man Ying
Published: December 2016

Objective

Obesity is a risk factor for clinical cardiovascular disease, putatively via increased burden of atherosclerosis. It remains contentious as to whether weight loss in people with obesity is accompanied by a reduction in intima‐media thickness, a noninvasive marker of subclinical atherosclerosis, consistent with a lowering of risk of cardiovascular events.

Methods

A systematic literature search was performed to identify all surgical and nonsurgical weight loss interventions that reported intima‐media thickness. A meta‐analysis was undertaken to obtain pooled estimates for change in intima‐media thickness.

Results

From the 3,197 articles screened, 9 studies were included in the meta‐analysis, with a total of 393 participants who lost an average of 16 kg (95% CI 9.4–22.5) of body weight over an average follow‐up of 20 months. The pooled mean change in carotid intima‐media thickness was −0.03 mm (95% CI −0.05 to −0.01), which was similar between surgical and nonsurgical interventions.

Conclusions

In people with obesity, weight loss was associated with a reduction in carotid intima‐media thickness, consistent with a lowering in risk of cardiovascular events.
Loss of dual‐specificity phosphatase‐2 promotes angiogenesis and metastasis via up‐regulation of interleukin‐8 in colon cancer
Authors: Lin Shih‐Chieh , Hsiao Kuei‐Yang , Chang Ning , Hou Pei‐Chi , Tsai Shaw‐Jenq
Published: December 2016

Dual‐specificity phosphatase 2 (DUSP2) is a negative regulator of mitogen‐activated protein kinases. Our previous study showed that DUSP2 expression is down‐regulated in many human cancers and loss of DUSP2 promotes cancer progression; however, the underlying mechanism remains largely uncharacterized. Herein, we found that loss of DUSP2 induces angiogenesis, while forced expression of DUSP2 inhibits microvessel formation in xenografted mouse tumours. Genome‐wide screening of expression profiles, and meta‐analysis of clinical data, identified that the level of interleukin‐8 (IL‐8) correlated negatively with that of DUSP2, suggesting that it may be a downstream target of DUSP2. Molecular characterization revealed that DUSP2 inversely regulates IL‐8 expression, mediated by ERK1/2 and C/EBPα‐dependent transcriptional regulation. Further study showed that hypoxia‐induced IL‐8 expression in cancer cells is also mediated via down‐regulation of DUSP2. Treatment with the IL‐8 receptor inhibitor reparixin or knockdown of IL‐8 in cancer cells abolished angiogenesis induced by loss of DUSP2. Functionally, knockdown of DUSP2 enhanced tumour growth and metastasis, which were abolished by treatment with reparixin or knockdown of IL‐8 in an orthotopic mouse model. Taken together, our results demonstrate that hypoxia inhibits DUSP2 expression in colon cancer, leading to up‐regulation of IL‐8, which facilitates angiogenesis and tumour metastasis. Our findings suggest that blocking hypoxia–DUSP2–IL‐8 signalling may be a plausible approach for therapeutic intervention in cancer. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Effects of long‐term ethanol consumption and Aldh1b1 depletion on intestinal tumourigenesis in mice
Authors: Müller Mike F , Zhou Ying , Adams David J , Arends Mark J
Published: December 2016

Ethanol and its metabolite acetaldehyde have been classified as carcinogens for the upper aerodigestive tract, liver, breast, and colorectum. Whereas mechanisms related to oxidative stress and Cyp2e1 induction seem to prevail in the liver, and acetaldehyde has been proposed to play a crucial role in the upper aerodigestive tract, pathological mechanisms in the colorectum have not yet been clarified. Moreover, all evidence for a pro‐carcinogenic role of ethanol in colorectal cancer is derived from correlations observed in epidemiological studies or from rodent studies with additional carcinogen application or tumour suppressor gene inactivation. In the current study, wild‐type mice and mice with depletion of aldehyde dehydrogenase 1b1 (Aldh1b1), an enzyme which has been proposed to play an important role in acetaldehyde detoxification in the intestines, received ethanol in drinking water for 1 year. Long‐term ethanol consumption led to intestinal tumour development in wild‐type and Aldh1b1‐depleted mice, but no intestinal tumours were observed in water‐treated controls. Moreover, a significant increase in DNA damage was detected in the large intestinal epithelium of ethanol‐treated mice of both genotypes compared with the respective water‐treated groups, along with increased proliferation of the small and large intestinal epithelium. Aldh1b1 depletion led to increased plasma acetaldehyde levels in ethanol‐treated mice, to a significant aggravation of ethanol‐induced intestinal hyperproliferation, and to more advanced features of intestinal tumours, but it did not affect intestinal tumour incidence. These data indicate that ethanol consumption can initiate intestinal tumourigenesis without any additional carcinogen treatment or tumour suppressor gene inactivation, and we provide evidence for a role of Aldh1b1 in protection of the intestines from ethanol‐induced damage, as well as for both carcinogenic and tumour‐promoting functions of acetaldehyde, including increased progression of ethanol‐induced tumours. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Care‐related predictors for negative intrusive thoughts after prostate cancer diagnosis—data from the prospective LAPPRO trial
Authors: Thorsteinsdottir Thordis , Valdimarsdottir Heiddis , Hauksdottir Arna , Stranne Johan , Wilderäng Ulrica , Haglind Eva , Steineck Gunnar
Published: December 2016

Objective

Negative intrusive thoughts about one's prostate cancer have been associated with depressive mood and impaired quality of life among prostate cancer patients. However, little is known about possible predictors for negative intrusive thoughts among this group. We aimed to identify health‐ and care‐related predictors for such thoughts among a population of men newly diagnosed with prostate cancer and undergoing radical prostatectomy.

Methods

In the LAPPRO‐trial, 3154 men (80%) answered study‐specific questionnaires at admission and 3 months after surgery. Questions concerned socio‐demographics, health, uncertainty, preparedness for symptoms, and the outcome—negative intrusive thoughts. Associations between variables were analyzed by log‐binominal and multivariable approach.

Results

The strongest predictor of negative intrusive thoughts at admission to surgery was uncertainty of cure, followed by binge drinking, poor physical health, antidepressant medication, not being prepared for urinary symptoms, age under 55, and physical pain. Reporting it not probable to obtain urinary symptoms after surgery lowered the odds. Negative intrusive thoughts before surgery were the strongest predictor for such thoughts 3 months later followed by uncertainty of cure, physical pain, younger age, living alone, and poor self‐reported physical health.

Conclusions

Our findings showed an association of preoperative uncertainty of cure as well as low preparedness for well‐known surgery‐induced symptoms with higher occurrence of negative intrusive thoughts about prostate cancer. Future studies should examine if interventions designed to have healthcare professionals inform patients about their upcoming prostatectomy reduce patients' negative intrusive thoughts and thereby, improve their psychological well‐being.
A combined low‐pressure hydrogen peroxide evaporation plus hydrogen plasma treatment method for sterilization − Part 2: An intercomparison study of different biological systems
Authors: Lackmann Jan‐Wilm , Fiebrandt Marcel , Raguse Marina , Kartaschew Konstantin , Havenith Martina , Bandow Julia E. , Moeller Ralf , Awakowicz Peter , Stapelmann Katharina
Published: December 2016

Low‐pressure plasmas are a promising alternative to modern sterilization processes. As plasma is a surface process, multilayered stacks of spores are a crucial challenge to overcome. Here, a combined process of condensed hydrogen peroxide and hydrogen plasma is analyzed for its efficacy against various spore concentrations showing a clear increase in efficacy using a combined process compared to the two steps used separately. Besides spores, protein contaminations are a major issue in clinics and the combined process is investigated for protein removal efficiency using the well‐established BSA model. Furthermore, RNase A serves as a difficult‐to‐inactivate protein model to investigate protein inactivation efficiency. Finally, inactivation mechanisms of RNase A with a special focus on sulfur‐based modifications are investigated using Raman spectroscopy.
Holey Graphitic Carbon Derived from Covalent Organic Polymers Impregnated with Nonprecious Metals for CO2 Capture from Natural Gas
Authors: Xie Chengpeng , Huo Feng , Huang Yan , Cheng Yuanhui , Liu Guangqing , Xiang Zhonghua
Published: December 2016

Natural gas (NG), as a renewable and clean energy gas, is considered to be one of the most attractive energy carriers owing to its high calorific value, low price, and less pollution. Efficiently capturing CO2 from NG is a very important issue since CO2 reduces energy density of natural gas and corrodes equipment in the presence of water. In this study, the authors use holey graphene‐like carbon derived from covalent organic polymers (COP) impregnated with nonprecious metals, i.e., COP graphene, as highly efficient separation materials. The dual‐site Langmuir–Freundlich adsorption model based ideal absorbed solution theory is applied to explore the adsorption selectivity. The experimental results along with first principles calculations show Mn‐impregnated COP graphene exhibits greater CO2/CH4 selectivity than Fe and Co impregnated materials. Particularly, the selectivity of C–COP–P–Mn reaches 11.4 at 298 K and 12 bars, which are much higher than those in many reported conventional porous materials and can be compared to the highest separation performance under similar condition. Importantly, all the three COP graphene show remarkably high regenerability (R > 77%), which are much better than many reported promising zeolites, active carbon, and metal organic frameworks. Accordingly, COP graphene are promising cyclic adsorbents with high selectivity for separation and purification of CO2 from natural gas.
Information work in information science research and practice
Authors: Huvila Isto , Lloyd Annemaree , Budd John M. , Palmer Carole , Toms Elaine
Published: December 2016

Information science and technology researchers and practitioners discuss information activities a broad range of terms. A concept that often appears in colloquial discussions of information activities but that has received less systematic attention is that of information work. This panel gathers a group of information science researchers who have explicitly used the notion of information work in their research to discuss how the concept can inform information science and technology research, and practice.