bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial
Authors: Crockett Seth D , Barry Elizabeth L , Mott Leila A , Ahnen Dennis J , Robertson Douglas J , Anderson Joseph C , Wallace Kristen , Burke Carol A , Bresalier Robert S , Figueiredo Jane C , Snover Dale C , Baron John A
Published: March 2018

Objective

Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically.

Design

Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D3, both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models.

Results

SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively).

Conclusion

In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6–10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation.

Trial registration number

NCT00153816; Results.
Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome
Authors: McCarthy John M , McCann-Crosby Bonnie M , Rech Megan E , Yin Jiani , Chen Chun-An , Ali May A , Nguyen HaiThuy N , Miller Jennifer L , Schaaf Christian P
Published: March 2018

Background

Nonsense and frameshift mutations in the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13, have been reported to cause Schaaf-Yang syndrome (SYS), a genetic disorder that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties and autism spectrum disorder. Prader-Willi syndrome (PWS) is a genetic disorder characterised by severe infantile hypotonia, hypogonadotrophic hypogonadism, early childhood onset obesity/hyperphagia, developmental delay/intellectual disability and short stature. Scoliosis and growth hormone insufficiency are also prevalent in PWS.

There is extensive documentation of the endocrine and metabolic phenotypes for PWS, but not for SYS. This study served to investigate the hormonal, metabolic and body composition phenotype of SYS and its potential overlap with PWS.

Methods

In nine individuals with SYS (5 female/4 male; aged 5–17 years), we measured serum ghrelin, glucose, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3, follicle-stimulating hormone, luteinising hormone, thyroid-stimulating hormone, free T4, uric acid and testosterone, and performed a comprehensive lipid panel. Patients also underwent X-ray and dual-energy X-ray absorptiometry analyses to assess for scoliosis and bone mineral density.

Results

Low IGF-1 levels despite normal weight/adequate nutrition were observed in six patients, suggesting growth hormone deficiency similar to PWS. Fasting ghrelin levels were elevated, as seen in individuals with PWS. X-rays revealed scoliosis >10° in three patients, and abnormal bone mineral density in six patients, indicated by Z-scores of below −2 SDs.

Conclusion

This is the first analysis of the hormonal, metabolic and body composition phenotype of SYS. Our findings suggest that there is marked, but not complete overlap between PWS and SYS.
Dominant ELOVL1 mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features
Authors: Kutkowska-Kaźmierczak Anna , Rydzanicz Małgorzata , Chlebowski Aleksander , Kłosowska-Kosicka Kamila , Mika Adriana , Gruchota Jakub , Jurkiewicz Elżbieta , Kowalewski Cezary , Pollak Agnieszka , Stradomska Teresa Joanna , Kmieć Tomasz , Jakubowski Rafał , Gasperowicz Piotr , Walczak Anna , Śladowski Dariusz , Jankowska-Steifer Ewa , Korniszewski Lech , Kosińska Joanna , Obersztyn Ewa , Nowak Wieslaw , Śledziński Tomasz , Dziembowski Andrzej , Płoski Rafał
Published: March 2018

Background

Ichthyosis and neurological involvement occur in relatively few known Mendelian disorders caused by mutations in genes relevant both for epidermis and neural function.

Objectives

To identify the cause of a similar phenotype of ichthyotic keratoderma, spasticity, mild hypomyelination (on MRI) and dysmorphic features (IKSHD) observed in two unrelated paediatric probands without family history of disease.

Methods

Whole exome sequencing was performed in both patients. The functional effect of prioritised variant in ELOVL1 (very-long-chain fatty acids (VLCFAs) elongase) was analysed by VLCFA profiling by gas chromatography–mass spectrometry in stably transfected HEK2932 cells and in cultured patient’s fibroblasts.

Results

Probands shared novel heterozygous ELOVL1 p.Ser165Phe mutation (de novo in one family, while in the other family, father could not be tested). In transfected cells p.Ser165Phe: (1) reduced levels of FAs C24:0-C28:0 and C26:1 with the most pronounced effect for C26:0 (P=7.8×10−6 vs HEK293 cells with wild type (wt) construct, no difference vs naïve HEK293) and (2) increased levels of C20:0 and C22:0 (P=6.3×10−7, P=1.2×10−5, for C20:0 and C22:0, respectively, comparison vs HEK293 cells with wt construct; P=2.2×10−7, P=1.9×10−4, respectively, comparison vs naïve HEK293). In skin fibroblasts, there was decrease of C26:1 (P=0.014), C28:0 (P=0.001) and increase of C20:0 (P=0.033) in the patient versus controls. There was a strong correlation (r=0.92, P=0.008) between the FAs profile of patient’s fibroblasts and that of p.Ser165Phe transfected HEK293 cells. Serum levels of C20:0–C26:0 FAs were normal, but the C24:0/C22:0 ratio was decreased.

Conclusion

The ELOVL1 p.Ser165Phe mutation is a likely cause of IKSHD.
Unique clinical characteristics, autoantibodies and medication use in Native American patients with systemic lupus erythematosus
Authors: Kheir Joseph M , Guthridge Carla J , Johnston Jonathon R , Adams Lucas J , Rasmussen Astrid , Gross Timothy F , Munroe Melissa E , Bourn Rebecka L , Sivils Kathy L , Guthridge Joel M , Weisman Michael H , Wallace Daniel J , Anaya Juan-Manuel , Rojas Villarraga Adriana , Jarvis James N , Harley John B , James Judith A
Published: March 2018

Objective

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with varied morbidity and mortality. We assessed clinical presentations, autoantibody specificities and therapeutic interventions in Native American (NA) patients with SLE.

Methods

Patients with SLE meeting 1997 American College of Rheumatology classification criteria (n=3148) were enrolled between 1992 and 2010 in the multiethnic, cross-sectional Lupus Family Registry and Repository. Clinical, demographic and therapeutic information were extracted from medical records using a standardised form and formalised training. Autoantibodies were assessed by indirect immunofluorescence (antinuclear antibodies (ANA) and antidouble-stranded DNA), precipitin (ENA) and ELISA (IgG and IgM anticardiolipins).

Results

NA patients met SLE classification at a younger age (29.89±12.3 years) than European Americans (EA; 32.02±12.87, P=0.0157) and a similar age to African-Americans (AAs) and Hispanics (HIS). More NA patients had concurrent rheumatic diseases or symptoms, such as Raynaud’s phenomenon, interstitial lung disease, Sjӧgren’s syndrome and systemic sclerosis. Compared with EAs, NAs were more likely to have high-titre ANA (≥1:3240; P<0.0001) and had more SLE-associated autoantibodies. Autoantibodies with unknown specificities were more common in NAs (41%) compared with other racial/ethnic groups in this collection (AA: 24%, P=0.0006; EA: 17%, P<0.0001; HIS: 23%, P=0.0050). Fewer NA patients used hydroxychloroquine (68%) compared with others (AA: 74%, P=0.0308; EA: 79%, P=0.0001, HIS: 77%, P=0.0173); this was influenced by lower hydroxychloroquine use in NA patients from Latin America (32%). NA patients had higher rates of methotrexate use (28%) compared with AA (18%, P=0.0006) and HIS patients (14%, P=0.0003), higher azathioprine use (38%) compared with EA patients (30%, P=0.0105) and higher mycophenolate mofetil use (26%) compared with EA (17%, P=0.0012) and HIS patients (11%, P<0.0001).

Conclusions

NA patients are diagnosed with SLE earlier in life and present worse concurrent rheumatic disease symptoms than EA patients. NA patients also are more likely to have expanded autoantibody profiles and precipitins of unknown specificities.
Cerebral organoids: ethical issues and consciousness assessment
Authors: Lavazza Andrea , Massimini Marcello
Published: March 2018

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids (ie, human embryos) and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or (which is more likely) will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available (the Perturbational Complexity Index, a metric that is directly inspired by the main postulate of the Integrated Information Theory of consciousness), which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary.
Biogeochemistry of U, Ni, and As in two meromictic pit lakes at the Cluff Lake uranium mine, northern Saskatchewan
Authors: von Gunten Konstantin , Warchola Tyler , Donner Mark W. , Cossio Manuel , Hao Weiduo , Boothman Christopher , Lloyd Jonathan , Siddique Tariq , Partin Camille A. , Flynn Shannon L. , Rosaasen Arden , Konhauser Kurt O. , Alessi Daniel S.
Published: March 2018

Open pits, which remain after uranium (U) mining operations cease, can form meromictic lakes that develop suitable conditions for the containment of dissolved and colloidal metals. In this study, the distribution and speciation of U, nickel (Ni), and arsenic (As) in the water column of two meromictic pit lakes was investigated at the decommissioned Cluff Lake mine in northern Saskatchewan. The 28 m deep and older D pit had a chemocline at a 13 m depth, below which it turned anoxic and its meromixis was controlled by iron (Fe) cycling. Below the chemocline both Fe(III) and As(V) were reduced to Fe(II) and As(III), respectively. Iron cycling had a large effect on U distribution because reducing conditions prevented sulfide oxidation and a drop in pH in deeper layers. Metal-reducing bacteria were found to be present at, and below, the chemocline. In the deeper (90 m), larger and more recently flooded DJX pit, two chemoclines were observed at depths of 15 and 65 m. Both were linked to sharp U and Ni concentration gradients. Unlike the D pit, a transition to reducing conditions was not observed in the DJX pit’s water column. However, colloidal U, primarily associated with aluminum oxyhydroxides, was found below the first chemocline. Overall, the meromixis type determined the distribution and speciation of metals and bacteria in the investigated pit lakes, thus providing insights into the use of pit lakes as a potential bioremediation strategy.
Environmental, anthropogenic, and dietary influences on fine-scale movement patterns of Atlantic salmon through challenging waters
Authors: Harbicht Andrew B. , Castro-Santos Theodore , Gorsky Dimitry , Hand David M. , Fraser Dylan J. , Ardren William R.
Published: March 2018

Partial barriers to migration can affect migratory fish population dynamics and be influenced by many biotic, abiotic, and anthropogenic factors, including nutritional deficiencies. We investigated how such variables (including a thiamine deficiency) impact fine-scale movement of landlocked Atlantic salmon (Salmo salar) by treating returning spawners with thiamine and observing their attempts to climb a human-altered, high velocity stretch of river using fine-scale radio telemetry. Multiple re-entries into a river section, along with water temperature, strongly influenced movement rates. High or increasing discharge encouraged downstream movement; males abandoned migratory attempts at a higher rate than females. Although thiamine-injected salmon exhibited greater migratory duration, this did not produce a measurable improvement in passage performance, possibly due to the difficulty associated with this section of river — among 24 tagged salmon staging 10.9 attempts each and lasting 1.5 days per attempt on average, only three traversed the entire reach. This study provides new insights into how biotic and abiotic variables affect fish movement, while suggesting limits to the potential for human intervention (thiamine injections) to assist passage through partial migratory barriers.
Testing the differences of LT50, LD50, or ED50
Authors: Lappi Juha , Luoranen Jaana
Published: March 2018

An approximate method is derived for testing the differences of LT50, LD50, or ED50, which indicate the temperature or dose needed to kill or damage half of the plants, respectively. It is assumed that a logistic model is used to describe the relationship between probability and a treatment variable in the framework of generalized linear mixed models or generalized linear models. The method is based on the delta method and the Wald test. In the forest sciences, this method can be used when dose, temperature, or time responses are compared in different treatments, cultivars, or origins.
ARS leptogenesis
Authors: Drewes M. , Garbrecht B. , Hernández P. , Kekic M. , Lopez-Pavon J. , Racker J. , Rius N. , Salvado J. , Teresi D.
Published: March 2018

We review the current status of the leptogenesis scenario originally proposed by Akhmedov, Rubakov and Smirnov (ARS). It takes place in the parametric regime where the right-handed neutrinos are at the electroweak scale or below and the CP-violating effects are induced by the coherent superposition of different right-handed mass eigenstates. Two main theoretical approaches to derive quantum kinetic equations, the Hamiltonian time evolution as well as the Closed-Time-Path technique are presented, and we discuss their relations. For scenarios with two right-handed neutrinos, we chart the viable parameter space. Both, a Bayesian analysis, that determines the most likely configurations for viable leptogenesis given different variants of flat priors, and a determination of the maximally allowed mixing between the light, mostly left-handed, and heavy, mostly right-handed, neutrino states are discussed. Rephasing invariants are shown to be a useful tool to classify and to understand various distinct contributions to ARS leptogenesis that can dominate in different parametric regimes. While these analyses are carried out for the parametric regime where initial asymmetries are generated predominantly from lepton-number conserving, but flavor violating effects, we also review the contributions from lepton-number violating operators and identify the regions of parameter space where these are relevant.
Applying Periodic Thermal Management on Hard Real-Time Systems to Minimize Peak Temperature
Authors: Cheng Long , Huang Kai , Chen Gang , Hu Biao , Jiang Zhuangyi , Knoll Alois
Published: March 2018

Due to growing power density, on-chip temperature increases rapidly, which has hampered the reliability and performance of modern real-time systems. This paper studies how to minimize the peak temperature of real-time systems under hard real-time constraints with periodic thermal management. A closed-form representation of the peak temperature for such a periodic scheme is derived to tackle this problem. Based on this closed form and the arrival curve model, one offline approach and one online approach are proposed to minimize the peak temperature for a given event stream. The offline one does thermal optimization in design phase and introduces negligible runtime overhead. The online one computes dynamic power-control schemes which are adaptive to actual event arrivals and execution states. We conduct experiments on a real single-core processor and compare our approaches to two existing works. The temperature results measured from a physical thermal sensor demonstrate that the achieved maximal and average temperature reductions are 5[Formula: see text]K and 2.6[Formula: see text]K, respectively.
Bifurcation of Limit Cycles in a 12-Degree Hamiltonian System Under Thirteenth-Order Perturbation
Authors: Shi Jianping , Jiang Wentao
Published: March 2018

This paper considers the weakened Hilbert’s 16th problem for symmetric planar perturbed polynomial Hamiltonian system. A [Formula: see text]-equivariant planar vector field of degree 12 is deduced to find as many as possible limit cycles and their configuration patterns. By using bifurcation theory of planar dynamical system and the method of detection function, we have obtained that, under the thirteenth-order perturbation, the above [Formula: see text]-equivariant planar perturbed Hamiltonian vector field of 12-degree has at least 117 limit cycles. Moreover, this paper also shows the configuration of compound eyes of the corresponding perturbed systems.
Periodic Peakons, Pseudo-Peakons and Compactons of Ion-Acoustic Wave Model in Electronegative Plasmas with Electrons Featuring Tsallis Distribution
Authors: Li Jibin
Published: March 2018

The dynamical model of the nonlinear ion-acoustic oscillations is governed by a partial differential equation system. Its traveling system is just a singular traveling wave system of first class depending on four parameters. By using the method of dynamical systems and the theory of singular traveling wave systems, in this paper, we show that there exist parameter groups such that this singular system has pseudo-peakons, periodic peakons and compactons as well as kink and anti-kink wave solutions.
A Stochastic Pitchfork Bifurcation in Most Probable Phase Portraits
Authors: Wang Hui , Chen Xiaoli , Duan Jinqiao
Published: March 2018

We study stochastic bifurcation for a system under multiplicative stable Lévy noise (an important class of non-Gaussian noise), by examining the qualitative changes of equilibrium states with its most probable phase portraits. We have found some peculiar bifurcation phenomena in contrast to the deterministic counterpart: (i) When the non-Gaussianity parameter in Lévy noise varies, there is either one, two or no backward pitchfork type bifurcations; (ii) When a parameter in the vector field varies, there are two or three forward pitchfork bifurcations; (iii) The non-Gaussian Lévy noise clearly leads to fundamentally more complex bifurcation scenarios, since in the special case of Gaussian noise, there is only one pitchfork bifurcation which is reminiscent of the deterministic situation.
Buckling and Post-Buckling of Symmetric Functionally Graded Microplate Lying on Nonlinear Elastic Foundation Based on Modified Couple Stress Theory
Authors: Wu Chengyang , Lou Jia , He Liwen , Du Jianke , Wu Huaping
Published: March 2018

This paper is concerned with the buckling and post-buckling behaviors of a simply supported symmetric functionally graded (FG) microplate lying on a nonlinear elastic foundation. The modified couple stress theory is used to capture the size effects of the FG microplate, and the Mindlin plate theory with von Karman’s geometric nonlinearity taken into account is adopted to describe its deflection behavior. Based on these assumptions and the principle of minimum potential energy, the equilibrium equations of the FG microplate and associated boundary conditions are derived. By applying the Galerkin method to the equilibrium equations, closed-form solutions for the critical buckling load and the load–displacement relation in the post-buckling stage are obtained. Furthermore, the effects of the power law index, the material length scale parameter to thickness ratio, the stiffness of the elastic foundation, and in-plane boundary conditions on the buckling and post-buckling behaviors of the FG microplate are discussed in detail.
Automated Segmentation of Swine Skulls for Finite Element Model Creation Using High Resolution μ-CT Images
Authors: Zhu Zimo , Jones Donna C. , Liu G. R. , Soleimani Sajjad , Huang Xu , Shan Zhengyuan , Knorr Jacob , Caballero Montserrat , van Aalst John A.
Published: March 2018

Finite element (FE) analysis has been widely used to investigate bone responses to mechanical loading. Research in long bones has been straight forward because modeling of these bones requires only two material properties. Such an FE model may provide an adequate approximation of the anatomy for many cases. However, a more detailed model of skull bones is needed to accurately capture its complex structure of multiple bone pieces and the various mineral densities distributed throughout these bone pieces. Unfortunately, FE model development incorporating both complex geometries and anatomically accurate material properties is both computationally and labor intensive. In this study, a method is proposed to automatically segment micro-computed tomography ([Formula: see text]-CT) scan images of bone pieces to build an FE model of a full swine hemi-skull. Using the Digital Imaging and Communications in Medicine (DICOM) files from scanned bones, the complete geometry of each bone piece is recreated through seven customized processing algorithms. After assembling the bone pieces to form the skull, experimentally derived Young’s modulus values are correlated to grayscale values to produce a detailed FE model for accurate simulation. This detailed skull model can be used to predict strain/stress patterns in response to various loading regimes to facilitate research questions in fracture healing and growth, as well as bone tissue engineering and bone mineral density loss (e.g., osteoporosis).
On the Stability of Multi-Step Finite-Difference-Based Lattice Boltzmann Schemes
Authors: Krivovichev Gerasim V. , Mikheev Sergey A.
Published: March 2018

Stability of finite-difference-based off-lattice Boltzmann schemes is analyzed. The time derivative in system of discrete Boltzmann equations is approximated by two-step modified central difference. Advective term is approximated by finite differences from first- to fourth-orders of accuracy. Characteristics-based (CB) schemes and schemes with traditional separate approximations of space derivatives are considered. A special class of high-order CB schemes with approximation in the internal nodes of grid patterns is constructed. It is demonstrated that apparent viscosity for the schemes of high-order is equal to kinematic viscosity of the system of Bhatnaghar–Gross–Krook kinetic equations. Stability of the schemes is analyzed by the von Neumann method for the cases of two flow regimes in unbounded domain. Stability is analyzed by the investigation of the stability domains in parameter space. The area of the domain is considered as the main numerical characteristic of the stability. As the main result of the analysis, it must be mentioned that the areas of CB schemes are greater than areas for the schemes with separate approximations.
Towards Practical Guidelines for Conversion from Fixed to Reconfigurable Manufacturing Automation Systems
Authors: Coppini Alan , Saliba Michael A.
Published: March 2018

It is generally considered that economic feasibility of a reconfigurable manufacturing system (RMS) is only attainable if the system is defined to be reconfigurable at the outset of its design. In this work, we consider the potential exception to this perception, in the context of a common industrial scenario where a specialized and expensive manufacturing machine or system will otherwise be rendered useless due to the loss of business of the particular product being manufactured. Specific guidelines to convert from a fixed to a reconfigurable system are proposed, and evaluated through a case study. It is shown that under certain conditions, RMSs may be economically feasible even if they are developed through the modification of pre-existing dedicated systems.
Selective Cluster Presentation on the Search Results Page
Authors: Levi Or , Guy Ido , Raiber Fiana , Kurland Oren
Published: March 2018

Web search engines present, for some queries, a cluster of results from the same specialized domain (“vertical”) on the search results page (SERP). We introduce a comprehensive analysis of the presentation of such clusters from seven different verticals based on the logs of a commercial Web search engine. This analysis reveals several unique characteristics—such as size, rank, and clicks—of result clusters from community question-and-answer websites. The study of properties of this result cluster—specifically as part of the SERP—has received little attention in previous work. Our analysis also motivates the pursuit of a long-standing challenge in ad hoc retrieval, namely,
selective cluster retrieval
. In our setting, the specific challenge is to select for presentation the documents most highly ranked either by a cluster-based approach (those in the top-retrieved cluster) or by a document-based approach. We address this classification task by representing queries with features based on those utilized for ranking the clusters, query-performance predictors, and properties of the document-clustering structure. Empirical evaluation performed with TREC data shows that our approach outperforms a recently proposed state-of-the-art cluster-based document-retrieval method as well as state-of-the-art document-retrieval methods that do not account for inter-document similarities.
Electrochemical Probes of Microbial Community Behavior
Authors: Sismaet Hunter J. , Goluch Edgar D.
Published: March 2018

Advances in next-generation sequencing technology along with decreasing costs now allow the microbial population, or microbiome, of a location to be determined relatively quickly. This research reveals that microbial communities are more diverse and complex than ever imagined. New and specialized instrumentation is required to investigate, with high spatial and temporal resolution, the dynamic biochemical environment that is created by microbes, which allows them to exist in every corner of the Earth. This review describes how electrochemical probes and techniques are being used and optimized to learn about microbial communities. Described approaches include voltammetry, electrochemical impedance spectroscopy, scanning electrochemical microscopy, separation techniques coupled with electrochemical detection, and arrays of complementary metal-oxide-semiconductor circuits. Microbial communities also interact with and influence their surroundings; therefore, the review also includes a discussion of how electrochemical probes optimized for microbial analysis are utilized in healthcare diagnostics and environmental monitoring applications.
(Multi)functional Atomic Force Microscopy Imaging
Authors: Patel Anisha N. , Kranz Christine
Published: March 2018

Incorporating functionality to atomic force microscopy (AFM) to obtain physical and chemical information has always been a strong focus in AFM research. Modifying AFM probes with specific molecules permits accessibility of chemical information via specific reactions and interactions. Fundamental understanding of molecular processes at the solid/liquid interface with high spatial resolution is essential to many emerging research areas. Nanoscale electrochemical imaging has emerged as a complementary technique to advanced AFM techniques, providing information on electrochemical interfacial processes. While this review presents a brief introduction to advanced AFM imaging modes, such as multiparametric AFM and topography recognition imaging, the main focus herein is on electrochemical imaging via hybrid AFM-scanning electrochemical microscopy. Recent applications and the challenges associated with such nanoelectrochemical imaging strategies are presented.
Defining Adult Stem Cells by Function, not by Phenotype
Authors: Clevers Hans , Watt Fiona M.
Published: March 2018

Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.
Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism
Authors: Yang Wei , Gao Yang
Published: March 2018

The number of DNA polymerases identified in each organism has mushroomed in the past two decades. Most newly found DNA polymerases specialize in translesion synthesis and DNA repair instead of replication. Although intrinsic error rates are higher for translesion and repair polymerases than for replicative polymerases, the specialized polymerases increase genome stability and reduce tumorigenesis. Reflecting the numerous types of DNA lesions and variations of broken DNA ends, translesion and repair polymerases differ in structure, mechanism, and function. Here, we review the unique and general features of polymerases specialized in lesion bypass, as well as in gap-filling and end-joining synthesis.
Facet Joints of the Spine: Structure–Function Relationships, Problems and Treatments, and the Potential for Regeneration
Authors: O'Leary Siobhan A. , Paschos Nikolaos K. , Link Jarrett M. , Klineberg Eric O. , Hu Jerry C. , Athanasiou Kyriacos A.
Published: March 2018

The zygapophysial joint, a diarthrodial joint commonly referred to as the facet joint, plays a pivotal role in back pain, a condition that has been a leading cause of global disability since 1990. Along with the intervertebral disc, the facet joint supports spinal motion and aids in spinal stability. Highly susceptible to early development of osteoarthritis, the facet is responsible for a significant amount of pain in the low-back, mid-back, and neck regions. Current noninvasive treatments cannot offer long-term pain relief, while invasive treatments can relieve pain but fail to preserve joint functionality. This review presents an overview of the facet in terms of its anatomy, functional properties, problems, and current management strategies. Furthermore, this review introduces the potential for regeneration of the facet and particular engineering strategies that could be employed as a long-term treatment.
The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process
Authors: Hashem Yaser , Frank Joachim
Published: March 2018

Translation initiation in eukaryotes is a highly regulated and rate-limiting process. It results in the assembly and disassembly of numerous transient and intermediate complexes involving over a dozen eukaryotic initiation factors (eIFs). This process culminates in the accommodation of a start codon marking the beginning of an open reading frame at the appropriate ribosomal site. Although this process has been extensively studied by hundreds of groups for nearly half a century, it has been only recently, especially during the last decade, that we have gained deeper insight into the mechanics of the eukaryotic translation initiation process. This advance in knowledge is due in part to the contributions of structural biology, which have shed light on the molecular mechanics underlying the different functions of various eukaryotic initiation factors. In this review, we focus exclusively on the contribution of structural biology to the understanding of the eukaryotic initiation process, a long-standing jigsaw puzzle that is just starting to yield the bigger picture.
Stress, Telomeres, and Psychopathology: Toward a Deeper Understanding of a Triad of Early Aging
Authors: Epel Elissa S. , Prather Aric A.
Published: March 2018

Telomeres play an important part in aging and show relationships to lifetime adversity, particularly childhood adversity. Meta-analyses demonstrate reliable associations between psychopathology (primarily depression) and shorter telomere length, but the nature of this relationship has not been fully understood. Here, we review and evaluate the evidence for impaired telomere biology as a consequence of psychopathology or as a contributing factor, and the important mediating roles of chronic psychological stress and impaired allostasis. There is evidence for a triadic relationship among stress, telomere shortening, and psychiatric disorders that is positively reinforcing and unfolds across the life course and, possibly, across generations. We review the role of genetics and biobehavioral responses that may contribute to shorter telomere length, as well as the neurobiological impact of impaired levels of telomerase. These complex interrelationships are important to elucidate because they have implications for mental and physical comorbidity and, potentially, for the prevention and treatment of depression.
Treatment Selection in Depression
Authors: Cohen Zachary D. , DeRubeis Robert J.
Published: March 2018

Mental health researchers and clinicians have long sought answers to the question “What works for whom?” The goal of precision medicine is to provide evidence-based answers to this question. Treatment selection in depression aims to help each individual receive the treatment, among the available options, that is most likely to lead to a positive outcome for them. Although patient variables that are predictive of response to treatment have been identified, this knowledge has not yet translated into real-world treatment recommendations. The Personalized Advantage Index (PAI) and related approaches combine information obtained prior to the initiation of treatment into multivariable prediction models that can generate individualized predictions to help clinicians and patients select the right treatment. With increasing availability of advanced statistical modeling approaches, as well as novel predictive variables and big data, treatment selection models promise to contribute to improved outcomes in depression.
Medical Technologies and Challenges of Robot-Assisted Minimally Invasive Intervention and Diagnostics
Authors: Simaan Nabil , Yasin Rashid M. , Wang Long
Published: March 2018

Emerging paradigms furthering the reach of medical technology into human anatomy present unique modeling, control, and sensing problems. This review provides a brief history of medical robotics, leading to the current trend of minimally invasive intervention and diagnostics in confined spaces. We discuss robotics for natural orifice and single-port access surgery, capsule and magnetically actuated robotics, and microrobotics, with the aim of elucidating the state of the art. We also discuss works on modeling, sensing, and control of mechanical architectures of robots for natural orifice and single-port access surgery, followed by works on magnetic actuation, sensing, and localization for capsule robotics and microrobotics. Finally, we present challenges and open problems in each of these areas.
Biliverdin reductase and bilirubin in hepatic disease
Authors: Weaver Lauren , Hamoud Abdul-rizaq , Stec David E. , Hinds Terry D.
Published: March 2018

The buildup of fat in the liver (hepatic steatosis) is the first step in a series of incidents that may drive hepatic disease. Obesity is the leading cause of nonalcoholic fatty liver disease (NAFLD), in which hepatic steatosis progresses to liver disease. Chronic alcohol exposure also induces fat accumulation in the liver and shares numerous similarities to obesity-induced NAFLD. Regardless of whether hepatic steatosis is due to obesity or long-term alcohol use, it still may lead to hepatic fibrosis, cirrhosis, or possibly hepatocellular carcinoma. The antioxidant bilirubin and the enzyme that generates it, biliverdin reductase A (BVRA), are components of the heme catabolic pathway that have been shown to reduce hepatic steatosis. This review discusses the roles for bilirubin and BVRA in the prevention of steatosis, their functions in the later stages of liver disease, and their potential therapeutic application.
Effects of triceps surae muscle strength and tendon stiffness on the reactive dynamic stability and adaptability of older female adults during perturbed walking
Authors: Epro Gaspar , McCrum Christopher , Mierau Andreas , Leyendecker Michael , Brüggemann Gert-Peter , Karamanidis Kiros
Published: March 2018

This study aimed to examine whether the triceps surae (TS) muscle-tendon unit (MTU) mechanical properties affect gait stability and its reactive adaptation potential to repeated perturbation exposure in older adults. Thirty-four older adults each experienced eight separate unexpected perturbations during treadmill walking, while a motion capture system was used to determine the margin of stability (MoS) and base of support (BoS). Ankle plantar flexor muscle strength and Achilles tendon (AT) stiffness were analyzed using ultrasonography and dynamometry. A median split and separation boundaries classified the subjects into two groups with GroupStrong ( n = 10) showing higher ankle plantar flexor muscle strength (2.26 ± 0.17 vs. 1.47 ± 0.20 N·m/kg, means ± SD; P < 0.001) and AT stiffness (544 ± 75 vs. 429 ± 86 N/mm; P = 0.004) than GroupWeak ( n = 12). The first perturbation caused a negative ΔMoS (MoS in relation to unperturbed baseline walking) at touchdown of perturbed step (PertR), indicating an unstable position. GroupStrong required four recovery steps to return to ΔMoS zero level, whereas GroupWeak was unable to return to baseline within the analyzed steps. However, after repeated perturbations, both groups increased ΔMoS at touchdown of PertR with a similar magnitude. Significant correlations between ΔBoS and ΔMoS at touchdown of the first recovery step and TS MTU capacities (0.41 < r < 0.57; 0.006 < P < 0.048) were found. We conclude that older adults with TS muscle weakness have a diminished ability to control gait stability during unexpected perturbations, increasing their fall risk, but that degeneration in muscle strength and tendon stiffness may not inhibit the ability of the locomotor system to adapt the reactive motor response to repeated perturbations.

NEW & NOTEWORTHY Triceps surae muscle weakness and a more compliant Achilles tendon partly limit older adults’ ability to effectively enlarge the base of support and recover dynamic stability after an unexpected perturbation during walking, increasing their fall risk. However, the degeneration in muscle strength and tendon stiffness may not inhibit the ability of the locomotor system to adapt the reactive motor response to repeated perturbations.
An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury
Authors: Nelissen Jules L. , Traa Willeke A. , de Boer Hans H. , de Graaf Larry , Mazzoli Valentina , Savci-Heijink C. Dilara , Nicolay Klaas , Froeling Martijn , Bader Dan L. , Nederveen Aart J. , Oomens Cees W. J. , Strijkers Gustav J.
Published: March 2018

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T2, T2*, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2 corresponded with edema, muscle cell damage, and inflammation. T2* was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue’s microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage.

NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.
Respiratory pump maintains cardiac stroke volume during hypovolemia in young, healthy volunteers
Authors: Skytioti Maria , Søvik Signe , Elstad Maja
Published: March 2018

Spontaneous breathing has beneficial effects on the circulation, since negative intrathoracic pressure enhances venous return and increases cardiac stroke volume. We quantified the contribution of the respiratory pump to preserve stroke volume during hypovolemia in awake, young, healthy subjects. Noninvasive stroke volume, cardiac output, heart rate, and mean arterial pressure (Finometer) were recorded in 31 volunteers (19 women), 19–30 yr old, during normovolemia and hypovolemia (approximating 450- to 500-ml reduction in central blood volume) induced by lower-body negative pressure. Control-mode noninvasive positive-pressure ventilation was employed to reduce the effect of the respiratory pump. The ventilator settings were matched to each subject’s spontaneous respiratory pattern. Stroke volume estimates during positive-pressure ventilation and spontaneous breathing were compared with Wilcoxon matched-pairs signed-rank test. Values are overall medians. During normovolemia, positive-pressure ventilation did not affect stroke volume or cardiac output. Hypovolemia resulted in an 18% decrease in stroke volume and a 9% decrease in cardiac output ( P < 0.001). Employing positive-pressure ventilation during hypovolemia decreased stroke volume further by 8% ( P < 0.001). Overall, hypovolemia and positive-pressure ventilation resulted in a reduction of 26% in stroke volume ( P < 0.001) and 13% in cardiac output ( P < 0.001) compared with baseline. Compared with the situation with control-mode positive-pressure ventilation, spontaneous breathing attenuated the reduction in stroke volume induced by moderate hypovolemia by 30% (i.e., −26 vs. −18%). In the patient who is critically ill with hypovolemia or uncontrolled hemorrhage, spontaneous breathing may contribute to hemodynamic stability, whereas controlled positive-pressure ventilation may result in circulatory decompensation.

NEW & NOTEWORTHY Maintaining spontaneous respiration has beneficial effects on hemodynamic compensation, which is clinically relevant for patients in intensive care. We have quantified the contribution of the respiratory pump to cardiac stroke volume and cardiac output in healthy volunteers during normovolemia and central hypovolemia. The positive hemodynamic effect of the respiratory pump was abolished by noninvasive, low-level positive-pressure ventilation. Compared with control-mode positive-pressure ventilation, spontaneous negative-pressure ventilation attenuated the fall in stroke volume by 30%.
Detecting and Identifying Industrial Gases by a Method Based on Olfactory Machine at Different Concentrations
Authors: Sun Yunlong , Luo Dehan , Li Hui , Zhu Chuchu , Xu Ou , Gholam Hosseini Hamid
Published: March 2018

Gas sensors have been widely reported for industrial gas detection and monitoring. However, the rapid detection and identification of industrial gases are still a challenge. In this work, we measure four typical industrial gases including CO2, CH4, NH3, and volatile organic compounds (VOCs) based on electronic nose (EN) at different concentrations. To solve the problem of effective classification and identification of different industrial gases, we propose an algorithm based on the selective local linear embedding (SLLE) to reduce the dimensionality and extract the features of high-dimensional data. Combining the Euclidean distance (ED) formula with the proposed algorithm, we can achieve better classification and identification of four kinds of gases. We compared the classification and recognition results of classical principal component analysis (PCA), linear discriminate analysis (LDA), and PCA + LDA algorithms with the proposed SLLE algorithm after selecting the original data and performing feature extraction. The experimental results show that the recognition accuracy rate of the SLLE reaches 91.36%, which is better than the other three algorithms. In addition, the SLLE algorithm provides more efficient and accurate responses to high-dimensional industrial gas data. It can be used in real-time industrial gas detection and monitoring combined with gas sensor networks.