bluuebunny/crossref_metadata_2025 huggingface dataset:
NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications
Authors: Targher Giovanni , Byrne Christopher D , Tilg Herbert
Published: April 2020

Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.
Acthar Gel (repository corticotropin injection) for persistently active SLE: study design and baseline characteristics from a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Askanase Anca D , Zhao Enxu , Zhu Julie , Connolly-Strong Erin , Furie Richard A
Published: April 2020

Objective

SLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid use.

Methods

Efficacy will be evaluated using the SLE Responder Index-4 (SRI-4), SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) and Physician’s Global Assessment (PGA). The primary efficacy endpoint will be the proportion of SRI-4 responders at week 16. Secondary and exploratory endpoints will include changes in disease activity scores over time, prednisone dose and biomarkers of inflammation and bone turnover. The safety and tolerability profile of RCI will also be evaluated through adverse event profiles, physical examination, clinical laboratory tests and serum cortisol levels.

Results

Target enrolment for this global study is 270 patients, and as of 15 November 2019, the modified intent-to-treat population included 169 patients. The study cohort had 91.7% women, had a mean age of 39.7 years, mean SLEDAI-2K total score of 9.9, mean BILAG-2004 total score of 18.1, mean PGA of 59.7 and mean prednisone or equivalent daily dose of 11.1 mg. A total of 79.3% and 64.5% of patients were receiving concomitant antimalarial or immunosuppressive therapy, respectively.

Conclusions

Data from this study will provide valuable insights into the therapeutic role of RCI in refractory SLE, as well as important information regarding its safety profile.
Exploring the acceptability of implantable defibrillators in patients with cardiac dystrophinopathy and carers
Authors: Hiermeier Ursula M , Baker Christine , Bourke John P
Published: April 2020

Objective

Unlike for patients with other forms of cardiomyopathies, those with severe ventricular dysfunction due to Duchenne muscular dystrophy (DMD) are not offered implantable cardioverter-defibrillator (ICD) therapy routinely. This prospective study aimed to determine the views of DMD-patients and their carers about discussing sudden death risk and their acceptance of ICDs.

Design and setting

Adults with DMD (n=9) and parents/carers (n=9) participated in audio-recorded, 60–90 min focus group sessions (patients 2; parents/carers 2) conducted through either a face-to-face session at a neutral venue or a videoconference. Sessions were facilitated by a clinical psychologist, experienced in conducting focus group research. All participants understood the rationale for the study and the nature of ICD therapy. The same predefined themes were explored with each group. Recordings were transcribed, analysed thematically by two researchers, working independently and then agreed. Differences in responses between patient and carer groups were also studied and compared. Participants all provided informed written consent and the study had ethical approval.

Results

Three main themes emerged: (1) access to/quality of information provided by professionals and patient engagement with them; (2) decision-making about ICDs; (3) individuals’ own ‘lived experience’ of DMD.

Conclusions

The main findings were: (1) patients with DMD want to have their risk of sudden arrhythmic death discussed, when relevant and (2) if ICD therapy were established as beneficial, they would welcome an individualised discussion about its appropriateness for them.
Initiation of any tobacco and five tobacco products across 3 years among youth, young adults and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Stanton Cassandra A , Sharma Eva , Seaman Elizabeth L , Kasza Karin A , Edwards Kathryn C , Halenar Michael J , Taylor Kristie A , Day Hannah , Anic Gabriella , Hull Lynn C , Bansal-Travers Maansi , Limpert Jean , Gardner Lisa D , Hammad Hoda T , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew
Published: April 2020

Objective

This study reports weighted cross-sectional prevalence of never use of tobacco, and longitudinal past 12-month (P12M), past 30-day (P30D) and frequent P30D any tobacco or specific tobacco product initiation across three 1-year waves. Longitudinal three-wave pathways are examined to outline pathways of exclusive and polytobacco initiation, as well as pathways of new initiators of electronic nicotine delivery systems (ENDS) or cigarettes.

Design

Data were drawn from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, N = 11 046; young adults, N = 6478; adults 25+, N = 17 188) were included in longitudinal analyses.

Results

Across the three age groups, weighted cross-sectional analyses revealed never any tobacco use decreased each year from 2013 to 2016, reflecting overall increases in tobacco initiation in the population during this time. Compared with cigarettes, cigars, hookah and smokeless tobacco, ENDS had the highest proportion of P12M initiation from Wave 1 to Wave 3 (W3) for each age group. Among youth Wave 2 P30D initiators of exclusive ENDS or cigarettes, the most common W3 outcome was not using any tobacco (ENDS: 59.0% (95% CI 48.4 to 68.8); cigarettes: 40.3% (95% CI 28.7 to 53.1)).

Conclusions

Initiation rates of ENDS among youth and young adults have increased the number of ever tobacco users in the US prevention strategies across the spectrum of tobacco products which can address youth initiation of tobacco products.
Longitudinal transitions of exclusive and polytobacco electronic nicotine delivery systems (ENDS) use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Stanton Cassandra A , Sharma Eva , Edwards Kathryn C , Halenar Michael J , Taylor Kristie A , Kasza Karin A , Day Hannah , Anic Gabriella , Gardner Lisa D , Hammad Hoda T , Bansal-Travers Maansi , Limpert Jean , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew
Published: April 2020

Objective

Electronic nicotine delivery systems (ENDS; including e-cigarettes) are rapidly evolving in the US marketplace. This study reports cross-sectional prevalence and longitudinal pathways of ENDS use across 3 years, among US youth (12–17 years), young adults (18–24 years) and adults 25+ (25 years and older).

Design

Data were from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses.

Results

Weighted cross-sectional ever use of ENDS increased at each wave. Across all three waves, young adults had the highest percentages of past 12-month, past 30-day (P30D) and daily P30D ENDS use compared with youth and adults 25+. Only about a quarter of users had persistent P30D ENDS use at each wave. Most ENDS users were polytobacco users. Exclusive Wave 1 ENDS users had a higher proportion of subsequent discontinued any tobacco use compared with polytobacco ENDS users who also used cigarettes.

Conclusions

ENDS use is most common among young adults compared with youth and adults 25+. However, continued use of ENDS over 2 years is not common for any age group. Health education efforts to reduce the appeal and availability of ENDS products might focus on reducing ENDS experimentation, and on reaching the smaller subgroups of daily ENDS users to better understand their reasons for use.
Longitudinal pathways of exclusive and polytobacco cigar use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Edwards Kathryn C , Sharma Eva , Halenar Michael J , Taylor Kristie A , Kasza Karin A , Day Hannah , Hammad Hoda T , Anic Gabriella , Bansal-Travers Maansi , Limpert Jean , Gardner Lisa D , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew , Stanton Cassandra A
Published: April 2020

Objective

The goal of this study is to examine the cross-sectional prevalence of use and 3-year longitudinal pathways of cigar use in US youth (12-17 years), young adults (18-24 years), and adults 25+ (25 years or older).

Design

Data were drawn from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses.

Results

Weighted cross-sectional prevalence of past 30-day (P30D) use was stable for adults 25+ (~6%), but decreased in youth (Wave 1 (W1) to Wave 3 (W3)=2.5% to 1.2%) and young adults (W1 to W3=15.7% to 14.0%). Among W1 P30D cigar users, over 50% discontinued cigar use (irrespective of other tobacco use) by Wave 2 (W2) or W3. Across age groups, over 70% of W1 P30D cigar users also indicated P30D use of another tobacco product, predominantly cigar polytobacco use with cigarettes. Discontinuing all tobacco use by W2 or W3 was greater in adult exclusive P30D cigar users compared with polytobacco cigar users.

Conclusions

Although the majority of P30D cigar users discontinued use by W3, adult polytobacco users of cigars were less likely to discontinue all tobacco use than were exclusive cigar users. Tracking patterns of cigar use will allow further assessment of the population health impact of cigars.
Longitudinal pathways of exclusive and polytobacco cigarette use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Taylor Kristie A , Sharma Eva , Edwards Kathryn C , Halenar Michael J , Kissin Wendy , Kasza Karin A , Day Hannah , Anic Gabriella , Gardner Lisa D , Hammad Hoda T , Hull Lynn C , Bansal-Travers Maansi , Limpert Jean , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew , Stanton Cassandra
Published: April 2020

Objective

Cigarettes are the most harmful and most prevalent tobacco product in the USA. This study examines cross-sectional prevalence and longitudinal pathways of cigarette use among US youth (12–17 years), young adults (18–24 years) and adults 25+ (25 years and older).

Design

Data were drawn from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US adults and youth. Respondents with data at all three waves (youth, N=11 046; young adults, N=6478; adults 25+, N=17 188) were included in longitudinal analyses.

Results

Among Wave 1 (W1) any past 30-day (P30D) cigarette users, more than 60%, persistently used cigarettes across three waves in all age groups. Exclusive cigarette use was more common among adult 25+ W1 P30D cigarette users (62.6%), while cigarette polytobacco use was more common among youth (57.1%) and young adults (65.2%). Persistent exclusive cigarette use was the most common pathway among adults 25+ and young adults; transitioning from exclusive cigarette use to cigarette polytobacco use was most common among youth W1 exclusive cigarette users. For W1 youth and young adult cigarette polytobacco users, the most common pattern of use was persistent cigarette polytobacco use.

Conclusions

Cigarette use remains persistent across time, regardless of age, with most W1 P30D smokers continuing to smoke at all three waves. Policy efforts need to continue focusing on cigarettes, in addition to products such as electronic nicotine delivery systems that are becoming more prevalent.
Asymmetric input motion for accumulation of lateral ground deformation in laminar container shake table testing
Authors: Zayed Muhammad , Ebeido Ahmed , Prabhakaran Athul , Qiu Zhijian , Elgamal Ahmed
Published: April 2020

Due to seismic response, accumulation of permanent ground deformation (lateral spreading) is an important mechanism of much practical significance. Such deformations typically occur near a ground slope, behind retaining structures such as sheet-pile and quay walls, and in mildly sloping ground. In conducting a shake table test, the generation of permanent deformations further elucidates the underlying mechanisms and allows for related ground–foundation–structure response insights. In this paper, an approach for development of accumulated ground deformations is presented, in which asymmetric inertial loading results in a biased dynamic one-dimensional shear state of stress. As such, the proposed approach allows for further insights into the soil cyclic response and pore pressure build-up, with deformations accumulating in a preferred direction. To permit a virtually unlimited number of such loading cycles, focus is placed on motions that do not cause the shake-table actuator to accumulate displacement, in view of its possible limited stroke. Using this approach, representative experimental response is outlined and discussed. This experimental response can be used for calibration of numerical models to emulate the observed permanent strain accumulation profile and associated mechanisms. In addition to liquefaction-induced lateral spreading, this asymmetric shaking approach might be beneficial for a wide class of earthquake engineering shake table testing applications.
The effect of charge transfer on the transport properties of Si2Li clusters: a first-principles study
Authors: Wang Qingling , Liu Wenhua , Zhou Qinghua , Liang Yan , Hu Wei , Wan Haiqing
Published: April 2020

The transport properties of two different Si2Li clusters adsorption structures (bridge-site type and apex-site type) between two semi-infinite Au(100)-3 × 3 electrodes have been studied using first principles based on density functional theory and non-equilibrium Green's function in this paper. The I–V curves of both systems are linear and demonstrate the properties of metal resistance. The bridge-site type displays better electron transport capacity due to more transferring charge between the cluster and electrodes. The conductance change of the two systems becomes completely different due to the drift of the energy level under bias, which is no longer dependent on the transfer of charge.
Conformal evolution of phantom dominated final stages of the universe in higher dimensions
Authors: Natarajan S. , Chandramohan R.
Published: April 2020

Friedmann solutions and higher-dimensional 5D Kaluza–Klein solutions using mathematical packages such as Sagemath and Cadabra are calculated. A modified Friedmann equation powered by loop quantum gravity in higher dimensions is calculated in this work. Loop quantization in extra-dimensional space is predicted. Modified equation of state for non-interacting dark matter and dark energy are calculated. It has been predicted that the higher curvature due to phantom density would be a local kind of quantized curvature. The modified Friedmann solutions with Kaluza–Klein interpretation are found. To achieve a conformal exit, the non-interacting solutions are discussed in this work. The obtained results are compared with the ΛCDM and quintessence models. The results support conformal cyclic cosmology, which predicts the conformal evolution of the universe without facing any singularity as the result of topological effects.
New solitary waves for the Klein–Gordon–Zakharov equations
Authors: Nestor Savaissou , Houwe Alphonse , Rezazadeh Hadi , Bekir Ahmet , Betchewe Gambo , Doka Serge Y.
Published: April 2020

This paper studies new solitary waves for the Klein–Gordon–Zakharov equations. The obtained results are diverse and some specific ones emerge as dark, bright and bell-shape. The two integration schemes lead to obtaining waves which propagate without deformation as illustrated in graphical representations. Our obtained results are more specific compared to those obtained by Refs. 8 and 31 [C. H. Zhao and Z. M. Sheng, Acta Phys. Sin. 53 (2004) 29; S. Yakada, B. Depelair, G. Betchewe and S. Y. Doka, Optik 197 (2019) 163108].
Petrogenesis of Siluro-Devonian rhyolites of the Tobique Group in the northwestern Appalachians (northern New Brunswick, Canada): tectonic implications for the accretion history of peri-Gondwanan terranes along the Laurentian margin
Authors: Dostal Jaroslav , Wilson Reginald A. , Jutras Pierre
Published: April 2020

Uppermost Silurian–Lower Devonian felsic rocks in the bimodal volcanic suite of the Tobique Group in the northwestern mainland Appalachians (northern New Brunswick, Canada) form part of an overstep sequence deposited across the accreted vestiges of Iapetus Ocean on composite Laurentia. Whereas the mafic rocks of the bimodal volcanic suite are continental tholeiites, the felsic rocks are peraluminous and possess geochemical characteristics of A2-type granites emplaced in post-collisional extensional settings. The major and trace element compositions of the felsic rocks indicate that they were generated by dehydration melting of late Precambrian granitoid rocks triggered by heat derived from the rising mafic magma. Unlike the basalts, which have positive
ε
Nd
(
t
) values, the felsic rocks have values close to chondrites (−1.6 to +1.1), which is consistent with derivation from a crustal source. The rapid transition from compressional to extensional magmatism in latest Silurian–Early Devonian times in this part of Ganderia is probably due to Late Silurian Ganderia–Laurentia collision followed by slab breakoff. Based on Sm–Nd isotopic characteristics in their respective igneous rocks, both Ganderia and Avalonia are underlain by similar Neoproterozoic lower–middle crust and subcontinental lithospheric mantle.
Visual Search: How Do We Find What We Are Looking For?
Authors: Wolfe Jeremy M.
Published: April 2020

In visual search tasks, observers look for targets among distractors. In the lab, this often takes the form of multiple searches for a simple shape that may or may not be present among other items scattered at random on a computer screen (e.g., Find a red T among other letters that are either black or red.). In the real world, observers may search for multiple classes of target in complex scenes that occur only once (e.g., As I emerge from the subway, can I find lunch, my friend, and a street sign in the scene before me?). This article reviews work on how search is guided intelligently. I ask how serial and parallel processes collaborate in visual search, describe the distinction between search templates in working memory and target templates in long-term memory, and consider how searches are terminated.
Topographic Variations in Retinal Encoding of Visual Space
Authors: Heukamp Alina Sophie , Warwick Rebekah Anne , Rivlin-Etzion Michal
Published: April 2020

A retina completely devoid of topographic variations would be homogenous, encoding any given feature uniformly across the visual field. In a naive view, such homogeneity would appear advantageous. However, it is now clear that retinal topographic variations exist across mammalian species in a variety of forms and patterns. We briefly review some of the more established topographic variations in retinas of different mammalian species and focus on the recent discovery that cells belonging to a single neuronal subtype may exhibit distinct topographic variations in distribution, morphology, and even function. We concentrate on the mouse retina—originally viewed as homogenous—in which genetic labeling of distinct neuronal subtypes and other advanced techniques have revealed unexpected anatomical and physiological topographic variations. Notably, different subtypes reveal different patterns of nonuniformity, which may even be opposite or orthogonal to one another. These topographic variations in the encoding of visual space should be considered when studying visual processing in the retina and beyond.
The cellular and molecular basis of in vivo synaptic plasticity in rodents
Authors: Cheyne Juliette E. , Montgomery Johanna M.
Published: April 2020

Plasticity within the neuronal networks of the brain underlies the ability to learn and retain new information. The initial discovery of synaptic plasticity occurred by measuring synaptic strength in vivo, applying external stimulation and observing an increase in synaptic strength termed long-term potentiation (LTP). Many of the molecular pathways involved in LTP and other forms of synaptic plasticity were subsequently uncovered in vitro. Over the last few decades, technological advances in recording and imaging in live animals have seen many of these molecular mechanisms confirmed in vivo, including structural changes both pre- and postsynaptically, changes in synaptic strength, and changes in neuronal excitability. A well-studied aspect of neuronal plasticity is the capacity of the brain to adapt to its environment, gained by comparing the brains of deprived and experienced animals in vivo, and in direct response to sensory stimuli. Multiple in vivo studies have also strongly linked plastic changes to memory by interfering with the expression of plasticity and by manipulating memory engrams. Plasticity in vivo also occurs in the absence of any form of external stimulation, i.e., during spontaneous network activity occurring with brain development. However, there is still much to learn about how plasticity is induced during natural learning and how this is altered in neurological disorders.
Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury
Authors: LaRivière W. B. , Liao S. , McMurtry S. A. , Oshima K. , Han X. , Zhang F. , Yan S. , Haeger S. M. , Ransom M. , Bastarache J. A. , Linhardt R. J. , Schmidt E. P. , Yang Y.
Published: April 2020

The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Delayed inhibition of metalloproteinases, beginning 7 days after bleomycin using the nonspecific MMP inhibitor doxycycline, attenuated heparan sulfate shedding and improved lung function, suggesting that heparan sulfate shedding may impair lung recovery. While we also observed an increase in air space heparanase activity after bleomycin, pharmacological and transgenic inhibition of heparanase in vivo failed to attenuate heparan sulfate shedding or protect against bleomycin-induced lung injury. However, experimental augmentation of airway heparanase activity significantly worsened post-bleomycin outcomes, confirming the importance of epithelial glycocalyx integrity to lung recovery. We hypothesized that MMP-associated heparan sulfate shedding contributed to delayed lung recovery, in part, by the release of large, highly sulfated fragments that sequestered lung-reparative growth factors such as hepatocyte growth factor. In vitro, heparan sulfate bound hepatocyte growth factor and attenuated growth factor signaling, suggesting that heparan sulfate shed into the air space after injury may directly impair lung repair. Accordingly, administration of exogenous heparan sulfate to mice after bleomycin injury increased the likelihood of death due to severe lung dysfunction. Together, our findings demonstrate that alveolar epithelial heparan sulfate shedding impedes lung recovery after bleomycin.
Interleukin-17 signaling mediates cytolytic natural killer cell activation in response to placental ischemia
Authors: Travis Olivia K. , White Dakota , Baik Cedar , Giachelli Chelsea , Thompson Willie , Stubbs Cassandra , Greer Mallory , Lemon James P. , Williams Jan Michael , Cornelius Denise C.
Published: April 2020

T-helper (TH)17s, IL-17, and cytolytic natural killer cells (cNKs) are increased in preeclampsia and contribute to the hypertension, inflammation, and fetal growth restriction that occurs in response to placental ischemia in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. As IL-17 stimulates NK cytotoxicity in vitro, we tested the hypothesis that IL-17 inhibition in RUPP rats would decrease cNK activation as a mechanism to improve maternal and fetal outcomes. On gestation day (GD) 14, rats undergoing RUPP received a miniosmotic pump infusing IL-17RC (100 pg/day), a soluble IL-17 receptor (RUPP + IL-17RC). On GD19, mean arterial pressure (MAP) was measured in normal pregnant (NP), RUPP, and RUPP + IL-17RC rats ( n = 10–12/group), animals were euthanized, and blood and tissues were collected for analysis. MAP was 30% higher in RUPP compared with NP ( P < 0.0001) and was 12% lower in RUPP + IL-17RC ( P = 0.0007 vs. RUPP). Placental cytolytic NK cells were 132% higher in RUPP than in NP ( P = 0.04 vs. NP) and were normalized in RUPP + IL-17RC ( P = 0.03 vs. RUPP). Placental levels of TNF-α, a cNK-secreted cytokine, and macrophage inflammatory protein-3α (MIP-3α), a cNK chemokine, were higher in RUPP vs. NP and lower after IL-17 blockade. Placental VEGF was lower in RUPP vs. NP and was normalized in RUPP + IL-17RC. In vitro cytolytic activity of RUPP placental NKs was higher compared with NP and was blunted in RUPP + IL-17RC NKs. Finally, both fetal weight and placental weight were lower in RUPP compared with NP, and were improved in RUPP + IL-17RC. These data identify IL-17 as a mediator of cNK activation in response to placental ischemia during pregnancy.
Motor style at rest and during locomotion in humans
Authors: Mantilla Juan , Wang Danping , Bargiotas Ioannis , Wang Junhong , Cao Jiuwen , Oudre Laurent , Vidal Pierre-Paul
Published: April 2020

During human locomotion, motor control can be conveniently decomposed into a static and dynamic components. Variable dynamics were observed at both the intra- and interindividual levels during locomotion. Variability increased following a head-to-toe gradient. Finally, our results support the view that postural and motor control are subserved by different neuronal networks in the frontal, sagittal, and transversal planes.
Rapid adaptation to elevated extracellular potassium in the pyloric circuit of the crab, Cancer borealis
Authors: He Lily S. , Rue Mara C.P. , Morozova Ekaterina O. , Powell Daniel J. , James Eric J. , Kar Manaswini , Marder Eve
Published: April 2020

Solutions with elevated extracellular potassium are commonly used as a depolarizing stimulus. We studied the effects of high potassium concentration ([K+]) on the pyloric circuit of the crab stomatogastric ganglion. A 2.5-fold increase in extracellular [K+] caused a transient loss of activity that was not due to depolarization block, followed by a rapid increase in excitability and recovery of spiking within minutes. This suggests that changing extracellular potassium can have complex and nonstationary effects on neuronal circuits.
Abnormal development of auditory responses in the inferior colliculus of a mouse model of Fragile X Syndrome
Authors: Nguyen Anna O. , Binder Devin K. , Ethell Iryna M. , Razak Khaleel A.
Published: April 2020

Autism spectrum disorders (ASD) are commonly associated with sensory sensitivity issues, but the underlying mechanisms are unclear. This study presents novel evidence for neural correlates of auditory hypersensitivity in the developing inferior colliculus (IC) in the Fmr1 knockout (KO) mouse, a mouse model of Fragile X Syndrome (FXS), a leading genetic cause of ASD. Responses begin to show genotype differences between postnatal days 14 and 21, suggesting an early developmental treatment window.
Absolute Neutrophil Count and Mean Platelet Volume in the Blood as Biomarkers to Detect Lung Cancer
Authors: Zhu Xuming , Chen Yan , Cui Yubao
Published: April 2020

Objective. Inflammation plays an extremely considerable role in the development and progression of malignancies. Absolute neutrophil count (ANC) and mean platelet volume (MPV) in blood are associated with various inflammatory conditions and resulted in independent prognostic factors for lung cancer. However, whether ANC and MPV can be diagnostic markers for lung cancer remains unknown. This retrospective study investigated the roles of ANC and MPV, either alone or combined, in diagnosing lung cancer. Methods. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People’s Hospital Affiliated with Nanjing Medical University. The Mann–Whitney U-test was performed to compare differences between lung cancer patients and healthy individuals. Spearman’s correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. Results. 209 patients diagnosed with lung cancer and 236 healthy subjects were enrolled in this study. Levels of ANC and MPV increased in lung cancer patients compared with healthy individuals (P<0.001). ANC had statistically significant negative weak correlation with albumin concentrations (r=‐0.154, P=0.026), and MPV had statistically significant negative weak correlation with total protein concentrations (r=‐0.153, P=0.027) in lung cancer patients. ANC and neutrophil-to-lymphocyte ratio had statistically significant positive correlation in both lung cancer patients (r=0.756, P<0.001) and healthy subjects (r=0.639, P<0.001). MPV and platelet-to-lymphocyte ratio had statistically significant negative weak correlation in both lung cancer patients (r=‐0.242, P<0.001) and healthy subjects (r=‐0.325, P<0.001). ANC had sensitivity (SEN) and specificity (SPE) of 0.512 and 0.809, respectively, and the area under the curve (AUC) with 95% confidence interval (95% CI) was 0.656 (0.603-0.710). SEN and SPE of MPV were 0.928 and 0.708, respectively, and the AUC (95% CI) was 0.913 (0.889-0.938). When ANC and MPV were combined, SEN and SPE became 0.842 and 0.835, respectively, and the AUC (95% CI) became 0.919 (0.895-0.943). Conclusions. Compared with ANC or MPV alone, the combination of ANC and MPV can improve diagnostic ability to distinguish lung cancer patients from healthy subjects.
Synthesis, Characterization, and In Vitro and In Vivo Evaluations of Cellulose Hydrogels Enriched with Larrea tridentata for Regenerative Applications
Authors: Tovar-Carrillo Karla Lizette , Saucedo-Acuña Rosa A. , Ríos-Arana Judith , Tamayo Genaro , Guzmán-Gastellum Dalia Abril , Díaz-Torres Beatriz A. , Nava-Martínez Salvador David , Espinosa-Cristóbal León Francisco , Cuevas-González Juan Carlos
Published: April 2020

Introduction. Tissue engineering is an elementary necessity for several applications in the biomedical field through the use of several biopolymers derived from plants. Larrea tridentata (LT) is a very used plant for various medicinal applications with interesting properties; however, its use into cellulose hydrogels for possible regenerative therapeutics is still limited. Cellulose films could be applied in medical field as wound healing, scaffold for connective tissue for periodontal applications, and so on. The aim of this study was to evaluate the mechanical properties and in vivo and in vitro biocompatibility of cellulose hydrogels that have been enriched with LT in a rat model. Methods. By in vivo and in vitro assays, the concentration of LT was varied from 1 to 5 wt%, respectively. Hydrogel films were implanted intramuscularly into female Wistar rats, 250 g in weight and aged 2 months, to analyze their cytocompatibility and biocompatibility. Results. No case showed any evidence of inflammation or toxicity. Regarding cell morphology and adhesion, the prepared LT cellulose films had better cytocompatibility values than when polystyrene (PS) dishes were used as the control. In all cases, the results suggest that the addition of LT to the hydrogel films did not affect their cytocompatibility or biocompatibility properties and increases their clinical application due to the reported uses of LT. Conclusions. Cellulose hydrogel films enriched with LT have the potential to be used in the biomedical field acting as regenerative scaffolds.
Knowledge, Awareness, and Health‐Seeking Behaviour regarding Tuberculosis in a Rural District of Khyber Pakhtunkhwa, Pakistan
Authors: Khan Adeela , Shaikh Babar Tasneem , Baig Mirza Amir
Published: April 2020

Background. Pakistan is a country with one of the highest burden of tuberculosis (TB) in the world, and therefore, it is imperative to revisit the design of behaviour change interventions in the program. This study was designed to understand and assess the knowledge, awareness, perceptions, and health‐seeking behaviour of general and specifically TB‐affected population and to determine the presence and level of stigma and discrimination toward TB patients. Methods. A mixed‐method study was conducted in district Haripur of the Khyber Pakhtunkhwa province, comprising a household survey, whereby 526 individuals were interviewed, and five focus group discussions with various subgroups including TB patients and health workers and authorities. Study sought an ethical approval, and data of all respondents was kept confidential. Results. Quantitative results show that women were more knowledgeable on symptomatology and spread of TB, and with rising education, awareness on TB improves. The majority of our respondents had the understanding that it is a curable disease, yet some would avoid TB patients. Most of the respondents (both men and women) knew that one must go to a government facility for treatment. Only one‐third would speak to doctor first, if they suspect TB‐like symptoms. Television was a popular source of information on TB. Qualitative results captured people’s perceptions that TB was related with poverty and was still considered a stigma in the community; hence, patients afflicted feared disclosing the disease. Conclusion. With contextual understanding of communities’ knowledge, attitudes, health‐seeking behaviour, and care‐seeking patterns, it can be concluded that there is a need to increase the awareness about TB symptoms, mode of transmission, prevention, diagnosis and treatment, and destigmatization of the disease through health education.
Diagnostic and Prognostic Values of MANF Expression in Hepatocellular Carcinoma
Authors: He Jingyi , Li Guangbing , Liu Xihan , Ma Liye , Zhang Peng , Zhang Jiayao , Zheng Shunzhen , Wang Jianping , Liu Jun
Published: April 2020

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its prognosis is still poor. Mesencephalic astrocyte‐derived neurotrophic factor (MANF) plays a key role in endoplasmic reticulum stress. ER stress plays a key role in HCC carcinogenesis. To confirm the clinical and prognostic value of MANF in HCC, we investigated the expression level of MANF in HCC as recorded in databases, and the results were verified by experiment. Survival analysis was probed by the Kaplan–Meier method. Cox regression models were used to ascertain the prognostic value of MANF in HCC tissue microarray. The diagnostic value of MANF in HCC was evaluated by receiver operating characteristic curve analysis. Potential correlation between MANF and selected genes was also analyzed. Results showed that MANF was overexpressed in HCC. Patients with high MANF expression levels had a worse prognosis and higher risk of tumor recurrence. Furthermore, the expression level of MANF had good diagnostic power. Correlation analysis revealed potential regulatory networks of MANF in HCC, laying a foundation for further study of the role of MANF in tumorigenesis. In conclusion, MANF was overexpressed in HCC and related to the occurrence and development of HCC. It is a potential diagnostic and prognostic indicator of HCC.
Incremental Instance-Oriented 3D Semantic Mapping via RGB-D Cameras for Unknown Indoor Scene
Authors: Li Wei , Gu Junhua , Chen Benwen , Han Jungong
Published: April 2020

Scene parsing plays a crucial role when accomplishing human-robot interaction tasks. As the “eye” of the robot, RGB-D camera is one of the most important components for collecting multiview images to construct instance-oriented 3D environment semantic maps, especially in unknown indoor scenes. Although there are plenty of studies developing accurate object-level mapping systems with different types of cameras, these methods either process the instance segmentation problem in completed mapping or suffer from a critical real-time issue due to heavy computation processing required. In this paper, we propose a novel method to incrementally build instance-oriented 3D semantic maps directly from images acquired by the RGB-D camera. To ensure an efficient reconstruction of 3D objects with semantic and instance IDs, the input RGB images are operated by a real-time deep-learned object detector. To obtain accurate point cloud cluster, we adopt the Gaussian mixture model as an optimizer after processing 2D to 3D projection. Next, we present a data association strategy to update class probabilities across the frames. Finally, a map integration strategy fuses information about their 3D shapes, locations, and instance IDs in a faster way. We evaluate our system on different indoor scenes including offices, bedrooms, and living rooms from the SceneNN dataset, and the results show that our method not only builds the instance-oriented semantic map efficiently but also enhances the accuracy of the individual instance in the scene.
miR-200b/200a/429 Cluster Stimulates Ovarian Cancer Development by Targeting ING5
Authors: Guan Wei , Cui Huiling , Huang Ping , Chun Wan Joo , Lee Jin-Won , Kim Heasung , Zou Hua
Published: April 2020

Ovarian cancer is the second most common gynaecological malignancy, and microRNAs (miRNAs) play important role in the cancer development. Here, we found that the level of miR-200b/200a/429 was significantly increased in serum and tumor tissues of patients with stage-I ovarian cancer. Consistent with these results, we detected increased expression levels of miR-200b/200a/429 in ovarian cancer cell lines compared with the human nontumorigenic ovarian epithelial cell line T80. The overexpression of miR-200b/200a/429 in T80 cells stimulated proliferation and caused their growth in soft agar and tumor formation in nude mice. Furthermore, we determined that miR-200b/200a/429 targets inhibitor of growth family 5 (ING5) and that the overexpression of ING5 can block miR-200b/200a/429-induced T80 cell transformation and tumorigenesis. Our findings suggest that miR-200b/200a/429 may be a useful biomarker for the early detection of ovarian cancer and that miR-200b/200a/429 significantly contributes to ovarian cancer development through ING5.
Macrophage Activities in Myocardial Infarction and Heart Failure
Authors: Duncan Sophia Esi , Gao Shan , Sarhene Michael , Coffie Joel Wake , Linhua Deng , Bao Xingru , Jing Zhang , Li Sheng , Guo Rui , Su Jing , Fan Guanwei
Published: April 2020

Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.
Actual and Predictive Transport Modeling of Fluoride Contamination of the Sfax-Agareb Coastal Aquifer in the Mediterranean Basin
Authors: Melki Samira , Mabrouk El Asmi Amina , Ould Baba Sy Mohamadou , Gueddari Moncef
Published: April 2020

The Tunisian coast is suffering from several active or abandoned polluted sites, suspected to have released high concentrations of various contaminants infiltrating the environment and probably causing groundwater degradation. Within this scope, this study comes to assess and model the Sfax-Agareb aquifer contamination by fluoride released through phosphogypsum leachate percolation. For that, a spatial-temporal monitoring of fluoride contents was achieved for the period between October 2013 and October 2014. Observed data show that hazardous water contamination is occurring especially close to the phosphogypsum leachate collection basins. At this level, groundwater fluoride concentrations may reach up to 29 mg/L. Flow and transport modeling to evaluate fluoride contamination plume expansion in 2030 was achieved using MODFLOW and MT3DMS software packages based on a homogeneous and isotropic aquifer conceptual model. Flow and transport model calibrations were assessed by varying hydraulic conductivity, effective porosity, and dispersivity and then validated through observed data for two reference dates (October 2013 and October 2014). Based on the Tunisian NT 106-002 liquid discharge norms, fluoride contamination front was set at 3 mg/L. Numerical simulation shows that, in 2014, plume contamination by fluoride in the saturated zone extended over 250 m from the contamination source. In 2030, the spatial extent of this contamination will extend over a distance of 900 m towards the sea, following the aquifer flow direction. At the control piezometer, fluoride concentrations will increase from 29 mg/L in 2014 to 86 mg/L in 2030. This study, using numerical modeling, gives new insights for short- and medium-term prediction of eventual fluoride concentrations in the saturated zone of the Sfax-Agareb aquifer.
A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix
Authors: Zhou Mengting , Hu Naihua , Liu Meichen , Deng Ying , He Linfeng , Guo Chaocheng , Zhao Xingtao , Li Yunxia
Published: April 2020

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients’ compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.
A Particle Swarm Optimization Algorithm for Solving Pricing and Lead Time Quotation in a Dual-Channel Supply Chain with Multiple Customer Classes
Authors: Honarvar Mahboobeh , Alimohammadi Ardakani Majid , Modarres Mohammad
Published: April 2020

The combination of traditional retail channel with direct channel adds a new dimension of competition to manufacturers’ distribution system. In this paper, we consider a make-to-order manufacturer with two channels of sale, sale through retailers and online direct sale. The customers are classified into different classes, based on their sensitivity to price and due date. The orders of traditional retail channel customers are fulfilled in the same period of ordering. However, price and due date are quoted to the online customers based on the available capacity as well as the other orders in the pipeline. We develop two different structures of the supply chain: centralized and decentralized dual-channel supply chain which are formulated as bilevel binary nonlinear models. The Particle Swarm Optimization algorithm is also developed to obtain a satisfactory near-optimal solution and compared to a genetic algorithm. Through various numerical analyses, we investigate the effects of the customers’ preference of a direct channel on the model’s variables.