bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of neutrons on charge-changing cross-sections
Authors: Fan G. W. , Zhan Xu
Published: September 2019

The influence of neutrons on charge changing cross-sections ([Formula: see text]) in C isotopes on [Formula: see text]C and proton targets has been investigated in the framework of Glauber model. By comparing the theoretical results and experimental data, it is found out that the influence mainly comes from the projectile neutrons, and the [Formula: see text] has a slight change with the increase of the neutron number. Besides, the calculations also illustrate that the influence gets bigger with the reduction of the incident energy.
On the probability that an automorphism of a group fixes an element of the group
Authors: Goyal Ashish , Kalra Hemant , Gumber Deepak
Published: September 2019

Let [Formula: see text] be a finite group and let [Formula: see text] denote the probability that a randomly chosen element from [Formula: see text] fixes a randomly chosen element from [Formula: see text]. We classify all finite abelian groups [Formula: see text] such that [Formula: see text] in the cases when [Formula: see text] is the smallest prime dividing [Formula: see text], and when [Formula: see text] is any prime. We also compute [Formula: see text] for some classes of finite groups. As a consequence of our results, we deduce that if [Formula: see text] is a finite [Formula: see text]-group having a cyclic maximal subgroup, then [Formula: see text] divides [Formula: see text].
The Nonlocal Strain Gradient Theory for Hygrothermo-Electromagnetic Effects on Buckling, Vibration and Wave Propagation in Piezoelectromagnetic Nanoplates
Authors: Abazid Mohammad Alakel
Published: September 2019

A nonlocal strain gradient theory (NSGT) is utilized to investigate the thermal buckling, free vibration and wave propagation in smart piezoelectromagnetic nanoplates in hygrothermal environments embedded in an elastic substrate. The main advantage of the NSGT over other continuum theories is that it contains both nonlocal parameter and material length scale parameter. The elastic substrate is modeled as Pasternak foundation model. According to the NSGT and the sinusoidal two-variable shear deformation plate theory, the governing equations of motion are derived involving the material parameters and hygrothermo-electromagnetic effects. The present solutions are checked through comparisons with those presented in the literature. Numerical results show the impacts of the nonlocal and gradient parameters, side-to-thickness ratio, hygrothermo-electromagnetic loads and substrate stiffness on the thermal buckling, frequencies and wave propagation in the smart nanoplates.
Application of functional near-infrared spectroscopy in the healthcare industry: A review
Authors: Hong Keum-Shik , Yaqub M. Atif
Published: September 2019

Functional near-infrared spectroscopy (fNIRS), a growing neuroimaging modality, has been utilized over the past few decades to understand the neuronal behavior in the brain. The technique has been used to assess the brain hemodynamics of impaired cohorts as well as able-bodied. Neuroimaging is a critical technique for patients with impaired cognitive or motor behaviors. The portable nature of the fNIRS system is suitable for frequent monitoring of the patients who exhibit impaired brain activity. This study comprehensively reviews brain-impaired patients: The studies involving patient populations and the diseases discussed in more than 10 works are included. Eleven diseases examined in this paper include autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, depressive disorders, anxiety and panic disorder, schizophrenia, mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, stroke, and traumatic brain injury. For each disease, the tasks used for examination, fNIRS variables, and significant findings on the impairment are discussed. The channel configurations and the regions of interest are also outlined. Detecting the occurrence of symptoms at an earlier stage is vital for better rehabilitation and faster recovery. This paper illustrates the usability of fNIRS for early detection of impairment and the usefulness in monitoring the rehabilitation process. Finally, the limitations of the current fNIRS systems (i.e., nonexistence of a standard method and the lack of well-established features for classification) and future research directions are discussed. The authors hope that the findings in this paper would lead to advanced breakthrough discoveries in the fNIRS field in the future.
Rethinking the Combined and Individual Orders of Derivative of States for Differential Recurrent Neural Networks
Authors: Zhuang Naifan , Qi Guo-Jun , Kieu The Duc , Hua Kien A.
Published: September 2019

Due to their special gating schemes, Long Short-Term Memory (LSTM) has shown greater potential to process complex sequential information than the traditional Recurrent Neural Network (RNN). The conventional LSTM, however, fails to take into consideration the impact of salient spatio-temporal dynamics present in the sequential input data. This problem was first addressed by the differential Recurrent Neural Network (dRNN), which uses a differential gating scheme known as Derivative of States (DoS). DoS uses higher orders of internal state derivatives to analyze the change in information gain originated from the salient motions between the successive frames. The weighted combination of several orders of DoS is then used to modulate the gates in dRNN. While each individual order of DoS is good at modeling a certain level of salient spatio-temporal sequences, the sum of all the orders of DoS could distort the detected motion patterns. To address this problem, we propose to control the LSTM gates via individual orders of DoS. To fully utilize the different orders of DoS, we further propose to stack multiple levels of LSTM cells in an increasing order of state derivatives. The proposed model progressively builds up the ability of the LSTM gates to detect salient dynamical patterns in deeper stacked layers modeling higher orders of DoS; thus, the proposed LSTM model is termed deep differential Recurrent Neural Network (
d
2
RNN). The effectiveness of the proposed model is demonstrated on three publicly available human activity datasets: NUS-HGA, Violent-Flows, and UCF101. The proposed model outperforms both LSTM and non-LSTM based state-of-the-art algorithms.
Interactive Technologies Designed for Children with Autism
Authors: Putnam Cynthia , Hanschke Christina , Todd Jennifer , Gemmell Jonathan , Kollia Mia
Published: September 2019

Autism spectrum disorder (ASD) affects many people; the Center for Disease Control and Prevention estimates that 1 in 59 children are currently identified with ASD in the United States. Although it is difficult to generalize about people with ASD due to their heterogeneity, many share an affinity for technologies; as such, numerous academic endeavors and commercial products have focused on the creation of interactive technologies for ASD. In this article, we present findings from 19 interviews and 230 surveys with parents, teachers, and therapists who had children with ASD in their care and had considered or used interactive technologies with those children. We aimed to understand how interactive technologies were used, perceived, desired, and discovered. Findings of use and perception included the following: participants had tried a wide range of commercially available technologies but had very few reported products in common, products were limited to commercial mobile-based apps, and apps were typically perceived positively. In regard to desires, participants hoped for future technologies on diverse platforms (e.g., robots, virtual reality) with more consideration given to personalization, customization, and incorporation of audio and video. Findings about discovery included the following: participants chose technologies in an information-poor environment, and although there are many academic projects aimed at participants’ desires, no participants reported any experience working with researchers. Implications of this study include the need for a recommendation and information sharing system to help people choose and discover appropriate and effective interactive technologies that are a good fit for their child. This work also pointed to a need for such a system to include findings from lab (experimental and usability) studies of commercially available interactive technologies to provide measures of efficacy and usability. Our envisioned system could also potentially help academic researchers with outreach to wider audiences.
Parole Release and Supervision: Critical Drivers of American Prison Policy
Authors: Reitz Kevin R. , Rhine Edward E.
Published: September 2019

Decisions tied to parole release, supervision, and revocation are major determinants of the ebb and flow of prison populations across two-thirds of US states. We argue that parole release, as an institution, has been an underacknowledged force in American incarceration and reincarceration policy and an important contributor to the nation's buildup to mass incarceration. In paroling states, no court or state agency holds greater power than parole boards over time actually served by the majority of offenders sent to prison. We examine the leverage exercised by parole boards through their discretionary release decisions and their powers to sanction violators of parole conditions. We note the state-by-state diversity and complexity associated with parole-release decisions and the absence of successful state systems that might serve as a model for other jurisdictions. We highlight the procedural shortfalls universally associated with parole decision-making. We discuss the long reach of parole supervision and the pains it imposes on those subject to its jurisdiction, including the substantial financial burdens levied on parolees. We then turn to the prospects for parole reform and outline a comprehensive blueprint for improving parole release in America.
Machine Learning for Fluid Mechanics
Authors: Brunton Steven L. , Noack Bernd R. , Koumoutsakos Petros
Published: September 2019

The field of fluid mechanics is rapidly advancing, driven by unprecedented volumes of data from experiments, field measurements, and large-scale simulations at multiple spatiotemporal scales. Machine learning (ML) offers a wealth of techniques to extract information from data that can be translated into knowledge about the underlying fluid mechanics. Moreover, ML algorithms can augment domain knowledge and automate tasks related to flow control and optimization. This article presents an overview of past history, current developments, and emerging opportunities of ML for fluid mechanics. We outline fundamental ML methodologies and discuss their uses for understanding, modeling, optimizing, and controlling fluid flows. The strengths and limitations of these methods are addressed from the perspective of scientific inquiry that considers data as an inherent part of modeling, experiments, and simulations. ML provides a powerful information-processing framework that can augment, and possibly even transform, current lines of fluid mechanics research and industrial applications.
Neurophysiological responses and adaptation following repeated bouts of maximal lengthening contractions in young and older adults
Authors: Škarabot Jakob , Ansdell Paul , Temesi John , Howatson Glyn , Goodall Stuart , Durbaba Rade
Published: September 2019

A bout of maximal lengthening contractions is known to produce muscle damage, but confers protection against subsequent damaging bouts, with both tending to be lower in older adults. Neural factors contribute to this adaptation, but the role of the corticospinal pathway remains unclear. Twelve young (27 ± 5 yr) and 11 older adults (66 ± 4 yr) performed two bouts of 60 maximal lengthening dorsiflexions 2 weeks apart. Neuromuscular responses were measured preexercise, immediately postexercise, and at 24 and 72 h following both bouts. The initial bout resulted in prolonged reductions in maximal voluntary torque (MVC; immediately postexercise onward, P < 0.001) and increased creatine kinase (from 24 h onward, P = 0.001), with both responses being attenuated following the second bout ( P < 0.015), demonstrating adaptation. Smaller reductions in MVC following both bouts occurred in older adults ( P = 0.005). Intracortical facilitation showed no changes ( P ≥ 0.245). Motor-evoked potentials increased 24 and 72 h postexercise in young ( P ≤ 0.038). Torque variability ( P ≤ 0.041) and H-reflex size ( P = 0.024) increased, while short-interval intracortical inhibition (SICI; P = 0.019) and the silent period duration (SP) decreased ( P = 0.001) in both groups immediately postexercise. The SP decrease was smaller following the second bout ( P = 0.021), and there was an association between the change in SICI and reduction in MVC 24 h postexercise in young adults ( R = −0.47, P = 0.036). Changes in neurophysiological responses were mostly limited to immediately postexercise, suggesting a modest role in adaptation. In young adults, neural inhibitory changes are linked to the extent of MVC reduction, possibly mediated by the muscle damage–related afferent feedback. Older adults incurred less muscle damage, which has implications for exercise prescription.

NEW & NOTEWORTHY This is the first study to have collectively assessed the role of corticospinal, spinal, and intracortical activity in muscle damage attenuation following repeated bouts of exercise in young and older adults. Lower levels of muscle damage in older adults are not related to their neurophysiological responses. Neural inhibition transiently changed, which might be related to the extent of muscle damage; however, the role of processes along the corticospinal pathway in the adaptive response is limited.
Propolis as an Adjuvant in the Healing of Human Diabetic Foot Wounds Receiving Care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca
Authors: Mujica Verónica , Orrego Roxana , Fuentealba Roberto , Leiva Elba , Zúñiga-Hernández Jessica
Published: September 2019

Objective. Diabetic foot wounds are a relevant diabetes complication and a major health problem. It has been described that propolis has health benefits due to its anti-inflammatory, antioxidant, and support in the healing process. The current study assessed the effect of propolis as an adjuvant in the healing of human diabetic foot ulcers. This was evaluated in a randomized placebo-controlled study of subjects receiving care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca, Chile. Research Design and Methods. Randomized subjects received ambulatory healing treatment for diabetes foot wounds with propolis spray (3%), which was applied to cover the entire wound surface each time it was dressed from week 0 until cicatrization or 8 weeks as a maximum. Two serum samples were taken (day 0 and end of the study) for cytokine and oxidative stress analyses. Also, macro- and microscopy were analyzed in the process of wound healing. Results. The study comprised 31 subjects with type 2 diabetes in treatment for diabetic foot wounds in the Diagnostic and Treatment Centre from the Regional Hospital of Talca. Propolis promotes a reduction of the wound’s area by an average of 4 cm2, related to an increase in the connective tissue deposit compared to the control. Also, propolis increased the glutathione (GSH) and GSH/glutathione disulfide (GSSG) ratio (p<0.02), depleted tumor necrosis factor- (TNF-) α, and increased interleukin- (IL-) 10 levels. Topical propolis did not modify the biochemical parameters in the serum of the studied subjects. Conclusions. The topical use of propolis turned out to be an interesting therapeutic strategy as an adjuvant in the care of diabetes foot wounds due to its ability to improve and promote healing based on its anti-inflammatory and antioxidant profile. This trial is registered with NCT03649243.
Simultaneous Purification and Separation of Syringoside and Oleuropein from Syringa oblata Lindl. Extract Using Macroporous Resin
Authors: Li Guoliang , Yan Hongxiu , Liu Xiangping
Published: September 2019

This study developed an efficient method to simultaneously separate and purify syringoside and oleuropein from Syringa oblata Lindl. extract using macroporous resins. The adsorption and desorption property of 11 resins were systematically evaluated. Based on the adsorption performance, HPD-100B resin was selected for the separation of syringoside and oleuropein. The HPD-100B resin fitted well to the Langmuir isotherm model (R2 > 0.97), as ascertained by the results of the static adsorption experiment. Kinetic and dynamic adsorption/desorption experiments were conducted using the HPD-100B resin to optimize the separation parameters of syringoside and oleuropein. On the optimal parameters, syringoside and oleuropein were obtained from the 20% and 40% ethanol eluates, respectively. In addition, the adsorption effluent (15–60 BV) contained a large amount of syringoside with less impurities; therefore, this part was also collected for further syringoside separation and enrichment of syringoside. By only one cycle treatment, the syringoside and oleuropein contents in the final products increased by 7.1-fold and 8.2-fold, respectively, compared to the initial extract. The method developed in this study provides a potential basis for the industrial-scale enrichment and separation of syringoside and oleuropein from S. oblata extract.
Lipid-Rich Extract from Mexican Avocado Seed (Persea americanavar. drymifolia) ReducesStaphylococcus aureusInternalization and Regulates Innate Immune Response in Bovine Mammary Epithelial Cells
Authors: Báez-Magaña Marisol , Ochoa-Zarzosa Alejandra , Alva-Murillo Nayeli , Salgado-Garciglia Rafael , López-Meza Joel Edmundo
Published: September 2019

Bovine mammary epithelial cells (bMECs) are capable of initiating an innate immune response (IIR) to invading bacteria.Staphylococcus aureusis not classically an intracellular pathogen, although it has been shown to be internalized into bMECs.S. aureusinternalizes into nonprofessional phagocytes, which allows the evasion of the IIR and turns antimicrobial therapy unsuccessful. An alternative treatment to control this pathogen is the modulation of the innate immune response of the host. The Mexican avocado (Persea americanavar. drymifolia) is a source of molecules with anti-inflammatory and immunomodulatory properties. Hence, we analyze the effect of a lipid-rich extract from avocado seed (LEAS) onS. aureusinternalization into bMECs and their innate immunity response. The effects of LEAS (1-500 ng/ml) on theS. aureusgrowth and bMEC viability were assessed by turbidimetry and MTT assays, respectively. LEAS did not show neither antimicrobial nor cytotoxic effects.S. aureusinternalization into bMECs was analyzed by gentamicin protection assays. Interestingly, LEAS (1-200 ng/ml) decreased bacterial internalization (60-80%) into bMECs. This effect correlated with NO production and the induction of the gene expression of IL-10, while the expression of the proinflammatory cytokine TNF-αwas reduced. These effects could be related to the inhibition of MAPK p38 (∼60%) activation by LEAS. In conclusion, our results showed that LEAS inhibits theS. aureusinternalization into bMECs and modulates the IIR, which indicates that avocado is a source of metabolites for control of mastitis pathogens.
The Clinical Features and Risk Factors of Parenchymal Neuro-Behcet’s Disease
Authors: Yan Dong , Liu JinJing , Zhang Yuehua , Yuan Wei , Xu Yan , Shi Jing , Li Chaoran , Wang Yining , Peng Linyi , Yang Yunjiao , Zhou Jiaxin , Wu Di , Liu Zhichun , Zeng Xiaofeng , Zhang Fengchun , Zheng Wenjie , Zhao Yan
Published: September 2019

To investigate the clinical features of parenchymal neuro-Behcet’s disease (p-NBD), we retrospectively reviewed the medical records of 1009 BD patients admitted to Peking Union Medical College Hospital from 2000 to 2016. Forty-two patients (25 males and 17 females) with p-NBD and eighty-four age- and sex-matched BD patients without neurological involvement who were served as controls were enrolled. Neurological onset was concomitant with the onset of BD in six cases (14.3%). Pyramidal signs (50.0%) and headache (33.3%) were the most common manifestations. On MRI, the lesions were mainly in the midline structures and hyperintense in the T2-weighted image. The most common lesion was the brainstem (54.8%). Spinal cord involvement was observed in five cases, four of which with cervical cord involvement. Multifocal lesions were observed in 13 patients. Ocular involvement was more prevalent in p-NBD (35.7%) (P=0.041, OR=2.36, 95% CI=1.03-5.44) compared with controls. All patients received corticosteroids and immunosuppressants, mainly cyclophosphamide (39/42). Six patients with severe/refractory condition received biological agents and achieved response measured by decreased Rankin score (P=0.002). With a median follow-up of 28 months, 22 patients (61.1%) achieved clinical improvements, while 10 (27.8%) relapsed and 4 died (mortality rate 11.1%). p-NBD is a rare yet disabling and life-threatening complication of BD. Ocular involvement is a risk factor for p-NBD. Promptly aggressive treatment is essential for improving prognosis, and biological agents might be a promising approach for severe/refractory p-NBD.
Protective Effects of Oridonin on Acute Liver Injury via Impeding Posttranslational Modifications of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) in the Toll-Like Receptor 4 (TLR4) Signaling Pathway
Authors: Shi Min , Deng Yilin , Yu Heguo , Xu Ling , Shi Cuicui , Chen Jiong , Li Guangming , Du Yiqi , Wang Yu-gang
Published: September 2019

Objective. Recent researches have demonstrated that inflammation-related diseases are effectively regulated by posttranslational modifications (PTMs) including phosphorylation and acetylation. Our previous study found a new acetyltransferase inhibitor, oridonin, which had a protective effect on acute liver injury (ALI). In the present study, we further investigated its protective mechanism against D-galactosamine (D-Gal) combined with lipopolysaccharide- (LPS-) induced ALI in mice. Methods. Intraperitoneal injections of LPS (40 μg/mouse)/D-Gal (5 mg/mouse) were given to the mice, and the experimental group was pretreated with intraperitoneal injection of oridonin (0.2 mg/mouse). To elucidate the protective mechanism of oridonin, we collected liver specimens and used RNA-sequencing (RNA-Seq) analysis. We focused on the genes that were upregulated by LPS/D-Gal and downregulated after pretreatment with oridonin. The downregulated genes examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were further verified by real-time polymerase chain reaction (PCR) and western blot. Results. GO analysis showed that genes that were downregulated after pretreatment with oridonin were extremely concentrated in immune response, chemotaxis, and inflammatory response. Real-time PCR confirmed that the expression of these genes was upregulated by LPS/D-Gal induction and reduced after treatment with oridonin, which was consistent with RNA-Seq results. KEGG pathway analysis showed a significantly enriched downregulated gene that was present in the Toll-like receptor (TLR) 4 signaling cascade. Our results manifested that phosphorylation levels of upstream signaling molecules in the TLR4 signaling cascade, including extracellular signal-regulated kinase (ERK), P38, and IκB, were significantly inhibited by oridonin. Furthermore, LPS/D-Gal stimulation triggered posttranslational modifications of related gene loci in the TLR4 signaling pathway, including phosphorylation of IL-1 receptor-associated kinase 4 (IRAK4 T345/S346) and acetylation of IRAK4 (K34). However, after treatment with oridonin, the modification pattern of IRAK4 expression stimulated by LPS/D-Gal was suggestively attenuated. Conclusion. Our study revealed that the protective effects of oridonin on LPS/D-Gal-induced ALI mediated by inhibition of the PTMs of IRAK4, including phosphorylation of T345/S346 and acetylation of K34.
Perspectives for Consideration in the Development of Microbial Cell Reference Materials
Authors: Allen-Vercoe Emma , Carmical Joseph Russell , Forry Samuel P. , Gail Mitchell H. , Sinha Rashmi
Published: September 2019

Microbiome measurement and analyses benefit greatly from incorporation of reference materials as controls. However, there are many points to consider in defining an ideal whole-cell reference material standard. Such a standard would embody all the diversity and measurement challenges present in real samples, would be completely characterized to provide “ground truth” data, and would be inexpensive and widely available. This ideal is, unfortunately, not readily attainable because of the diverse nature of different sequencing projects. Some applications may benefit most from highly complex reference materials, while others will value characterization or low expense more highly. The selection of appropriate microbial whole-cell reference materials to benchmark and validate microbial measurements should be considered carefully and may vary among specific applications. In this article, we describe a perspective on the development of whole-cell microbial reference materials for use in metagenomics analyses.
Ultrasmall Core-Shell Silica Nanoparticles for Precision Drug Delivery in a High-Grade Malignant Brain Tumor Model
Authors: Juthani Rupa , Madajewski Brian , Yoo Barney , Zhang Li , Chen Pei-Ming , Chen Feng , Turker Melik Z. , Ma Kai , Overholtzer Michael , Longo Valerie A. , Carlin Sean , Aragon-Sanabria Virginia , Huse Jason , Gonen Mithat , Zanzonico Pat , Rudin Charles M. , Wiesner Ulrich , Bradbury Michelle S. , Brennan Cameron W.
Published: September 2019

Purpose:

Small-molecule inhibitors have revolutionized treatment of certain genomically defined solid cancers. Despite breakthroughs in treating systemic disease, central nervous system (CNS) metastatic progression is common, and advancements in treating CNS malignancies remain sparse. By improving drug penetration across a variably permeable blood–brain barrier and diffusion across intratumoral compartments, more uniform delivery and distribution can be achieved to enhance efficacy.

Experimental Design:

Ultrasmall fluorescent core-shell silica nanoparticles, Cornell prime dots (C' dots), were functionalized with αv integrin-binding (cRGD), or nontargeting (cRAD) peptides, and PET labels (124I, 89Zr) to investigate the utility of dual-modality cRGD-C' dots for enhancing accumulation, distribution, and retention (ADR) in a genetically engineered mouse model of glioblastoma (mGBM). mGBMs were systemically treated with 124I-cRGD- or 124I-cRAD-C' dots and sacrificed at 3 and 96 hours, with concurrent intravital injections of FITC-dextran for mapping blood–brain barrier breakdown and the nuclear stain Hoechst. We further assessed target inhibition and ADR following attachment of dasatinib, creating nanoparticle–drug conjugates (Das-NDCs). Imaging findings were confirmed with ex vivo autoradiography, fluorescence microscopy, and p-S6RP IHC.

Results:

Improvements in brain tumor delivery and penetration, as well as enhancement in the ADR, were observed following administration of integrin-targeted C' dots, as compared with a nontargeted control. Furthermore, attachment of the small-molecule inhibitor, dasatinib, led to its successful drug delivery throughout mGBM, demonstrated by downstream pathway inhibition.

Conclusions:

These results demonstrate that highly engineered C' dots are promising drug delivery vehicles capable of navigating the complex physiologic barriers observed in a clinically relevant brain tumor model.
Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension
Authors: Chowdhury Mohammed Andaleeb , Moukarbel George V. , Gupta Rajesh , Frank Stephanie Marie , Anderson Ann M. , Liu Lijun C. , Khouri Samer J.
Published: September 2019

Background: The prevalence of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is increasing. We aim to study the role of big endothelin 1 (Big ET1), endothelin 1 (ET1), and neprilysin (NE) in HFpEF with PH. Method: This was a single center prospective cohort study including 90 HFpEF patients; 30 with no PH, 30 with postcapillary PH, and 30 with combined post- and precapillary PH. After enrollment, pulmonary venous and pulmonary arterial samples of Big ET1, ET1, and NE were collected during right heart catheterization. Subjects were then followed long term for adverse outcomes which included echocardiographic evidence of right ventricular dysfunction, heart failure hospitalization, and all-cause mortality. Results: Patients with HFpEF-PH were found to have increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) compared to controls (2.3 ± 1.4 and 1.6 ± 0.9 pg/mL, respectively). ET1W levels were associated with both PH (OR 2.7, 95% CI 1.5–4.7, p = 0.01) and pulmonary vascular resistance (OR 1.6, 95% CI 1.04–2.3, p = 0.03). No evidence of right ventricular dysfunction was observed after 1 year of follow-up. ET1W (OR 1.8, 95% CI 1.2–2.6, p = 0.01) and ET1 gradient (ET1G; OR 1.4, 95% CI 1.04–2, p = 0.03) were predictive of 1-year hospitalization. ET1G ≥0.2 pg/mL was associated with long-term mortality (log-rank 4.8, p = 0.03). Conclusion: In HFpEF patients, ET1W and ET1G are predictive of 1-year heart failure hospitalization, while elevated ET1G levels were found to be associated with long-term mortality in HFpEF. This study highlights the role of ET1 in developing PH in HFpEF patients and also explores the potential of ET1 as a prognostic biomarker.
AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice
Authors: Youngblood Bradford A. , Brock Emily C. , Leung John , Falahati Rustom , Bryce Paul J. , Bright Jessica , Williams Jason , Shultz Leonard D. , Greiner Dale L. , Brehm Michael A. , Bebbington Christopher , Tomasevic Nenad
Published: September 2019

Introduction: Pathologic accumulation and activation of mast cells and eosinophils are implicated in allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is an inhibitory receptor selectively expressed on mast cells, eosinophils and, at a lower extent, basophils. When engaged with an antibody, Siglec-8 can induce apoptosis of activated eosinophils and inhibit mast cell activation. AK002 is a humanized, non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases. Here we examine the human tissue selectivity of AK002 and evaluate the in vitro, ex vivo, and in vivo activity of AK002 on eosinophils and mast cells. Methods: The affinity of AK002 for Siglec-8 and CD16 was determined by biolayer interferometry. Ex vivo activity of AK002 on human eosinophils from blood and dissociated human tissue was tested in apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. The in vivo activity of a murine precursor of AK002 (mAK002) was tested in a passive systemic anaphylaxis (PSA) humanized mouse model. Results: AK002 bound selectively to mast cells, eosinophils and, at a lower level, to basophils in human blood and tissue and not to other cell types examined. AK002 induced apoptosis of interleukin-5-activated blood eosinophils and demonstrated potent ADCC activity against blood eosinophils in the presence of natural killer cells. AK002 also significantly reduced eosinophils in dissociated human lung tissue. Furthermore, mAK002 prevented PSA in humanized mice through mast cell inhibition. Conclusion: AK002 selectively evokes potent apoptotic and ADCC activity against eosinophils and prevents systemic anaphylaxis through mast cell inhibition.
The Blockade of µ1- and κ-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain
Authors: Calvo Fabrício , Almada Rafael Carvalho , da Silva Juliana Almeida , Medeiros Priscila , da Silva Soares Jr. Raimundo , de Paiva Yara Bezerra , Roncon Camila Marroni , Coimbra Norberto Cysne
Published: September 2019

Background: Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABAA receptor-mediated system in the IC on panic-like responses. Methods: The effect of the blockade of either µ1- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABAA antagonism with bicuculline. Microinjections of naloxonazine, a µ1-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABAA-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded. Results: GABAA-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses. Conclusions: These findings suggest a role played by µ1- and κ-OR-containing connexions and GABAA receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.
Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma
Authors: Sautter Lisa , Hofheinz Ralf , Tuettenberg Jochen , Grimm Mario , Vajkoczy Peter , Groden Christoph , Schmieder Kirsten , Hochhaus Andreas , Wenz Frederik , Giordano Frank A.
Published: September 2019

Purpose:Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. Methods: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0–2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. Results: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5–30) months in arm A and 6.5 (0.3–51.5) months in arm B. The median PFS was 2.8 months (95% CI 0–8.7) in arm A and 2.1 months (95% CI 0–11.8) in arm B. The median OS was 5.0 (0.8–30) months (95% CI 0–24.1) in arm A and 6.5 (0.3–51.5) months (95% CI 0–32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). Conclusions: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.
O Eclipse de Sobral e a deflexão gravitacional da luz predita por Einstein
Authors: Matsuura Oscar Toshiaki
Published: September 2019

Este artigo é comemorativo do centenário do eclipse total do Sol ocorrido em 29/5/1919, cujos dados observacionais coletados por duas equipes britânicas deram lugar a um fato marcante da História da Ciência: a confirmação da deflexão da luz pelo Sol predita por Einstein, o que o entronizou da noite para o dia no panteão dos gênios da humanidade; e o lançamento ao mundo da Teoria da Relatividade Geral. Mas esse eclipse diz respeito especialmente a nós, brasileiros, pois foi observado por uma das equipes britânicas em Sobral, CE. Para o bom entendimento desse acontecimento, a curiosa ideia de que a luz pode deixar de caminhar em linha reta, será discutida desde seus primeiros registros. A formulação dessa ideia seguiu pari passu a elaboração da Relatividade Geral, ou melhor, a transição da Relatividade Restrita de 1905 à Relatividade Geral de 1915. A possibilidade da detecção num eclipse da deflexão da luz, um dos testes da validade da Relatividade Geral, mobilizou astrônomos de vários países por muitos anos. No eclipse de 1919 foi anunciada bombasticamente a confirmação da deflexão da luz e a validação da Relatividade Geral. Nesta parte, também visando o bom entendimento, o presente trabalho é suplementado com esclarecimentos sobre termos técnicos e sobre procedimentos de observação fotográfica e análise de imagens. A discussão e a proclamação dos resultados e a posterior “supercomprovação” da deflexão da luz serão discutidas à luz dos estudos de astrônomos e físicos, historiadores e filósofos da ciência realizados nestes 100 anos desde o eclipse, com o intuito de propor ao leitor uma reflexão, não só sobre os avanços conceituais e tecnológicos da ciência, mas sobretudo sobre as novas avaliações acerca da validade do conhecimento científico, da incidência dos fatores sociológicos e menos racionais na construção desse conhecimento. Nos bastidores da comunidade científica o anúncio bombástico dos resultados do eclipse de 1919 não foi simples e direto como as manchetes da época e algumas atuais, ainda insistem em nos fazer crer. Esta é a oportunidade para uma retificação, em benefício de uma percepção realista e não falsamente idealizada da ciência e dos cientistas.
O Estudo de Claudio Galeno como Fonte de Conhecimento da Anatomia Humana
Authors: Stülp Camille Bertha , Mansur Samira Schultz
Published: September 2019

A anatomia humana foi estudada formalmente pela primeira vez no Egito e logo se caracterizou por observações diretas e princípios da filosofia, já que a sua compreensão dá-se à luz da evolução dos seres. Esta pesquisa objetivou compreender o estudo de Galeno como fonte de conhecimento da anatomia humana, além de descrever a sua biografia com ênfase em suas contribuições à anatomia humana e relacionar seus achados e exegese anatômica frente às descobertas de outros filósofos. Concluiu-se que a compreensão da anatomia exige o resgate social e cultural da Grécia, onde os primeiros filósofos viveram, e que a ideologia de Galeno teve como cerne a sua criatividade e a sua originalidade.
O jornal estudantil do período de 1964-2013 como fonte de pesquisa em formato digital no acervo do Centro de Memória e Arquivo da FCM-Unicamp.
Authors: Amaral Ivan Luiz Martins Franco do , Souza Rodrigo Lizardi de , Antunes Raíssa Malto , Poderoso Rosana Evangelista
Published: September 2019

Este artigo é o estudo completo da apresentação realizada no 2º Congresso de História da Ciência e da Técnica: Desafios Contemporâneos. Os arquivos históricos apresentam um papel fundamental no desenvolvimento e surgimento das pesquisas históricas. A utilização de ferramentas tecnológicas e o trabalho de resgate de acervos de documentação primária são exemplos de desafios contemporâneos das pesquisas. O objetivo deste trabalho é apresentar e descrever a inserção do conjunto documental O Patológico na coleção do Centro de Memória e Arquivo da FCM-Unicamp, em parceria com o Arquivo Central da Unicamp e Biblioteca da Faculdade. Desta parceria, resultou a digitalização de todo o conjunto em PDF/A pesquisável, em formato de preservação digital – este padrão promove agilidade de acesso ao documento para o usuário.
O futuro entre o lazer e a alienação
Authors: Andrioni Fabio Sapragonas
Published: September 2019

Este artigo aborda o conceito de “sociedade pós-industrial” apresentado no livro The year 2000, lançado em 1967 e escrito por Herman Kahn e Anthony J. Wiener. Este conceito resulta da compreensão de história dos autores a partir da ideia de tendência múltipla. Esta tendência é uma relação de outras tendências, as quais vêm de séculos atrás, e sua extrapolação resulta em um desenvolvimento por estágios econômicos. Todavia, os autores não apresentam a sociedade pós-industrial de uma só maneira, mas a partir de várias possibilidades, algumas consideradas boas e outras, ruins. As diversas possibilidades abrangem questões culturais e sociais, construindo, enfim, uma teoria de desenvolvimento.
A report on the herpetofauna of Tengchong Section of Gaoligongshan National Nature Reserve, China
Authors: Yang Jian-Huan , Huang Xiang-Yuan , Ye Jian-Fang , Yang Shen-Pin , Zhang Xing-Chao , Chan Bosco Pui Lok
Published: September 2019

We present the results from a series of herpetological surveys conducted in the Tengchong Section of Gaoligongshan National Nature Reserve, Yunnan Province, China between April 2014 and November 2018.  A total of 59 species of amphibians and reptiles (one salamander, 30 batrachians, four lizards, and 24 snakes) were recorded during the surveys including three newly described amphibian species and 17 new records for Tengchong, 10 of which also represent new generic records for the area.  Natural history notes of some little-known species are presented.  Our survey results clearly demonstrate that the herpetofauna diversity of this mountain range is still underestimated and warrants further systematic study.
Invasive Management of Out of Hospital Cardiac Arrest
Authors: Kelly Erik M. , Pinto Duane S.
Published: September 2019

Out of hospital cardiac arrest (OHCA) is a major cause of morbidity and mortality worldwide. Clinical decision making is extremely difficult in this understudied patient population with high prevalence of neurological injury and inexorable shock states. As such, there are uncertain benefits from therapies available in the cardiac catheterization laboratory. Fear of futility and public reporting often affects decision making and can result in risk aversion. This review focuses on invasive management in OHCA care, with particular focus on coronary angiography, coronary revascularization, and mechanical support. Guidelines recommend emergency coronary angiography in patients with ST-segment elevations on ECG after OHCA, while the role of coronary angiography in patients without ST-segment elevations is less clear. Similar uncertainty remains in the appropriate revascularization strategy in these patients. As in other areas of cardiology, there is a growing interest in the role of mechanical circulatory support after OHCA, though the available literature shows mixed results. The many uncertainties associated with treating the patient with OHCA highlight the importance of clinical decision support tools and treatment algorithms in the care of this population. This review focuses on invasive management in OHCA care, with particular focus on coronary angiography, coronary revascularization, and mechanical support.
ATRQβ‐001 Vaccine Prevents Experimental Abdominal Aortic Aneurysms
Authors: Zhang Hongrong , Liao Mengyang , Cao Mingsi , Qiu Zhihua , Yan Xiaole , Zhou Yanzhao , Wu Hailang , Wang Yingxuan , Zheng Jiayu , Ding Jiaxing , Wang Min , Liao Yuhua , Chen Xiao
Published: September 2019

Background

We have developed a peptide vaccine named
ATRQ
β‐001, which was proved to retard signal transduction initiated by angiotensin
II
(Ang II). Ang
II
was implicated in abdominal aortic aneurysm (
AAA
) progression, but whether the
ATRQ
β‐001 vaccine would prevent
AAA
is unknown.

Methods and Results

Ang
II
‐infused ApoE
−/−
mice and calcium phosphate‐induced
AAA
in C57
BL
/6 mice were used to verify the efficiency of
ATRQ
β‐001 vaccine in
AAA
. Results demonstrated that the vaccine effectively restrained the aneurysmal dilation and vascular wall destruction of aorta in both animal models, beyond anti‐hypertensive effects. In Ang
II
‐induced
AAA
vascular sections, Immunohistochemical staining showed that the vaccine notably constrained vascular inflammation and vascular smooth muscle cell (
VSMC
) phenotypic transition, concurrently reduced macrophages infiltration. In cultured
VSMC
, the anti‐
ATR
‐001 antibody inhibited osteopontin secretion induced by Ang
II
, thereby impeded macrophage migration while co‐culture. Furthermore, metalloproteinases and other matrix proteolytic enzymes were also found to be limited by the vaccine in vivo and in vitro.

Conclusions

ATRQ
β‐001 vaccine prevented
AAA
initiation and progression in both Ang
II
and calcium phosphate‐induced
AAA
models. And the beneficial effects were played beyond decrease of blood pressure, which provided a novel and promising method to take precautions against
AAA
.
Receipt of American Heart Association–Recommended Preconception Health Care Among Privately Insured Women With Congenital Heart Defects, 2007–2013
Authors: Farr Sherry L. , Downing Karrie F. , Ailes Elizabeth C. , Gurvitz Michelle , Koontz Gretchen , Tran Emmy L. , Alverson C. J. , Oster Matthew E.
Published: September 2019

Background

Our objective was to estimate receipt of preconception health care among women with congenital heart defects (
CHD
), according to 2017 American Heart Association recommendations, as a baseline for evaluating recommendation implementation.

Methods and Results

Using 2007 to 2013
IBM
MarketScan Commercial Databases, we identified women with
CHD
diagnosis codes ages 15 to 44 years who became pregnant and were enrolled in health insurance for ≥11 months in the year before estimated conception. We assessed documentation of complete blood count, electrolytes, thyroid‐stimulating hormone, liver function, ECG, comprehensive echocardiogram, and exercise stress test, using procedural codes, and outpatient prescription claims for US Food and Drug Administration category D and X cardiac‐related medications. Differences were examined according to
CHD
severity, age, region of residence, year of conception, and documented encounters at obstetric and cardiology practices. We found 2524 pregnancies among 2003 women with
CHD
(14.4% severe
CHD
). In the 98.3% of women with a healthcare encounter in the year before conception, <1% received all and 22.6% received no American Heart Association–recommended tests or assessments (range: 54.4% for complete blood count to 3.1% for exercise stress test). Women with the highest prevalence of receipt of recommended care were 35 to 44 years old, pregnant in 2012 to 2013, or had a documented obstetric or cardiology encounter in the year before conception (
P
<0.05 for all). In 9.0% of pregnancies, ≥1 prescriptions for US Food and Drug Administration category D or X cardiac‐related medications were filled in the year before conception.

Conclusions

A low percentage of women with
CHD
received American Heart Association–recommended preconception health care in the year before conception.