bluuebunny/crossref_metadata_2025 huggingface dataset:
The adaptation of waste-to-energy technologies: towards the conversion of municipal solid waste into a renewable energy resource
Authors: Bishoge Obadia Kyetuza , Huang Xinmei , Zhang Lingling , Ma Hongzhi , Danyo Charity
Published: February 2019

Currently, there are an estimated 1.3 billion tonnes of municipal solid waste (MSW) generated per year globally, and this quantity is predicted to increase to 2.2 billion tonnes annually by 2025. If not well treated, this rapid growth of waste products can lead to socio-economic and environmental problems. Waste is potentially a misplaced valuable resource that can be converted and utilized in different ways such as renewable energy resources for the realization of sustainable development. Presently, waste-to-energy technologies (WtETs) are considered to be an encouraging advanced technology that is applied to convert MSW into a renewable energy resource (methane, biogas, biofuels or biodiesel, ethanol, syngas, or alcohol). WtETs can be biochemical (fermentation, anaerobic digestion, landfill with gas capture, and microbial fuel cell), thermochemical (incineration, thermal gasification, and pyrolysis), or chemical (esterification). This review mainly aims to provide an overview of the applications of these technologies by focusing on anaerobic digestion as biological (nonthermal) treatment technologies, and incineration, pyrolysis, and gasification processes as thermal treatment processes. Landfill gas utilization technologies, biological hydrogen production processes, and microbial fuel cells also are assessed. In addition, the contemporary risks and challenges of WtETs are reviewed.
How do community-level climate change vulnerability assessments treat future vulnerability and integrate diverse datasets? A review of the literature
Authors: Windfeld Emma J. , Ford James D. , Berrang-Ford Lea , McDowell Graham
Published: February 2019

Community-level vulnerability assessments (VAs) are important for understanding how populations experience vulnerabilities to climate change in different ways given local socioeconomic and environmental factors. Despite recent expansion in the literature that evaluates vulnerability at the local level, approaches to understanding future scenarios and to integrating climatic and nonclimatic factors are inconsistent and often lack clear methodological information. This study utilized systematic review methods to characterize and compare future scenarios and the integration of climatic and nonclimatic stimuli in community-focused VAs published over the last five years. Five common methods for assessing future dimensions of vulnerability were characterized. Key challenges regarding sources and scales of information were highlighted alongside methods to integrate data spanning climatic and nonclimatic information at scales ranging from local to global. The majority of VAs considered current and past vulnerability; few VAs incorporated future scenarios and these studies focused on future climatic conditions while largely overlooking changes in nonclimatic drivers of vulnerability. Approaches to evaluate future dimensions of vulnerability included climate model projections, socioeconomic model projections, temporal analogue approaches, longitudinal approaches, and local perceptions. These methods often failed to capture the dynamic interactions between variables through time, as future impacts are unlikely to follow previous patterns of change. To combine datasets of different scales, VAs created vulnerability indices, overlaid spatial datasets, or used expert judgement. These approaches tended to aggregate local characteristics to the regional level at the expense of community specificity. There is a need for methodological advances to assess future scenarios and to combine datasets in the field of community-level climate change VAs to make these studies more responsive to local realities and relevant to the development of climate change adaptation strategies.
Modality-Invariant Image-Text Embedding for Image-Sentence Matching
Authors: Liu Ruoyu , Zhao Yao , Wei Shikui , Zheng Liang , Yang Yi
Published: February 2019

Performing direct matching among different modalities (like image and text) can benefit many tasks in computer vision, multimedia, information retrieval, and information fusion. Most of existing works focus on class-level image-text matching, called
cross-modal retrieval
, which attempts to propose a uniform model for matching images with all types of texts, for example, tags, sentences, and articles (long texts). Although cross-model retrieval alleviates the heterogeneous gap among visual and textual information, it can provide only a rough correspondence between two modalities. In this article, we propose a more precise image-text embedding method, image-sentence matching, which can provide heterogeneous matching in the instance level. The key issue for image-text embedding is how to make the distributions of the two modalities consistent in the embedding space. To address this problem, some previous works on the cross-model retrieval task have attempted to pull close their distributions by employing adversarial learning. However, the effectiveness of adversarial learning on image-sentence matching has not been proved and there is still not an effective method. Inspired by previous works, we propose to learn a modality-invariant image-text embedding for image-sentence matching by involving adversarial learning. On top of the triplet loss--based baseline, we design a modality classification network with an adversarial loss, which classifies an embedding into either the image or text modality. In addition, the multi-stage training procedure is carefully designed so that the proposed network not only imposes the image-text similarity constraints by ground-truth labels, but also enforces the image and text embedding distributions to be similar by adversarial learning. Experiments on two public datasets (Flickr30k and MSCOCO) demonstrate that our method yields stable accuracy improvement over the baseline model and that our results compare favorably to the state-of-the-art methods.
Electrocatalytic Activity of Galvanostatically Deposited Ni thin Films for Methanol Electrooxidation
Authors: Salinas-Quezada Maria Paula , Crespo-Yapur D. Alfonso , Cano-Marquez Abraham , Videa Marcelo
Published: February 2019

Nickel and nickel-based nanomaterials are an attractive choice to replace noble metals as electrocatalyst in alkaline direct alcohol fuel cells (DAFCs) owing to their lower cost and suitable electrocatalytic activity. Among the different synthetic methods available for the production of nanostructured materials, galvanostatic electrodeposition offers a fast and simple means of fabricating active electrodes. Therefore, thin-layers of nickel were electrodeposited onto polycrystalline gold electrodes using constant current pulses from an electrolyte containing 50 mM NiSO4. The electrocatalytic properties of the nickel nanostructures in alkaline medium, in which the catalytic species NiOOH is formed, were evaluated through cyclic voltammetry in 0.5 M methanol + 1 M KOH. The effects of current density pulse and the presence of sulfate or chloride anions in the supporting electrolyte on the electrocatalytic activity of the deposits were studied using Ni(OH)2 surface concentration, Gamma, and electrocatalytic intensity, EI, as performance parameters. It was found that highest electrolcatalytic activities were obtained when using current densities pulses close to 4.0 mA/cm2 in the presence of sulfates. It was found that the presence of sulfates leads to a strong correlation between the electrocatalytic activity for the oxidation of methanol and the surface concentration of Ni(OH)2.
The historical context and scientific legacy of John O. Holloszy
Authors: Hagberg James M. , Coyle Edward F. , Baldwin Kenneth M. , Cartee Gregory D. , Fontana Luigi , Joyner Michael J. , Kirwan John P. , Seals Douglas R. , Weiss Edward P.
Published: February 2019

John O. Holloszy, as perhaps the world’s preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy’s outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.
Voluntary wheel running in the late dark phase ameliorates diet-induced obesity in mice without altering insulin action
Authors: Dalbram Emilie , Basse Astrid L. , Zierath Juleen R. , Treebak Jonas T.
Published: February 2019

Metabolic dysfunction and Type 2 diabetes are associated with perturbed circadian rhythms. However, exercise appears to ameliorate circadian disturbances, as it can phase-shift or reset the internal clock system. Evidence is emerging that exercise at a distinct time of day can correct misalignments of the circadian clock and influence energy metabolism. This suggests that timing of exercise training can be important for the prevention and management of metabolic dysfunction. In this study, obese, high-fat diet-fed mice were subjected to voluntary wheel running (VWR) at two different periods of the day to determine the effects of time-of-day-restricted VWR on basal and insulin-stimulated glucose disposal. VWR in the late dark phase reduced body weight gain compared with VWR in the beginning of the dark phase. Conversely, time-of-day-restricted VWR did not influence insulin action and glucose disposal, since skeletal muscle and adipose tissue glucose uptake and insulin signaling remained unaffected. Protein abundance of the core clock proteins, brain-muscle arnt-like 1 (BMAL1), and circadian locomotor output control kaput (CLOCK), were increased in skeletal muscle after VWR, independent of whether mice had access to running wheels in the early or late dark phase. Collectively, we provide evidence that VWR in the late dark phase ameliorates diet-induced obesity without altering insulin action or glucose homeostasis.

NEW & NOTEWORTHY Exercise appears to ameliorate circadian disturbances as it can entrain the internal clock system. We provide evidence that voluntary wheel running increases core clock protein abundance and influences diet-induced obesity in mice in a time-of-day-dependent manner. However, the effect of time-of-day-restricted voluntary wheel running on body weight gain is not associated with enhanced basal- and insulin-stimulated glucose disposal, suggesting that time-of-day-restricted voluntary wheel running affects energy homeostasis rather than glucose homeostasis.
Reduced corticospinal responses in older compared with younger adults during submaximal isometric, shortening, and lengthening contractions
Authors: Škarabot Jakob , Ansdell Paul , Brownstein Callum G. , Hicks Kirsty M. , Howatson Glyn , Goodall Stuart , Durbaba Rade
Published: February 2019

The aim of this study was to assess differences in motor performance, as well as corticospinal and spinal responses to transcranial magnetic and percutaneous nerve stimulation, respectively, during submaximal isometric, shortening, and lengthening contractions between younger and older adults. Fifteen younger [26 yr (SD 4); 7 women, 8 men] and 14 older [64 yr (SD 3); 5 women, 9 men] adults performed isometric and shortening and lengthening dorsiflexion on an isokinetic dynamometer (5°/s) at 25% and 50% of contraction type-specific maximums. Motor evoked potentials (MEPs) and H reflexes were recorded at anatomical zero. Maximal dorsiflexor torque was greater during lengthening compared with shortening and isometric contractions ( P < 0.001) but was not age dependent ( P = 0.158). However, torque variability was greater in older compared with young adults ( P < 0.001). Background electromyographic (EMG) activity was greater in older compared with younger adults ( P < 0.005) and was contraction type dependent ( P < 0.001). As evoked responses are influenced by both the maximal level of excitation and background EMG activity, the responses were additionally normalized {[MEP/maximum M wave (Mmax)]/root-mean-square EMG activity (RMS) and [H reflex (H)/Mmax]/RMS}. (MEP/Mmax)/RMS and (H/Mmax)/RMS were similar across contraction types but were greater in young compared with older adults ( P < 0.001). Peripheral motor conduction times were prolonged in older adults ( P = 0.003), whereas peripheral sensory conduction times and central motor conduction times were not age dependent ( P ≥ 0.356). These data suggest that age-related changes throughout the central nervous system serve to accommodate contraction type-specific motor control. Moreover, a reduction in corticospinal responses and increased torque variability seem to occur without a significant reduction in maximal torque-producing capacity during older age.

NEW & NOTEWORTHY This is the first study to have explored corticospinal and spinal responses with aging during submaximal contractions of different types (isometric, shortening, and lengthening) in lower limb musculature. It is demonstrated that despite preserved maximal torque production capacity corticospinal responses are reduced in older compared with younger adults across contraction types along with increased torque variability during dynamic contractions. This suggests that the age-related corticospinal changes serve to accommodate contraction type-specific motor control.
Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis
Authors: Guo Jinbang , Hardie William D. , Cleveland Zackary I. , Davidson Cynthia , Xu Xuefeng , Madala Satish K. , Woods Jason C.
Published: February 2019

To longitudinally monitor progressive fibrosis in the transforming growth factor-α (TGF-α) transgenic mouse model of lung fibrosis, we used retrospective self-gating ultrashort echo time (UTE) magnetic resonance imaging (MRI) to image mouse lung at baseline and after 4 and 8 wk of fibrosis initiation via doxycycline administration. Only bitransgenic mice were used in this study and divided into two cohorts: six mice were fed doxycycline food to induce lung fibrosis (referred to as Dox cohort), and five other mice were fed normal food (referred to as control cohort). Lung mechanics, histology, and hydroxyproline were assessed after the final MRI. A linear mixed-effects model was used to analyze MRI-derived longitudinal lung-function parameters. Tidal volume decreased at a rate of −0.016 ± 0.002 ml/week [χ2(1) = 16.48, P < 0.001] for Dox cohort and increased at a rate of 0.010 ± 0.003 ml/week [χ2(1) = 6.37, P = 0.01] for control cohort. Minute ventilation decreased at a rate of −1.71 ± 0.26 ml·min-1·wk-1 [χ2(1) = 14.04, P < 0.001] for Dox cohort but did not change significantly over time for control cohort. High-density lung volume percentage increased at a rate of 3.9 ± 0.7%/wk for Dox cohort [χ2(1) = 11.47, P < 0.001] but did not change significantly over time for control cohort. MRI-derived lung structure and function parameters were strongly correlated with pleural thickness, hydroxyproline content, lung compliance, airway resistance, and airway elastance. We conclude that self-gating UTE MRI could be used to longitudinally monitor lung fibrosis in the TGF-α transgenic mouse model.

NEW & NOTEWORTHY Self-gating UTE MRI was used to monitor morphology and physiology in lung fibrosis in a transforming growth factor-α transgenic mouse model. Tidal volume was shown for the first time to correlate strongly with conventional metrics of fibrosis such as hydroxyproline and pleural thickness.
Regional distribution of chest wall displacements in infants during high-frequency ventilation
Authors: Zannin Emanuela , Ventura Maria Luisa , Dognini Giulia , Veneroni Chiara , Pillow Jane J. , Tagliabue Paolo E. , Dellacà Raffaele L.
Published: February 2019

The distribution of ventilation during high-frequency ventilation (HFV) is asynchronous, nonhomogeneous, and frequency dependent. We hypothesized that differences in the regional distribution of ventilation at different oscillatory frequencies may affect gas exchange efficiency. We studied 15 newborn infants with a median gestational age of 28.9 (26.4–30.3) wk and body weight of 1.0 (0.8–1.4) kg. Five ventilation frequencies (5, 8, 10, 12, and 15 Hz) were tested, keeping carbon dioxide diffusion coefficient constant. The displacements of 24 passive markers placed on the infant’s chest wall were measured by optoelectronic plethysmography. We evaluated the amplitude and phase shift of displacements of single markers placed along the midline and the regional displacements of the chest wall surface. Blood gases were unaffected by frequency. Chest wall volume changes decreased from 1.6 (0.4) ml/kg at 5 Hz to 0.7 ml/kg at 15 Hz. At all frequencies, the abdomen (AB) oscillated more markedly than the ribcage (RC). The mean (SD) AB/RC ratio was 1. 95 (0.7) at 5 Hz, increased to 2.1 (1.3) at 10 Hz, and then decreased to 1.1 (0.5) at 15 Hz ( P < 0.05 vs. 10 Hz). Volume changes in the AB lagged the RC and this phase shift increased with frequency. The AB oscillated more than the RC at all frequencies. Regional oscillations were highly inhomogeneous up to 10 Hz, and they became progressively more asynchronous with increasing frequency. When the carbon dioxide diffusion coefficient is held constant, such differences in regional chest wall expansion do not affect gas exchange.

NEW & NOTEWORTHY We characterized the regional distribution of chest wall displacements in infants receiving high-frequency oscillatory ventilation at different frequencies. When carbon dioxide diffusion coefficient is held constant, there is no combination of frequency and tidal volume that optimizes gas exchange. The relative displacement between different chest wall compartments is not affected by frequency. However, at high frequencies, chest wall displacements are lower, with the potential to reduce total and regional overdistension without affecting gas exchange.
Development of an Anchoring System for the Soft Asteroid Landing Exploration
Authors: Zhao Zhijun , Wang Shuang , Li Delun , Wang Hongtao , Wang Yongbing , Zhao Jingdong
Published: February 2019

The landing mechanism is easy to flow away from the surface of the asteroid, as there is nearly no gravity on the asteroid. One of the most problems for the asteroid landing exploration is to anchor the landing mechanism on the asteroid surface. In the paper, an anchoring system employed on the soft asteroid anchoring is designed. It is mainly composed of penetrating unit, advancing unit, winding unit, damping unit, and so on. On the basis of the mechanical design, the resistance characteristic of the anchor body in penetrating process is analyzed, and the shape of the anchor tip is designed with the least resistance as the constraint. Then, the validity of the anchor tip design is tested by comparing penetrating ability of different anchor tips. Finally, the penetrating and the anchoring performances of the anchoring system are tested in a variety of media.
Tension‐Compression Damage Model with Consistent Crack Bandwidths for Concrete Materials
Authors: He Wei , Xu Ying , Cheng Yu , Jia Peng-Fei , Fu Ting-Ting
Published: February 2019

This paper proposes a tension‐compression damage model for concrete materials, formulated within the framework of thermodynamics of irreversible processes. The aim of this work is to solve the following problems: the premature divergence of numerical solutions under general loading conditions due to the conflict of tensile and compressive damage bounding surfaces, which is a result of the application of the spectral decomposition method to distinguish tension and compression, and the unsatisfactory reproduction of distinct tension‐compression behaviors of concrete by strain‐driven damage models. The former is solved by the sign of the volumetric deformation, while the latter is solved via two separated dissipation mechanisms. Moreover, of specific interest is an improved solution to the problem of mesh‐size dependency using consistent crack bandwidths, which takes into account situations with irregular meshes and arbitrary crack directions in the context of the crack band approach. The performance of the model is validated by the well‐documented experimental data. The simplicity and the explicit integration of the constitutive equations render the model well suitable for large‐scale computations.
A Study on Contestable Regions in Europe through the Use of a New Rail Cost Function: An Application to the Hinterland of the New Container Terminal of Leghorn Port
Authors: Lupi Marino , Pratelli Antonio , Canessa Mattia , Lorenzini Andrea , Farina Alessandro
Published: February 2019

In this paper, the potential hinterland of the new container terminal of the port of Leghorn (Livorno in Italian) is studied. The study actually analyses the competitiveness of major European ports with respect to some of the most contestable regions in Europe. Travel time and monetary costs of railway paths, connecting ports to their hinterland, have been determined. The rail network of a large part of Europe was modelled using a graph. To each link, which represents a portion of the rail line, a cost function is associated. The travel time on the link is determined from the average speed, which has been determined from the maximum speed via formulae obtained through linear regression. The few cost functions that exist in current literature for the computation of the cost of a rail link are not detailed enough. Therefore, a new cost function has been developed. All cost components were determined in detail: the staff cost, the amortisation, maintenance, and insurance costs of locomotives and wagons, the cost of the usage of rail track, the traction cost. The traction cost was calculated in detail from all resistances to motion. Moreover, for each rail link, the number of locomotives needed to operate the train and the maximum towable weight were determined. The monetary value of time in freight transport registers a high variability; therefore, three different optimisations of the paths—by travel times, monetary costs, and generalised costs—between each origin–destination pair were carried out. The rates of competitiveness of the ports with respect to the examined European contestable regions were analysed.
Investigation on Microstructure of Potassium Nitrate/Sodium Nitrate Composites for Solar Storage System
Authors: Mao Qianjun , Liu Ning , Peng Li , Wu Hongjun
Published: February 2019

The performance of the material is determined by its structure, i.e., the composition of the material elements of the atomic structure, the molecular structure, and atoms or molecules in space arrangement and the aggregation characteristics. The microstructure of the material has important implications for the material performance. In this paper, five phase change materials, potassium nitrate, sodium nitrate, and the composites of KNO3-NaNO3/graphite (3%, 6%, and 9%), have been studied by the experiment, and the aim is to improve the storage performance of the solar storage system. The results show that potassium nitrate and sodium nitrate are significantly different in microstructure, that is, potassium nitrate is a layered structure and the sodium nitrate is a network structure. And, the graphite as additives can be physically combined with the molten salts, which leads to a different performance and distribution in the mixture. Therefore, it is an effective method in improving the performance of molten salts by using graphite as the supporting material. The results can provide a reference to future choose for solar storage materials.
The Synthesis of 2D CH3NH3PbI3 Perovskite Films with Tunable Bandgaps by Solution Deposition Route
Authors: Loryuenyong Vorrada , Thongpon Pajaree , Saudmalai Sasathorn , Buasri Achanai
Published: February 2019

Nowadays, organo-lead halide is one of the most interesting materials for perovskite solar cells. This is because of its ease of fabrication, long absorption wavelength region, and long diffusion length. In this study, we investigated the bandgap tuning of hybrid mixed-halide perovskite films. The films were prepared by sequential two-step deposition technique, using 5-ammonium valeric acid iodide (5-AVAI), PbI2, and a mixture of CH3NH3I and CH3NH3Br as precursor solutions. The results confirmed the formation of 2D perovskites in the presence of 5-AVAI. The obtained films had higher moisture resistance, better surface coverage, and smaller grain size, compared to the films without 5-AVAI. With the introduction of Br− ions, the change in the lattice parameter was observed. The bandgap was also found to increase with increasing Br− content.
Phase-Only Antenna Array Reconfigurability with Gaussian-Shaped Nulls for 5G Applications
Authors: Buttazzoni Giulia , Comisso Massimiliano , Ruzzier Federico , Vescovo Roberto
Published: February 2019

This paper presents a fast iterative method for the synthesis of linear and planar antenna arrays of arbitrary geometry that provides pattern reconfigurability for 5G applications. The method enables to generate wide null regions shaped according to a Gaussian distribution, which complies with recent measurements on millimeter-wave (mmWave) angular dispersion. A phase-only control approach is adopted by moving from the pattern provided by a uniformly excited array and iteratively modifying the sole phases of the excitations. This allows the simplification of the array feeding network, hence reducing the cost of realization of 5G base stations and mobile terminals. The proposed algorithm, which is based on the method of successive projections, relies on closed-form expressions for both the projectors and the null positions, thus allowing a fast computation of the excitation phases at each iteration. The effectiveness of the proposed solution is checked through numerical examples compliant with 5G mmWave scenarios and involving linear and concentric ring arrays.
Gauge from Holography and Holographic Gravitational Observables
Authors: Zapata José A.
Published: February 2019

In a spacetime divided into two regions U1 and U2 by a hypersurface Σ, a perturbation of the field in U1 is coupled to perturbations in U2 by means of the holographic imprint that it leaves on Σ. The linearized gluing field equation constrains perturbations on the two sides of a dividing hypersurface, and this linear operator may have a nontrivial null space. A nontrivial perturbation of the field leaving a holographic imprint on a dividing hypersurface which does not affect perturbations on the other side should be considered physically irrelevant. This consideration, together with a locality requirement, leads to the notion of gauge equivalence in Lagrangian field theory over confined spacetime domains. Physical observables in a spacetime domain U can be calculated integrating (possibly nonlocal) gauge invariant conserved currents on hypersurfaces such that ∂Σ⊂∂U. The set of observables of this type is sufficient to distinguish gauge inequivalent solutions. The integral of a conserved current on a hypersurface is sensitive only to its homology class [Σ], and if U is homeomorphic to a four ball the homology class is determined by its boundary S=∂Σ. We will see that a result of Anderson and Torre implies that for a class of theories including vacuum general relativity all local observables are holographic in the sense that they can be written as integrals of over the two-dimensional surface S. However, nonholographic observables are needed to distinguish between gauge inequivalent solutions.
Phosphatase 1 Nuclear Targeting Subunit Mediates Recruitment and Function of Poly (ADP-Ribose) Polymerase 1 in DNA Repair
Authors: Wang Feifei , Zhu Songli , Fisher Laura A. , Wang Ling , Eurek Nicholas J. , Wahl James K. , Lan Li , Peng Aimin
Published: February 2019

PARP, particularly PARP1, plays an essential role in the detection and repair of DNA single-strand breaks and double-strand breaks. PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein poly ADP-ribosylation (PARylation). However, the molecular mechanisms underlying the recruitment and activation of PARP1 in DNA repair are not fully understood. Here we show that phosphatase 1 nuclear targeting subunit 1 (PNUTS) is a robust binding partner of PARP1. Inhibition of PNUTS led to strong accumulation of endogenous DNA damage and sensitized the cellular response to a wide range of DNA-damaging agents, implicating PNUTS as an essential and multifaceted regulator of DNA repair. Recruitment of PNUTS to laser-induced DNA damage was similar to that of PARP1, and depletion or inhibition of PARP1 abrogated recruitment of PNUTS to sites of DNA damage. Conversely, PNUTS was required for efficient induction of substrate PARylation after DNA damage. PNUTS bound the BRCA1 C-terminal (BRCT) domain of PARP1 and was required for the recruitment of PARP1 to sites of DNA damage. Finally, depletion of PNUTS rendered cancer cells hypersensitive to PARP inhibition. Taken together, our study characterizes PNUTS as an essential partner of PARP1 in DNA repair and a potential drug target in cancer therapy.

Significance:

These findings reveal PNUTS as an essential functional partner of PARP1 in DNA repair and suggest its inhibition as a potential therapeutic strategy in conjunction with DNA-damaging agents or PARP inhibitors.

See related commentary by Murai and Pommier, p. 2460
A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer
Authors: Lévesque Eric , Caron Patrick , Lacombe Louis , Turcotte Véronique , Simonyan David , Fradet Yves , Aprikian Armen , Saad Fred , Carmel Michel , Chevalier Simone , Guillemette Chantal
Published: February 2019

Background:

In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression.

Methods:

The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.

Results:

The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054).

Conclusions:

In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.

Impact:

The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.
Optimal Cutoff Scores for Dementia and Mild Cognitive Impairment in the Brazilian Version of the Montreal Cognitive Assessment among the Elderly
Authors: Pinto Tiago C.C. , Santos Marília S.P. , Machado Leonardo , Bulgacov Tatiana M. , Rodrigues-Junior Antônio L. , Silva Gabriela A. , Costa Maria Lúcia G. , Ximenes Rosana C.C. , Sougey Everton B.
Published: February 2019

Objective: To propose cutoff scores for the Brazilian version of the Montreal Cognitive Assessment (MoCA-BR) stratified by education in order to detect mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD) in the elderly. Method: A transversal study in health centers was performed on 159 elderly people with 4–12 years of education and 70 of their peers with over 12 years of schooling. The MoCA-BR cutoff scores for screening cognitive impairment were determined based on an ROC curve analysis. Results: The ROC curve analysis indicated that cutoff scores under 20 were good for screening elderly people with cognitive impairment with more than 12 years of education, and scores under 21 were good for screening those with 4–12 years of education. Conclusions: MoCA-BR scores under 21 points (after adding 1 point to the elderly with ≤12 years of education) indicate a need to continue the diagnostic investigation with regular follow-ups.
Ginsenoside-Rg5 Inhibits Retinoblastoma Proliferation and Induces Apoptosis through Suppressing BCL2 Expression
Authors: Cui Yong , Su Yan , Deng Liya , Wang Wenjing
Published: February 2019

Background/Aims: Although the cure rate for retinoblastoma is high, surviving patients are at risk for developing secondary cancers and require life-long follow-up. It is imperative to discover and develop novel therapeutic agents with better efficiency and fewer adverse effects. Ginsenoside-Rg5 is an active derivate from ginseng and exerts anti-cancer activity in breast cancer cells. However, it is still unclear whether ginsenoside-Rg5 has similar anti-cancer functions in retinoblastoma. Methods: Retinoblastoma cells were treated with ginsenoside-Rg5, followed by MTT assay analysis of the cell viability, cell number assay and colony formation assay analyses of cell proliferation, and flow cytometric analysis of apoptosis. Gene mRNA levels and protein levels were determined by quantitative real-time PCR and Western blot, respectively. Results: Ginsenoside-Rg5 inhibited retinoblastoma cell viability in a dose-dependent and time-dependent manner via preventing cell proliferation and inducing cell apoptosis. BCL2 expression was downregulated by ginsenoside-Rg5 treatment via inactivating the AKT signaling pathway. BCL2 overexpression completely eliminated the inhibitory effect of ginsenoside-Rg5 on cancer cell viability. Conclusion: Ginsenoside-Rg5 inhibits cell proliferation and induces apoptosis in retinoblastoma cells by inactivating the AKT signaling pathway, thereby downregulating BCL2 expression.
Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks
Authors: Fielding David , Dalley Andrew J. , Bashirzadeh Farzad , Singh Mahendra , Nandakumar Lakshmy , McCart Reed Amy E. , Black Debra , Kazakoff Stephen , Pearson John V. , Nones Katia , Waddell Nicola , Lakhani Sunil R. , Simpson Peter T.
Published: February 2019

Background: Next-generation sequencing (NGS) in lung cancer specimens from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is usually performed on formalin-fixed paraffin-embedded cell block material. Objectives: Since DNA can be damaged by this process, we investigated the potential of using DNA extracted from Diff-Quik cytology smears made for rapid on-site evaluation during EBUS-TBNA. Methods: In a prospective study, 67 patients undergoing diagnostic EBUS-TBNA were ana­lysed. We compared cell blocks and smears for DNA yields and sequencing (TruSeq Amplicon Cancer Panel) outcomes. Smears were also evaluated for tumour cell fraction and overall cellularity (cell count). Results: Primary lung cancer was diagnosed in 64 patients and metastatic malignancy in 3 patients. The DNA yield from smears was significantly higher than that obtained from matched cell blocks (mean 1,740 vs. 434 ng; p = 0.001). For 33 cases with matched smears and cell blocks the mutation profiles were similar. Smears with abundant malignant cells (using a cut-off of > 25% tumour cell fraction and > 1,000 cells) accurately predicted high (> 50 ng) DNA yield and therefore success in triaging samples to sequencing. In terms of tissue workflow, using only smears as source DNA for sequencing was an improvement in the use of only cell blocks (54/67 [80.6%] vs. 41/67 [61.2%]); however, the use of cell blocks when smears were not available or did not yield sufficient DNA further improved the success rate to 62/67 (92.5%) cases. Conclusion: We recommend smears in laboratory workflows as the primary source of DNA for NGS following an EBUS procedure.
A Multicenter Lung Ultrasound Study on Transient Tachypnea of the Neonate
Authors: Raimondi Francesco , Yousef Nadya , Rodriguez Fanjul Javier , De Luca Daniele , Corsini Iuri , Shankar-Aguilera Shivani , Dani Carlo , Di Guardo Vito , Lama Silvia , Mosca Fabio , Migliaro Fiorella , Sodano Angela , Vallone Gianfranco , Capasso Letizia
Published: February 2019

Background and Aim: Discordant results that demand clarification have been published on diagnostic lung ultrasound (LUS) signs of transient tachypnea of the neonate (TTN) in previous cross-sectional, single-center studies. This work was conducted to correlate clinical and imaging data in a longitudinal and multicenter fashion. Methods: Neonates with a gestational age of 34–40 weeks and presenting with TTN underwent a first LUS scan at 60–180 min of life. LUS scans were repeated every 6–12 h if signs of respiratory distress persisted. Images were qualitatively described and a LUS aeration score was calculated. Clinical data were collected during respiratory distress. Results: We enrolled 65 TTN patients. Thirty-one (47.6%) had a sharp echogenicity increase in the lower lung fields (the “double lung point” or DLP sign). On admission, there was no significant difference between patients with and without DLP in Silverman scores (4 ± 1.5 vs. 4 ± 2.1; p = 0.9) or LUS scores (7.6 ± 2.6 vs. 5.6 ± 3.8; p = 0.12); PaO2/FiO2 (249 ± 93 vs. 252 ± 125; p = 0.91). All initial LUS scans (performed at the onset of distress) and 99.5% of all scans showed a regular pleural line with no consolidation, with only 1 neonate showing consolidation in the follow-up scans. The Silverman and LUS scores were significantly correlated (rho = 0.27; p = 0.02). Conclusion: A regular pleural line with no consolidation is a consistent finding in TTN. The presence of a DLP is not essential for the LUS diagnosis of TTN. A semi-quantitative LUS score correlates well with the clinical course and could be useful in monitoring changes in lung aeration during TTN.
How the Post-Fracture Rehabilitation Choice Affects Brain Function in Older People?
Authors: Mitsuboshi Noriko , Kouzuki Minoru , Mochida Shigeru , Morimoto Kanehito , Urakami Katsuya
Published: February 2019

Background: We investigated how the type of rehabilitation affects brain function and antioxidant potential. Methods: Twenty-eight patients hospitalized for fall-related fractures were assigned to either a physical therapy group or an occupational therapy group. Cognition was assessed using the Touch Panel-type Dementia Assessment Scale (TDAS) and oxidative stress with serum pentosidine levels. Spectral analysis and coherence analysis were also performed. Results: Changes in TDAS scores and serum pentosidine levels did not differ significantly between the 2 therapies. Power spectral analysis revealed a significant intergroup difference in δ waves. Coherence analysis showed significant intergroup differences in the activities of δ waves and β waves. Conclusions: Cognitive function and antioxidant potential did not differ between the 2 types of rehabilitation. However, the impact on cerebral neuronal activity may have differed.
Diabetes Mellitus and Age are Risk Factors of Interval Colon Cancer: A Case-Control Study
Authors: Laish Ido , Mizrahi Joseph , Naftali Timna , Konikoff Fred M.
Published: February 2019

Background and Aims: Interval colorectal cancer (CRC) is largely related to a poor endoscopic performance or different biology in the development of the polyp. However, patient-related factors were less investigated for their association with interval cancer. We thus evaluated tumor and patient characteristics as predictors of interval cancer in a population from Israel. Methods: In this retrospective study, patients that were diagnosed with colon cancer in our institution and had 2 colonoscopies were included. Demographic parameters and tumor characteristics were compared between 84 cases with interval cancer, occurring 1–10 years after a negative colonoscopy, and 983 patients with primary CRC. In addition, patient-related features, including diabetes and diverticulosis, were compared between 51 patients with interval cancer after negative colonoscopy and 255 controls with no cancer and a previous negative colonoscopy. Results: Compared to “positive” controls with primary cancer, patients with interval cancer were older (age 71.3 vs. 67.6, p = 0.003), had proximal tumor location (57 vs. 34%, p < 0.001) and non-advanced (0–2) tumor staging (78.5 vs. 64.8%, p = 0.014). Compared with ­“negative” healthy controls, cases with interval cancer had only higher prevalence of diabetes (31 vs. 15%, p = 0.002). No significant differences were seen between patients with interval cancer occurring < 3 years and after 3–10 years. Conclusions: Patients with Interval cancer tend to be older and have diabetes. These patient groups should be more carefully or more frequently screened for pre-malignant lesions.
Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest
Authors: Usugi Eri , Ishii Kenichiro , Hirokawa Yoshifumi , Kanayama Kazuki , Matsuda Chise , Uchida Katsunori , Shiraishi Taizo , Watanabe Masatoshi
Published: February 2019

Background: Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro. Method: Human skin fibroblasts ASF-4-1 cells and human prostate stromal cells (PrSC) were used as fibroblasts. PANC-1, MIA PaCa-2, and BxPC-3 cells were used as human PCCs. Cell cycle and apoptosis were analyzed using flow cytometer. Results: First, we confirmed that PFD suppressed cell proliferation of ASF-4-1 cells and PrSC and induced G0/G1 cell cycle arrest. Under these experimental conditions, PFD also suppressed cell proliferation and induced G0/G1 cell cycle arrest in all PCCs. In PFD-treated PCCs, expression of p21 was increased but that of CDK2 was not clearly decreased. Of note, PFD did not induce significant apoptosis among PCCs. Conclusions: These results demonstrated that the antifibrotic agent PFD might have antiproliferative effects on PCCs by inducing G0/G1 cell cycle arrest. This suggests that PFD may target not only fibroblasts but also PCCs in the tumor microenvironment of pancreatic cancer.
Intra-Arterial Thrombolysis Improves the Prognosis of Acute Ischemic Stroke Patients without Large Vessel Occlusion
Authors: Shang Shuyi , Zhao Wenbo , Li Chuanhui , Dong Kai , Song Haiqing , Meng Ran , Ren Changhong , Duan Jiangang , Ji Xunming
Published: February 2019

Background and Purpose: Intravenous thrombolysis is known as the only effective reperfusion therapy for acute ischemic stroke (AIS) caused by small branches occlusion. However, it is still unclear whether intra-arterial thrombolysis (IAT) is safe and effective for patients without detectable arterial occlusion. This study evaluated the safety and efficacy of IAT in these patients. Methods: Data were collected on consecutive patients from December 2012 to February 2017 at the Xuanwu Hospital, Capital Medical University. AIS patients without large artery occlusion during digital subtraction angiography (DSA) were divided into 2 groups: (1) Intra-arterial urokinase thrombolysis group (UK group): received intra-arterial urokinase thrombolysis treatment; (2) Control group: cerebral angiography examination only. The primary outcome was 3-month favorable functional outcome (modified Rankin Scale 0–2). Results: A total of 48 patients received urokinase thrombolysis, and 34 patients underwent DSA examination only. The UK group had more frequent favorable functional outcomes (70.8 vs. 50%, p = 0.032) at 3-month follow-up and higher score of National Institutes of Health Stroke Scale improvement on the second day (p = 0.007). One patient (2%) had symptomatic intracerebral hemorrhage and 3 patients (6.3%) had asymptomatic intracerebral hemorrhage (asICH) in the UK group. One patient (3.3%) had asICH in the control group. There were no significant differences about ICH. Conclusions: AIS caused by small branches occlusion could benefit from intra-arterial urokinase thrombolysis, and the risk of intracerebral hemorrhage was not significantly higher.
Association between Sleep Disturbances and Daytime Somnolence in Parkinson’s Disease
Authors: Phattanarudee Siripan , Sangthong Sunisa , Bhidayasiri Roongroj
Published: February 2019

Background: Sleep disturbance is a common problem among patients with Parkinson’s disease (PD). Objectives: To investigate the prevalence of daytime somnolence and night-time sleep disturbances; to characterise the night-time sleep disturbance in patients with daytime somnolence; and to determine the correlation between daytime somnolence and night-time sleep disturbances. Methods: One hundred and sixty patients with PD were included in the study. Each patient completed the Thai version of the Epworth Sleepiness Scale (ESS) questionnaire to evaluate excessive daytime sleepiness (EDS), and the PD Sleep Scale version-2 (PDSS-2) questionnaire to evaluate night-time sleep disturbance. Subjective sleep information and details about the presence or absence of sleep attack (SA) were also obtained from the patients. Results: The types of daytime somnolence found in this study were EDS, SA, and combination of EDS and SA (EDS + SA) with the prevalence rates of 22.5, 3.1 and 6.3%, respectively. The prevalence of night-time sleep disturbance was 46.9%. The most common nocturnal disturbance (82.5%) was “get up at night to pass urine”. There was a significant positive correlation between the ESS score and PDSS-2 total score with a correlation coefficient of 0.16 (p = 0.043). Patients with “EDS + SA” were the most affected by nocturnal disturbances, as they represented the largest group among those patients with night-time disturbances and had the highest PDSS-2 total score (p < 0.05). Conclusion: There are differences in nocturnal sleep disturbances among PD patients with different types of daytime somnolence. The significant positive correlation between the ESS and the PDSS-2 total scores suggests that night-time sleep disturbance may influence daytime somnolence.