bluuebunny/crossref_metadata_2025 huggingface dataset:
Agar pre-embedding of small skin biopsies: real-life benefits and challenges in high throughput pathology laboratories
Authors: Ridolfi Mara , Paudice Michele , Salvi Sandra , Valle Luca , Gualco Marina , Perasole Antonio , Anselmi Luca , Fiocca Roberto , Mastracci Luca , Grillo Federica
Published: February 2019

Paraffin embedding of small, thin tissue samples requires specific expertise for optimal orientation before tissue sectioning. This study evaluates the real-life utility of the agar pre-embedding technique for small skin biopsies with regards to lengthening of work times, problems in orientation (re-embedding) and ancillary techniques (immunohistochemistry and in situ hybridisation) between two high work flow pathology laboratories, one of which routinely uses the agar pre-embedding technique and one which does not. The mean time required for pre-embedding in agar was 30.4 s, but time for paraffin embedding for agar pre-embedded samples was shorter than the traditional method (177 vs 296 s; p<0.005). The number of skin samples requiring re-embedding was significantly higher with the traditional embedding method (p<0.005). No problems in immunoreactivity were observed in all 1900 reactions performed with 17 different antibodies. Fluorescence in situ hybridisation analysis was optimised with a prolonged protease K incubation time (21 vs 18 min).
Detection ofEGFRmutations using target capture sequencing in plasma of patients with non-small-cell lung cancer
Authors: Bai Hao , Xia Jinjing , Zhao Xiaokai , Gong Ziying , Zhang Daoyun , Xiong liwen
Published: February 2019

Purpose 

Circulating tumour DNA (ctDNA) is a promising biomarker for detection of non-invasive epidermal growth factor receptor(EGFR) mutations in patients with non-small-cell lung cancer (NSCLC). However, the existing methods have limitations in sensitivity or in availability. The aim was to evaluate the accuracy of capture target sequencing for detectingEGFRmutations in ctDNA.

Methods 

A total of 79 patients with NSCLC and available plasma and matched tissue specimens were enrolled. Through capture target sequencing, mutations were searched in over 20 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. To evaluate the accuracy, detection ofEGFRmutations in matched tissue samples was performed by target capture sequencing and the amplification refractory mutation system (ARMS).

Results 

EGFRmutations were discovered in 32.9 % (26/79) of the patients with NSCLC, the overall rate of consistency for the 79 paired plasma and tissue samples was 86.1 % (68/79). The sensitivity and specificity of detectingEGFRmutations in the plasma were 72.7 % and 95.7 %. In terms of theEGFRmutations identified by ARMS, the overall consistency was 78.5 % (62/79) in three groups. Of 21 patients withEGFRsensitive mutation defined by next generation sequencing in ctDNA, 20 (95.2%) showed long-term disease control with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment; the median progression-free survival was 10.8 months (95% CI 9.1 to 16.8).

Conclusions

Target capture sequencing of ctDNA can be used for genotyping ofEGFRin patients with NSCLC, which may enable a direct recommendation for EGFR TKI on the basis of positive results with plasma DNA.
Mevalonate Signaling, COPD and Cancer: The Statins and Beyond
Authors: Hopkins Raewyn J , Young Robert P
Published: February 2019

Evidence suggests that smoking confers a persistent and/or exaggerated inflammatory response in the lungs that, with underlying genetic susceptibility, may result in lung remodeling and impaired repair. The innate immune response to smoking described above, which is modified by the mevalonate pathway, provides a plausible pathogenic link between the development of chronic obstructive pulmonary disease and lung cancer. The mevalonate pathway modifies innate responsiveness through important intracellular signaling molecules called guanine phosphate transferases (GTPases) such as Rho-A. Smoke exposure activates cell surface proteins which, through the mediating influence of GTPases, then modifies the activation of nuclear factor kappa -light-chain-enhancer of activated B cells (NFκB) its downstream effects on genes underlying innate immunity, neutrophilic inflammation and carcinogenesis. The mevalonate pathway is modifiable through the enzyme 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMGCo-A) reductase. This enzyme controls the rate limiting step of the mevalonate pathway and is subject to inhibition by statin drugs (HMGCo-A reductase inhibitors) and small chain fatty acids derived from high dietary fiber intake. Ths, inhibitory effect dampens the innate immune response to smoking and may modify pulmonary inflammation and lung remodeling. This article is a symposia summary outlining the preclinical and clinical data suggesting that statins and a high-fiber diet may have a chemopreventive effect on lung cancer.
Constitutive reduction in the checkpoint inhibitor, CTLA-4, does not accelerate SLE in NZM 2328 mice
Authors: Stohl William , Yu Ning , Chalmers Samantha A , Putterman Chaim , Jacob Chaim O
Published: February 2019

Background/objective

Treatment with immune checkpoint inhibitors (ICIs) in oncology patients is increasing. Although ICIs trigger rheumatic immune-related adverse events, development of SLE features has been rare. Whether long-term treatment with ICIs would promote SLE features remains unknown. To begin to address this, we generated SLE-prone NZM 2328 mice with lifelong reduction in CTLA-4 expression.

Methods

Since CTLA-4-deficient (Ctla4−/−) NZM mice developed a lethal lymphoproliferative disorder by 3–6 weeks of age, development of SLE in these mice could not be studied.Ctla4haploinsufficient NZM.Ctla4+/−mice were assessed in parallel with littermate female NZM.Ctla4+/+mice. Evaluations included CTLA-4 expression and lymphocyte profiles, assessed by fluorescence-activated cell sorting; serological profiles, assessed by ELISA; renal immunopathology, assessed by histology and immunofluorescence; and clinical courses, assessed by mortality.

Results

CTLA-4 expression was lower in NZM.Ctla4+/−mice than in NZM.Ctla4+/+mice. Spleen mononuclear cells, B cells, plasma cells, CD4+cells, recently activated CD4+cells and CD4+T regulatory (Treg) cells were increased in NZM.Ctla4+/−mice (p≤0.042). The serological profile, degree of renal immunopathology and mortality in NZM.Ctla4+/−mice remained unaffected.

Conclusion

Lifelong reduction in CTLA-4 expression in NZM mice neither accelerated nor aggravated SLE. Expansion in Treg cells may have played a protective role. Our observations raise the hope that long-term treatment of patients with SLE with an anti-CTLA-4 agent, should the need arise, would not adversely affect SLE disease activity.
“Residents get no… satisfaction”a problem to face during internal medicine rotations: development and psychometric properties of the IMPRINT-15
Authors: Díaz Luis Antonio , Sepúlveda Paola , Abbott Eduardo , Fuentes-López Eduardo , Letelier Luz María , Riquelme Arnoldo , Aizman Andrés
Published: February 2019

Clinical rotations are an essential part of Internal Medicine (IM) residency programmes, where curricular objectives are carried out. To our knowledge, there are no validated instruments to assess IM clinical rotations. Our objective was to develop an instrument for residents to assess the quality of clinical rotations in an IM residency programme, and to test the psychometric properties of the instrument. A mixed methodology was used, including qualitative and quantitative phases. Items were proposed by a group of experts based on previously identified residency needs, followed by a quantitative phase to generate consensus among educators and residents to define which items would be included in the instrument (Delphi panel). After generating the instrument, psychometric tests were performed to assess construct validity (factor analysis) and reliability (Raykov’s reliability coefficient). We obtained a 15-item instrument after two Delphi rounds: Internal Medicine Program Instrument 15-items (IMPRINT-15). Sixty-two residents answered 428 surveys using a Likert scale during 7 months (response rate 98.9%). The median score was 4.3 (IQR 3.9–4.7) (scale from 1 to 5). The factor analysis showed two domains in the clinical rotation assessment: (1) teaching and care activities; (2) evaluation and feedback. The instrument is reliable with Raykov’s reliability coefficient of 0.86. Also, Raykov’s reliability coefficient for the domains were 0.89 and 0.83, respectively. The IMPRINT-15 instrument is a bi-dimensional, valid and reliable questionnaire to evaluate the perceived quality by residents of the IM clinical rotations. Also, it constitutes the first validated instrument in this field worldwide.
A low-calorie diet with or without interval exercise training improves adiposopathy in obese women
Authors: Gilbertson Nicole M. , Eichner Natalie Z.M. , Heiston Emily M. , Gaitán Julian M. , Francois Monique E. , Mehaffey J. Hunter , Hassinger Taryn E. , Hallowell Peter T. , Weltman Arthur , Malin Steven K.
Published: February 2019

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) improves adiposopathy, an endocrine dysfunction, when compared with an energy-deficit–matched LCD in obese women. Subjects (age: 48.2 ± 2.4 years, body mass index: 37.8 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 12; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate). Exercise was estimated to expend 350 kcal per oxygen uptake–heart rate regression analysis and individuals were refed calories expended to match energy availability between groups. Absolute (post – pre caloric intake) and relative (total daily and exercise energy expenditure relative to calorie intake) energy deficits were calculated. Fitness (peak oxygen uptake) and body composition (BodPod; Cosmed USA Inc.) were measured and a 120-min, 75g oral glucose tolerance test was performed at pre- and post-intervention to assess adiposopathy (i.e., ratio of high molecular weight–adiponectin to leptin) and estimate insulin sensitivity. LCD and LCD+INT had similar absolute (P = 0.55) and relative (P = 0.76) energy deficits. LCD and LCD+INT had similar reductions in fat mass (both P < 0.001), despite LCD inducing greater weight loss (P = 0.02) than LCD+INT. Both treatments improved adiposopathy (P = 0.003) and peripheral insulin sensitivity (P = 0.02). Absolute energy deficit correlated to improved adiposopathy (r = –0.41, P = 0.05), and absolute and relative energy deficits were associated with increased insulin sensitivity (r = –0.47, P = 0.02; and r = –0.40, P = 0.05, respectively), independent of body composition changes and increased peak oxygen uptake. Taken together, LCD, with or without INT, improves adiposopathy in relation to insulin sensitivity in obese women, suggesting that a short-term energy deficit is key for reducing risk of type 2 diabetes.
Experimental culling of minnows suppresses cyanobacterial bloom under low-nutrient conditions
Authors: Stuparyk Blake R. , Graham Mark , Cook Jenna , Johnsen Mitchell A. , Christensen-Dalsgaard Karen K. , Vinebrooke Rolf D.
Published: February 2019

Cyanobacterial blooms in lakes of low nutrient status are recent ecological surprises. Culling of planktivorous fish may help suppress phytoplankton blooms via a trophic cascade effect. To test this hypothesis, we conducted a 90-day experiment adjacent to a shallow oligomesotrophic lake increasingly beset by midsummer cyanobacterial blooms in the presence of high abundances of minnows and sparse herbivorous zooplankton. The single-factor (± three spottail shiners, Notropis hudsonius) experimental design was replicated 10 times for a total of twenty 1200 L capacity mesocosms. Contrary to the trophic cascade hypothesis, minnow removal decreased the abundance of bosminids capable of grazing cyanobacteria. Nevertheless, removal of the minnows significantly both suppressed phytoplankton biomass and offset the development of cyanobacteria, such as Gloeotrichia echinulata. Lower concentrations of phosphorus and nitrogen in the fishless relative to stocked mesocosms best explained these differences in the phytoplankton community. Our findings highlight how fisheries management practices that enhance minnow populations in lakes of low productivity may inadvertently contribute to cyanobacterial blooms through increased nutrient cycling.
Mechanisms of Sensory Discrimination: Insights fromDrosophilaOlfaction
Authors: Groschner Lukas N. , Miesenböck Gero
Published: February 2019

All an animal can do to infer the state of its environment is to observe the sensory-evoked activity of its own neurons. These inferences about the presence, quality, or similarity of objects are probabilistic and inform behavioral decisions that are often made in close to real time. Neural systems employ several strategies to facilitate sensory discrimination: Biophysical mechanisms separate the neuronal response distributions in coding space, compress their variances, and combine information from sequential observations. We review how these strategies are implemented in the olfactory system of the fruit fly. The emerging principles of odor discrimination likely apply to other neural circuits of similar architecture.
Man and the Microbiome: A New Theory of Everything?
Authors: Butler Mary I. , Cryan John F. , Dinan Timothy G.
Published: February 2019

The gut microbiome is implicated in the pathophysiology of a wide range of psychological disorders. Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut–brain communication. There are many signaling pathways involved, including the hypothalamic–pituitary–adrenal axis, immune modulation, tryptophan and serotonin metabolism, bile acid transformation, microbial production of neuroactive compounds, and regulation of the endocannabinoid system. The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person's microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.
Erythropoietin inhalation enhances adult canine alveolar-capillary formation following pneumonectomy
Authors: Dane D. Merrill , Yilmaz Cuneyt , Gyawali Dipendra , Iyer Roshni , Menon Jyothi , Nguyen Kytai T. , Ravikumar Priya , Estrera Aaron S. , Hsia Connie C. W.
Published: February 2019

Paracrine erythropoietin (EPO) signaling in the lung recruits endothelial progenitor cells, promotes cell maturation and angiogenesis, and is upregulated during canine postpneumonectomy (PNX) compensatory lung growth. To determine whether inhalational delivery of exogenous EPO augments endogenous post-PNX lung growth, adult canines underwent right PNX and received, via a permanent tracheal stoma, weekly nebulization of recombinant human EPO-containing nanoparticles or empty nanoparticles (control) for 16 wk. Lung function was assessed under anesthesia pre- and post-PNX. The remaining lobes were fixed for detailed morphometric analysis. Compared with control treatment, EPO delivery significantly increased serum EPO concentration without altering systemic hematocrit or hemoglobin concentration and abrogated post-PNX lipid oxidative stress damage. EPO delivery modestly increased post-PNX volume densities of the alveolar septum per unit of lung volume and type II epithelium and endothelium per unit of septal tissue volume in selected lobes. EPO delivery also augmented the post-PNX increase in alveolar double-capillary profiles, a marker of intussusceptive capillary formation, in all remaining lobes. EPO treatment did not significantly alter absolute resting lung volumes, lung and membrane diffusing capacities, alveolar-capillary blood volume, pulmonary blood flow, lung compliance, or extravascular alveolar tissue volumes or surface areas. Results established the feasibility of chronic inhalational delivery of growth-modifying biologics in a large animal model. Exogenous EPO selectively enhanced cytoprotection and alveolar angiogenesis in remaining lobes but not whole-lung extravascular tissue growth or resting function; the nonuniform response contributes to structure-function discrepancy, a major challenge for interventions aimed at amplifying the innate potential for compensatory lung growth.
Time-resolved quantification of the dynamic extracellular space in the brain during short-lived event: methodology and simulations
Authors: Chen Kevin C. , Zhou Yi , Zhao Hui-Hui
Published: February 2019

Two macroscopic parameters describe the interstitial diffusion of substances in the extracellular space (ECS) of the brain, the ECS volume fraction α and the diffusion tortuosity λ. Past methods based on sampling the extracellular concentration of a membrane-impermeable ion tracer, such as tetramethylammonium (TMA+), can characterize either the dynamic α( t) alone or the constant α and λ in resting state but never the dynamic α( t) and λ( t) simultaneously in short-lived brain events. In this work, we propose to use a sinusoidal method of TMA+to provide time-resolved quantification of α( t) and λ( t) in acute brain events. This method iontophoretically injects TMA+in the brain ECS by a sinusoidal time pattern, samples the resulting TMA+diffusion waveform at a distance, and analyzes the transient modulations of the amplitude and phase lag of the sampled TMA+waveform to infer α( t) and λ( t). Applicability of the sinusoidal method was verified through computer simulations of the sinusoidal TMA+diffusion waveform in cortical spreading depression. Parameter sensitivity analysis identified the sinusoidal frequency and the interelectrode distance as two key operating parameters. Compared with other TMA+-based methods, the sinusoidal method can more accurately capture the dynamic α( t) and λ( t) in acute brain events and is equally applicable to other pathological episodes such as epilepsy, transient ischemic attack, and brain injury. Future improvement of the method should focus on high-fidelity extraction of the waveform amplitude and phase angle.

NEW & NOTEWORTHY An iontophoretic sinusoidal method of tetramethylammonium is described to capture the dynamic brain extracellular space volume fraction α and diffusion tortuosity λ. The sinusoidal frequency and interelectrode distance are two key operating parameters affecting the method’s accuracy in capturing α( t) and λ( t). High-fidelity extraction of the waveform amplitude and phase lag is critical to successful sinusoidal analyses.
Planning face, hand, and leg movements: anatomical constraints on preparatory inhibition
Authors: Labruna Ludovica , Tischler Claudia , Cazares Christian , Greenhouse Ian , Duque Julie , Lebon Florent , Ivry Richard B.
Published: February 2019

Motor-evoked potentials (MEPs), elicited by transcranial magnetic stimulation (TMS) over the motor cortex, are reduced during the preparatory period in delayed response tasks. In this study we examined how MEP suppression varies as a function of the anatomical organization of the motor cortex. MEPs were recorded from a left index muscle while participants prepared a hand or leg movement in experiment 1 or prepared an eye or mouth movement in experiment 2. In this manner, we assessed if the level of MEP suppression in a hand muscle varied as a function of the anatomical distance between the agonist for the forthcoming movement and the muscle targeted by TMS. MEP suppression was attenuated when the cued effector was anatomically distant from the hand (e.g., leg or facial movement compared with finger movement). A similar effect was observed in experiment 3 in which MEPs were recorded from a muscle in the leg and the forthcoming movement involved the upper limb or face. These results demonstrate an important constraint on preparatory inhibition: it is sufficiently broad to be manifest in a muscle that is not involved in the task, but it is not global, showing a marked attenuation when the agonist muscle belongs to a different segment of the body.

NEW & NOTEWORTHY Using transcranial magnetic stimulation, we examined changes in corticospinal excitability as people prepared to move. Consistent with previous work, we observed a reduction in excitability during the preparatory period, an effect observed in both task-relevant and task-irrelevant muscles. However, this preparatory inhibition is anatomically constrained, attenuated in muscles belonging to a different body segment than the agonist of the forthcoming movement.
Parallel distributed networks resolved at high resolution reveal close juxtaposition of distinct regions
Authors: Braga Rodrigo M. , Van Dijk Koene R. A. , Polimeni Jonathan R. , Eldaief Mark C. , Buckner Randy L.
Published: February 2019

Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the “default network,” comprises two closely interdigitated networks, only one of which is coupled to posterior parahippocampal cortex. Not all studies of individuals have identified the same networks, and questions remain about the degree to which the two networks are separate, particularly within regions hypothesized to be interconnected hubs. In this study we replicate the observation of network separation across analytical (seed-based connectivity and parcellation) and data projection (volume and surface) methods in two individuals each scanned 31 times. Additionally, three individuals were examined with high-resolution (7T; 1.35 mm) functional magnetic resonance imaging to gain further insight into the anatomical details. The two networks were identified with separate regions localized to adjacent portions of the cortical ribbon, sometimes inside the same sulcus. Midline regions previously implicated as hubs revealed near complete spatial separation of the two networks, displaying a complex spatial topography in the posterior cingulate and precuneus. The network coupled to parahippocampal cortex also revealed a separate region directly within the hippocampus, at or near the subiculum. These collective results support that the default network is composed of at least two spatially juxtaposed networks. Fine spatial details and juxtapositions of the two networks can be identified within individuals at high resolution, providing insight into the network organization of association cortex and placing further constraints on interpretation of group-averaged neuroimaging data.

NEW & NOTEWORTHY Recent evidence has emerged that canonical large-scale networks such as the “default network” fractionate into parallel distributed networks when defined within individuals. This research uses high-resolution imaging to show that the networks possess juxtapositions sometimes evident inside the same sulcus and within regions that have been previously hypothesized to be network hubs. Distinct circumscribed regions of one network were also resolved in the hippocampal formation, at or near the parahippocampal cortex and subiculum.
Characterization and Optimization of the Seeding Process of Adipose Stem Cells on the Polycaprolactone Scaffolds
Authors: Kurzyk Agata , Ostrowska Barbara , Święszkowski Wojciech , Pojda Zygmunt
Published: February 2019

The purpose of the current study was to evaluate the usefulness of adipose-derived stem cells (ASCs) for bone injury therapy. Lipoaspirates were collected from the abdomen regions of 17 healthy female donors (mean age 49 ± 6 years) using Coleman technique or Body-jet liposuction. In the present study, the primary objective was the in vitro characteristics of human ASCs. The secondary objective was the optimization of the cell seeding process on 3D-printed scaffolds using polycaprolactone (PCL) or polycaprolactone covered with tricalcium phosphate (PCL + 5% TCP). Biological evaluation of human ASC showed high efficiency of isolation obtaining a satisfying amount of homogeneous cell populations. Results suggest that ASCs can be cultured in vitro for a long time without impairing their proliferative capacity. Growth kinetics shows that the highest number of cells can be achieved in passage 5 and after the 16th passage; there is a significant decrease of cell numbers and their proliferative potential. The percentage of colony forming units from the adipose stem cells is 8% ± 0.63% (p<0.05). It was observed that the accumulation of calcium phosphate in the cells in vitro, marked with Alizarin Red S, was increased along with the next passage. Analysis of key parameters critically related to the cell seeding process shows that volume of cell suspension and propagation time greatly improve the efficiency of seeding both in PCL and PCL + 5% TCP scaffolds. The cell seeding efficiency did differ significantly between scaffold materials and cell seeding methods (p<0.001). Increased seeding efficiency was observed when using the saturation of cell suspension into scaffolds with additional incubation. Alkaline phosphatase level production in PCL + 5% TCP scaffold was better than in PCL-only scaffold. The study results can be used for the optimization of the seeding process and quantification methods determining the successful implementation of the preclinical model study in the future tissue engineering strategies.
Behaviour of Rubberized Concrete Short Columns Confined by Aramid Fibre Reinforced Polymer Jackets Subjected to Compression
Authors: Oprişan Gabriel , Enţuc Ioana-Sorina , Mihai Petru , Toma Ionuţ-Ovidiu , Ţăranu Nicolae , Budescu Mihai , Munteanu Vlad
Published: February 2019

The paper presents experimental and numerical investigations on the behaviour of rubberized concrete short columns confined with aramid fibre reinforced polymer (AFRP) subjected to compression. Additionally, the possibilities to substitute fine aggregate with crumb rubber granules, obtained from discarded worn tires, in structural concrete is also assessed. Because replacing traditional concrete aggregates by rubber particles leads to a significant loss in compressive strength, the authors highlight the use of AFRP confinement to partially or fully restore the compressive strength by applying a number of 1, 2, and 3 layers. Analytical models available for confined regular concrete are used to predict the peak stresses and the corresponding peak strains. Some analytical models give accurate results in terms of peak stress while others better approximate the ultimate strain. The full stress‐strain curve of rubberized concrete and the experimentally obtained values for the material properties of AFRP are used as input data for the numerical modelling. A good agreement is found between the results obtained for the peak stress and corresponding axial strain from both the numerical simulations and the experimental investigations.
ECG Signal Denoising and Features Extraction Using Unbiased FIR Smoothing
Authors: Lastre-Domínguez Carlos , Shmaliy Yuriy S. , Ibarra-Manzano Oscar , Munoz-Minjares Jorge , Morales-Mendoza Luis J.
Published: February 2019

Methods of the electrocardiography (ECG) signal features extraction are required to detect heart abnormalities and different kinds of diseases. However, different artefacts and measurement noise often hinder providing accurate features extraction. One of the standard techniques developed for ECG signals employs linear prediction. Referring to the fact that prediction is not required for ECG signal processing, smoothing can be more efficient. In this paper, we employ the p-shift unbiased finite impulse response (UFIR) filter, which becomes smooth by p<0. We develop this filter to have an adaptive averaging horizon: optimal for slow ECG behaviours and minimal for fast excursions. It is shown that the adaptive UFIR algorithm developed in such a way provides better denoising and suboptimal features extraction in terms of the output signal-noise ratio (SNR). The algorithm is developed to detect durations and amplitudes of the P-wave, QRS-complex, and T-wave in the standard ECG signal map. Better performance of the algorithm designed is demonstrated in a comparison with the standard linear predictor, UFIR filter, and UFIR predictive filter based on real ECG data associated with normal heartbeats.
The Association of Olfactory Dysfunction, Frailty, and Mortality Is Mediated by Inflammation: Results from the InCHIANTI Study
Authors: Laudisio Alice , Navarini Luca , Margiotta Domenico Paolo Emanuele , Fontana Davide Onofrio , Chiarella Irene , Spitaleri Daniele , Bandinelli Stefania , Gemma Antonella , Ferrucci Luigi , Incalzi Raffaele Antonelli
Published: February 2019

Background. Olfactory dysfunction might unveil the association between ageing and frailty, as it is associated with declining cognitive function, depression, reduced physical performance, reduced dietary intake, and mortality; all these conditions are characterized by increased levels of inflammatory parameters. The present study is aimed at evaluating the association between olfactory dysfunction, frailty, and mortality and whether such association might be mediated by inflammation. Methods. We analysed data of 1035 participants aged 65+ enrolled in the “InCHIANTI” study. Olfactory function was tested by the recognition of the smells of coffee, mint, and air. Olfactory dysfunction was defined as lack of recognition of at least two smells. Considering the items “shrinking,” “exhaustion,” “sedentariness,” “slowness,” and “weakness” included in the Fried definition, frailty was defined as the presence of at least three criteria, prefrailty of one or two, and robustness of none. Serum interleukin-6 (IL-6) was measured in duplicate by high-sensitivity enzyme-linked immunosorbent assays. Logistic regression was adopted to assess the association of frailty with olfactory function, as well as with the increasing number of olfactory deficits. Cox regression was used to test the association between olfactory dysfunction and 9-year survival. Results. Olfactory dysfunction was associated with frailty, after adjusting (OR 1.94, 95% CI=1.07-3.51; P=.028); analysis of the interaction term indicated that the association varied according to interleukin-6 levels (P for interaction=.005). Increasing levels of olfactory dysfunction were associated with increasing probability of being frail. Also, olfactory dysfunction was associated with reduced survival (HR 1.52, 95% CI=1.16-1.98; P=.002); this association varied according to the presence of frailty (P for interaction=.017) and prefrailty status (P for interaction=.046), as well as increased interleukin-6 levels (P for interaction = .011). Conclusions. Impairment of olfactory function might represent a marker of frailty, prefrailty, and consequently reduced survival in an advanced age. Inflammation might represent the possible link between these conditions.
The Relationship between Carotid Intima-Media Thickness and Ocular Circulation in Type-2 Diabetes
Authors: Ichinohasama Kohei , Kunikata Hiroshi , Ito Azusa , Yasuda Masayuki , Sawada Shojiro , Kondo Keiichi , Satake Chihiro , Katagiri Hideki , Nakazawa Toru
Published: February 2019

Purpose. To compare clinical findings, including ocular blood flow and intima-media thickness (IMT) of the carotid artery, in mild nonproliferative diabetic retinopathy (NPDR) and no diabetic retinopathy (NDR) patients, and to determine risk factors contributing to mild NPDR.Methods. In 129 subjects (129 eyes) with type-2 diabetes patients and mild NPDR or NDR, standard statistical techniques were used to determine associations between clinical findings, including diabetes duration, blood levels of creatinine and hemoglobin A1c (HbA1c), central macular thickness (CMT; measured with optical coherence tomography), mean blur rate (MBR; measured with laser speckle flowgraphy), and ultrasound-measured carotid IMT.Results. Diabetes duration, IMT, and CMT were significantly higher in the mild NPDR patients than the NDR patients (P=0.004,P=0.004, andP=0.003, respectively), while conversely, MBR in the overall optic nerve head (MBR-A) was lower in the mild NPDR patients. Furthermore, a logistic regression analysis showed that diabetes duration (OR, 1.11;P=0.006), diastolic blood pressure (OR, 0.93;P=0.025), heart rate (OR, 1.07;P=0.004), IMT (OR, 8.65;P=0.005), and CMT (OR, 1.03;P=0.007) were independent contributing factors to mild NPDR. Spearman’s rank correlation test also showed that IMT was negatively correlated with MBR-A (P=0.011).Conclusions. Increased IMT showed a close association with ocular ischemia in patients with type-2 diabetes and contributed to the presence of mild NPDR. These findings suggest that IMT may be an early biomarker of mild NPDR.
The Impact ofLactobacillus plantarumon the Gut Microbiota of Mice with DSS-Induced Colitis
Authors: Zhang Fei , Li Yue , Wang Xiliang , Wang Shengping , Bi Dingren
Published: February 2019

The pathogenesis of inflammatory bowel disease (IBD) is due in part to a loss of equilibrium among the gut microbiota, epithelial cells, and resident immune cells. The gut microbiota contains a large proportion of probiotic commensalLactobacillusspecies; some natural microbiota and probiotics confer protection against IBD. In this study, mice with colitis triggered by dextran sodium sulphate (DSS) were givenLactobacillus plantarumorally. We assessed the damage caused by DSS and the therapeutic activity ofL. plantarum. The colitis triggered by DSS was less severe in the mice that received theL. plantarumtreatment, which also diversified the microbe species in the colon, enhanced the ratio of Firmicutes to Bacteroidetes, and diminished the relative abundance ofLactobacillus. The taxonomic units of greatest diversity in the DSS andL. plantarumgroups were identified using a linear discriminant and effect size (LEfSe) analysis.Aliihoefleawas established to be the genus of bacteria that was affected in theL. plantarumgroup most extensively. In conclusion, gut health was promoted byL. plantarum, as it diversified the microbes in the colon and restricted the activity of pathogenic bacteria in the intestine. Moreover, according to the LEfSe analysis, the DSS group was impacted more significantly by gut microorganisms than theL. plantarumgroup, suggesting thatL. plantarumimproved the stability of the intestinal tract.
Induced and Evoked Properties of Vibrotactile Adaptation in the Primary Somatosensory Cortex
Authors: Puts Nicolaas A. J. , Edden Richard A. E. , Muthukumaraswamy Suresh , Singh Krish D. , McGonigle David J.
Published: February 2019

Prolonged exposure to afferent stimulation (“adaptation”) can cause profound short-term changes in the responsiveness of cortical sensory neurons. While several models have been proposed that link adaptation to single-neuron dynamics, including GABAergic inhibition, the process is currently imperfectly understood at the whole-brain level in humans. Here, we used magnetoencephalography (MEG) to examine the neurophysiological correlates of adaptation within SI in humans. In one condition, a 25 Hz adapting stimulus (5 s) was followed by a 1 s 25 Hz probe (“same”), and in a second condition, the adapting stimulus was followed by a 1 s 180 Hz probe (“different”). We hypothesized that changes in the mu-beta activity band (reflecting GABAergic processing) would be modulated differently between the “same” and “different” probe stimuli. We show that the primary somatosensory (SI) mu-beta response to the “same” probe is significantly reduced (p=0.014) compared to the adapting stimulus, whereas the mu-beta response to the “different” probe is not (p=n.s.). This reduction may reflect sharpening of the spatiotemporal pattern of activity after adaptation. The stimulus onset mu-beta response did not differ between a 25 Hz adapting stimulus and a 180 Hz probe, suggesting that the mu-beta response is independent of stimulus frequency. Furthermore, we show a sustained evoked and induced desynchronization for the duration of the adapting stimulus, consistent with invasive studies. Our findings are important in understanding the neurophysiology underlying short-term and stimulus-induced plasticity in the human brain and shows that the brain response to tactile stimulation is altered after only brief stimulation.
Intrauterine Transfusion Complicated by Umbilical Artery Thrombosis
Authors: Donepudi Roopali V. , Moise Kenneth J.
Published: February 2019

Background. Fetal anemia results from several conditions; however intrauterine transfusion (IUT) remains the treatment for severe cases. The complications of this procedure are rare and yet can result in preterm delivery or fetal death. Case. 31 y/o G3P2002 with Rh alloimmunization underwent IUT from 19 to 35 weeks. Umbilical artery thrombosis was noted after her 5th IUT. Further transfusions were performed without any complications and she delivered a full term male infant with APGARS of 8 and 9 at 1 and 5 minutes, respectively. Conclusion. The complication of umbilical artery thrombosis is unusual and the optimal management is unclear. We report such a case and propose that the presence of Hyrtl’s anastomosis near the placental cord insertion may explain the reassuring fetal status throughout the pregnancy.
Bifurcation Analysis of Composite Laminated Piezoelectric Rectangular Plate Structure in the Case of 1:2 Internal Resonance
Authors: Guo Y. H. , Zhang W.
Published: February 2019

In this paper, the authors study the bifurcation problems of the composite laminated piezoelectric rectangular plate structure with three bifurcation parameters by singularity theory in the case of 1:2 internal resonance. The sign function is employed to the universal unfolding of bifurcation equations in this system. The proposed approach can ensure the nondegenerate conditions of the universal unfolding of bifurcation equations in this system to be satisfied. The study presents that the proposed system with three bifurcation parameters is a high codimensional bifurcation problem with codimension 4, and 6 forms of universal unfolding are given. Numerical results show that the whole parametric plane can be divided into several persistent regions by the transition set, and the bifurcation diagrams in different persistent regions are obtained.
Antilisterial Activity of Polypropylene Film Coated with Chitosan with Propolis and/or Bee Pollen in Food Models
Authors: Skowron Krzysztof , Kwiecińska-Piróg Joanna , Grudlewska Katarzyna , Gryń Grzegorz , Wiktorczyk Natalia , Balcerek Maciej , Załuski Daniel , Wałecka-Zacharska Ewa , Kruszewski Stefan , Gospodarek-Komkowska Eugenia
Published: February 2019

The aim of the study was to evaluate the effect of propylene film coated with solution of chitosan (CH), ethanolic extracts of propolis (EEP), and bee pollen (EEBP) and its combination on L. monocytogenes number in wrapped salmon, salami, and cheese. Sterile fragments of propylene film were coated with solution containing CH, CH+EEP, CH+EEBP, and CH+EEP+EEBP. The coated film was applied directly after preparation (AP) after 10 days of storage from preparation (AS). L. monocytogenes strains isolated from cheese, salmon, and salami were transferred on adequate food type. ATCC 19111 reference strain was placed on all examined slices. Contaminated slices were wrapped in the coated film. The film adhered strictly to the slices surface and was left for 0, 1, 6, 12, and 24 hours. Antilisterial activity of AP film was additionally assessed during 15-day storage of products wrapped in the coated film. In conclusion, the chitosan-coated film exhibited antibacterial activity. Incorporation of EPP and EEBP enhanced this activity. The antilisterial activity depended on the type and concentration of solutions, the types of food, and the origin of strains. This study proved that the time that passed since the use of coated film for packing food was of great importance.
Prescribing Trend of Antirheumatic Drugs in Taiwan and Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study
Authors: Lee Chien-Ying , Tai Chih-Jaan , Tsai Ya-Fang , Kuan Yu-Hsiang , Lee Chiu-Hsiang , Huang Kuang-Hua
Published: February 2019

We aimed to investigate the prescribing trend of antirheumatic drugs and assess the risk of cardiovascular disease in patients with rheumatoid arthritis in Taiwan. This study was a retrospective cohort study, conducted based on the Taiwan National Health Insurance Research Database. The study subjects were 15,366 new rheumatoid arthritis patients from 2003 to 2010. To avoid selection bias, we applied propensity score matching to obtain general patients, as the control group. Cox proportional hazard model was used to evaluate the risk of cardiovascular disease in rheumatoid arthritis patients. The most common prescriptions of rheumatoid arthritis were nonsteroidal anti-inflammatory drugs. After controlling for related variables, rheumatoid arthritis patients had a higher risk of cardiovascular disease than general patients (adjusted hazard ratio [aHR] = 1.31; 95% confidence interval [CI]: 1.23-1.39). Age was the most significantly associated risk factor with the cardiovascular disease. Other observed risk factors for cardiovascular disease included hypertension (aHR = 1.57, 95% CI: 1.48-1.65), diabetes mellitus (aHR = 1.47, 95% CI: 1.38-1.57), and chronic kidney disease (aHR = 1.48, 95% CI: 1.31-1.66). Patients with rheumatoid arthritis indeed had a higher risk of incident cardiovascular diseases. Besides, age, hypertension, diabetes mellitus, and chronic kidney disease were also associated with a higher risk of cardiovascular disease.
Production Optimization of an Active β-Galactosidase of Bifidobacterium animalis in Heterologous Expression Systems
Authors: Xu Xinxin , Fan Xiaohu , Fan Chao , Qin Xing , Liu Bo , Nie Chunming , Sun Ning , Yao Qingzhi , Zhang Yuhong , Zhang Wei
Published: February 2019

β-Galactosidase (E.C.3.2.1.23) catalyzes the hydrolysis of lactose into glucose and galactose and the synthesis of galacto-oligosaccharides as well. The β-galactosidases from bacteria, especially lactobacilli, and yeast have neutral pH and are much more likely to be developed as food additives. However, the challenges of cumbersome purification, product toxicity, and low yield in protein production have limited the commercialization of many excellent candidates. In this study, we identified a β-galactosidase gene (bg42-106) in Bifidobacterium animalis ACCC05790 and expressed the gene product in Escherichia coli BL21(DE3) and Pichia pastoris GS115, respectively. The recombinant bG42-106 purified from E. coli cells was found to be optimally active at pH 6.0 and 60°C and had excellent stability over a wide pH range (5.0–8.0) and at high temperature (60°C). The specific activity of bG42-106 reached up to 2351 U/mg under optimal conditions. The galacto-oligosaccharide yield was 24.45 g/L after incubation with bG42-106 at 60°C for 2 h. When recombinant bG42-106 was expressed in Pichia pastoris GS115, it was found in the culture medium but only at a concentration of 1.73 U/ml. To increase its production, three strategies were employed, including codon optimization, disulfide formation, and fusion with a Cherry tag, with Cherry-tag fusion being most effective. The culture medium of P. pastoris that expressed Cherry-tagged bG42-106 contained 24.4 U/mL of β-galactosidase activity, which is 14-fold greater than that produced by culture of P. pastoris harboring wild-type bG42-106.
Epidemiologic Features of Traumatic Fractures in Children and Adolescents: A 9-Year Retrospective Study
Authors: Wang Hongwei , Feng Chencheng , Liu Huan , Liu Jun , Ou Lan , Yu Hailong , Xiang Liangbi
Published: February 2019

Purpose. Fractures are common among all types of paediatric injuries, with differences in incidence over time. Here, we present the epidemiologic features of traumatic fractures in a population of youth ≤ 18 years of age who were admitted to our university-affiliated hospitals from 2002 to 2010. Methods. We retrospectively reviewed 2450 children and adolescents who had traumatic fractures. The data include variables such as age, sex, date of injury, and the mechanism of injury. For the period of 2002-2010, there were 2450 injury events that resulted in at least 1 fracture. Results. Low falls (1042, 42.5%) and upper limb fractures (1068, 43.6%) were the most common aetiologies and fracture sites. With increasing age, the proportion of injuries due to motor vehicle collisions (MVCs) decreased and the injuries due to being hit by others and due to sprains increased. With increasing age, the proportion of craniofacial fractures (CFFs) decreased, and lower limb fractures (LLFs), spinal fractures (SFs), and fractures of ribs and the sternum (RSFs) increased. Over time, the proportion of injuries due to MVCs and mechanical injury decreased. Male patients presented with a significantly higher proportion of injuries due to low falls, being struck by an object, being hit by others, and due to sprains. There were a significantly lower proportion of injuries due to MVCs in female patients. Male patients presented with a significantly higher proportion of ULFs in the ≤6-year-old age group and a significantly lower proportion of LLFs and SFs in the 12-18-year-old age group than did female patients. Conclusions. Low falls and upper limb fractures were the leading cause and fracture sites. To further improve the prevention and treatment of traumatic fractures in children and adolescents, policy makers should pay attention to these characteristics.
Software Development Effort Estimation Using Regression Fuzzy Models
Authors: Nassif Ali Bou , Azzeh Mohammad , Idri Ali , Abran Alain
Published: February 2019

Software effort estimation plays a critical role in project management. Erroneous results may lead to overestimating or underestimating effort, which can have catastrophic consequences on project resources. Machine-learning techniques are increasingly popular in the field. Fuzzy logic models, in particular, are widely used to deal with imprecise and inaccurate data. The main goal of this research was to design and compare three different fuzzy logic models for predicting software estimation effort: Mamdani, Sugeno with constant output, and Sugeno with linear output. To assist in the design of the fuzzy logic models, we conducted regression analysis, an approach we call “regression fuzzy logic.” State-of-the-art and unbiased performance evaluation criteria such as standardized accuracy, effect size, and mean balanced relative error were used to evaluate the models, as well as statistical tests. Models were trained and tested using industrial projects from the International Software Benchmarking Standards Group (ISBSG) dataset. Results showed that data heteroscedasticity affected model performance. Fuzzy logic models were found to be very sensitive to outliers. We concluded that when regression analysis was used to design the model, the Sugeno fuzzy inference system with linear output outperformed the other models.