bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of inhibitors of specific carboxylesterases: Development of carboxylesterase inhibitors for translational application
Authors: Yoon Kyoung Jin P. , Hyatt Janice L. , Morton Christopher L. , Lee Richard E. , Potter Philip M. , Danks Mary K.
Published: June 2022

Carboxylesterases, expressed at high levels in human liver and intestine, are thought to detoxify xenobiotics. The anticancer prodrug 7-ethyl-10-[4-1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is also metabolized by carboxylesterases to produce the active drug 7-ethyl-10-hydroxycamptothecin. Activation of CPT-11 by human intestinal carboxylesterase (hiCE) in the human intestine may contribute to delayed onset diarrhea, a dose-limiting side effect of this drug. The goal of this study was to develop small molecule inhibitors selective for hiCE to circumvent or treat the toxic side effects of CPT-11. A secondary goal was to develop molecules that specifically inhibit activation of CPT-11 by a rabbit liver carboxylesterase (rCE). rCE is the most efficient CPT-11–activating enzyme thus far identified, and this enzyme is being developed for viral-directed enzyme prodrug therapy applications. Based on in vitro assays with partially purified hiCE and rCE proteins and on growth inhibition assays using U373MG human glioma cells transfected to express hiCE or rCE (U373pIREShiCE or U373pIRESrCE), we identified specific inhibitors of each enzyme. Lead compounds are derivatives of nitrophenol having 4-(furan-2-carbonyl)-piperazine-1-carboxylic acid or 4-[(4-chlorophenyl)-phenylmethyl]-piperazine-1-carboxylic acid substitutions in the p position. Kinetic analysis of each compound for hiCE compared with rCE showed that the Ki values of the most selective of these inhibitors differed by 6- to 10-fold. In growth inhibition assays, nontoxic, low micromolar concentrations of these inhibitors increased the EC50 of CPT-11 for U373pIREShiCE or U373pIRESrCE cells by 13- to >1,500-fold. The four compounds characterized in this study will serve as lead compounds for a series of inhibitors to be constructed using a combinatorial approach.
Treatment of experimental breast cancer using interleukin-12 gene therapy combined with anti–vascular endothelial growth factor receptor-2 antibody
Authors: Rakhmilevich Alexander L. , Hooper Andrea T. , Hicklin Daniel J. , Sondel Paul M.
Published: June 2022

We have shown previously that interleukin-12 (IL-12) gene therapy induced strong antitumor effects in several syngeneic murine tumor models including 4T1 mammary adenocarcinoma. Antiangiogenic treatment with a monoclonal antibody (mAb) directed against the vascular endothelial growth factor receptor-2 (VEGFR-2) is another promising treatment approach that can cause transient suppression of tumor growth. We hypothesized that the combination of IL-12 gene therapy and anti-VEGFR-2 mAb will achieve better antitumor and antimetastatic effects against 4T1 adenocarcinoma than each treatment alone via implementation of different mechanisms. Administration of anti-VEGFR-2 mAb into BALB/c mice bearing s.c. 4T1 tumors induced significant suppression of tumor growth, as did intratumoral administration of naked IL-12 DNA. The combined treatment with anti-VEGFR-2 mAb and IL-12 DNA resulted in significantly enhanced inhibition of tumor growth as compared with each treatment alone. This combination was also effective against spontaneous lung metastases. In T-cell–deficient nude mice, both IL-12 DNA and anti-VEGFR-2 mAb were effective in suppressing tumor growth. In T-cell- and natural killer cell–deficient scid/beige mice, only anti-VEGFR-2 mAb was effective, suggesting that natural killer cells are involved in the antitumor effects induced by IL-12 DNA. In both types of immunodeficient mice, the combination of anti-VEGFR-2 mAb and IL-12 DNA was as effective in suppressing 4T1 tumor growth as anti-VEGFR-2 mAb alone. Antitumor effects of anti-VEGFR-2 mAb were associated with the inhibition of angiogenesis within the tumors, whereas the antiangiogenic effect of IL-12 gene therapy was not detected. Our results show a therapeutic benefit of combining IL-12 gene therapy and anti-VEGFR-2 mAb for cancer treatment.
Genomic Features of Interstitial Deletions of Chromosome 9q in Acute Myeloid Leukemia
Authors: Qi Zhongxia , Wen Kwun Wah , Ki Anita , Prakash Sonam , Kogan Scott , Yu Jingwei
Published: June 2022

Interstitial deletion in the long arm of chromosome 9 [del(9q)] is a fairly common cytogenetic finding associated with acute myeloid leukemia (AML), seen in approximately 2–5% of AML patients. However, the genomic features of the deletion remain largely unknown. Using chromosome analysis, single nucleotide polymorphism microarray, and next-generation sequencing, we characterized del(9q)s and other genomic alterations in 9 AML patients. We found several distinct features of the del(9q)s. The proximal breakpoints of the deletions are clustered within a 2.5-Mb region (chr9: 68,513,625–70,984,372; GRCh37) enriched with segmental duplications, which may represent a “hotspot” for genomic rearrangements. However, the distal breakpoints of the deletions vary significantly. In addition, the overall deleted region could be divided into a 14.4-Mb proximal constitutional region (chr9: 70,950,015–85,397,699; 9q21.11q21.32) and a 24.0-Mb distal oncogenic region (chr9: 85,397,700–109,427,261; 9q21.32q31.1). We further identified a 6.8-Mb common overlapped deletion region (CODR) in the distal region (chr9: 90,590,650–97,366,400). This CODR carries multiple genes that are reportedly involved in cancer pathogenesis. The prognostic value of the del(9q) in AML apparently depends on additional genomic alterations in the patients.
Stroke Severity among Men and Women Acute Ischemic Stroke Patients in the Telestroke Network
Authors: Poupore Nicolas , Edrissi Camron , Sowah Mareshah , Stanley Madison , Joffe Jonah , Lewis Donovan , Cunningham Taylor , Sanders Carolyn Breauna , Knisely Krista , Rathfoot Chase , Nathaniel Thomas I.
Published: June 2022

Introduction: This study investigates gender differences among stroke patients treated in the telestroke network using specific risk factors that contribute to stroke severity. Methods: We examined gender differences in stroke severity among 454 patients hospitalized with acute ischemic stroke (AIS). The logistic regression model was used to predict clinical risk factors associated with stroke severity in men and women AIS patients. Results: In the adjusted analysis among women patients, increasing age (odds ratio [OR] = 1.05, 95% CI: 1.017–1.085, p = 0.003) and higher heart rate (OR = 1.031, 95% CI: 1.005–1.058, p = 0.021) were associated with worsening neurological functions, while direct admission (OR = 0.191, 95% CI: 0.079–0.465, p < 0.001) was associated with improving neurologic functions. Among men, hypertension (OR = 3.077, 95% CI: 1.060–8.931, p = 0.039) and higher international normalized ratio (INR) (OR = 21.959, 95% CI: 1.489–323.912, p = 0.024) were associated with worsening neurologic functions, while Caucasian (OR = 0.181, 95% CI: 0.062–0.526, p = 0.002) and obesity (OR = 0.449, 95% CI: 0.203–0.99, p = 0.047) were associated with neurologic improvement. Conclusion: Increasing age and heart rate in women, hypertension and greater INR in men contribute to worsening neurologic functions. There is a need to develop strategies to improve the care of both men and women in the telestroke network.
Interfaces da Medicina de Reabilitação com a Medicina do Trabalho e as Ciências Forenses
Authors: Battistella Linamara Rizzo
Published: June 2022

A Fisiatria é o reflexo da visão holística em saúde. A partir dos avanços farmacológicos, da imunologia, da assistência clínica em geral e do arsenal diagnóstico, a Medicina tem conseguido salvar muitas vidas; porém, este aumento de sobrevida foi acompanhado de um contingente cada vez maior de indivíduos portadores de grau maior ou menor de incapacidades, impossibilitados, depois de sua cura, de serem reintegrados ao ambiente de trabalho, à vida comunitária e até mesmo na sua independência para autocuidados.
Association of Genome-Wide Polygenic Risk Score for Body Mass Index With Cardiometabolic Health From Childhood Through Midlife
Authors: Shi Mengyao , Chen Wei , Sun Xiao , Bazzano Lydia A. , He Jiang , Razavi Alexander C. , Li Changwei , Qi Lu , Khera Amit V. , Kelly Tanika N.
Published: June 2022

Background:

Genetic information may help to identify individuals in childhood who are at increased risk for cardiometabolic disease.

Methods:

We included 1201 BHS (Bogalusa Heart Study) participants (832 White participants and 369 Black participants) who were followed up to 42.3 years, starting at a mean age of 9.8 years. A validated genome-wide polygenic risk score (PRS) was tested for association with midlife body mass index (BMI), fasting plasma glucose, and systolic blood pressure using multiple linear regression models. Cox proportional hazards models tested associations of the PRS with incident obesity, diabetes, and hypertension. All analyses were conducted according to race and adjusted for baseline age, sex, ancestry, and BMI.

Results:

The constructed PRS was significantly and modestly correlated with midlife BMI in both White and Black participants, with correlation coefficients of 0.27 (
P
=1.94×10
−8
) and 0.16 (
P
=5.50×10
−3
), respectively. In White participants, per SD increase of PRS was associated with an average 1.29 kg/m
2
higher BMI (
P
=4.44×10
−9
), 2.82 mg/dL higher fasting plasma glucose (
P
=1.17×10
−3
), and 1.09 mm Hg higher systolic blood pressure (
P
=3.57×10
−2
) at midlife. The PRS also conferred a 26% higher increased risk of obesity (
P
=3.50×10
−6
) in White participants. In addition, the variance in midlife BMI explained increased from 0.1973 to 0.2293 when PRS was added to the model including age, sex, principal components, and baseline BMI (
P
<0.0001). No associations were observed in Black participants.

Conclusions:

Adiposity-related genetic information independently predicted cardiometabolic health in White BHS participants. Null associations observed in Black BHS participants highlight the urgent need for PRS development in multi-ancestry populations.
Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring
Authors: Tong Wen , Allison Beth J. , Brain Kirsty L. , Patey Olga V. , Niu Youguo , Botting Kimberley J. , Ford Sage G. , Garrud Tessa A. , Wooding Peter F.B. , Shaw Caroline J. , Lyu Qiang , Zhang Lin , Ma Jin , Cindrova-Davies Tereza , Yung Hong Wa , Burton Graham J. , Giussani Dino A.
Published: June 2022

Background:

Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology.

Methods:

We adopted an integrative approach to investigate the inter-relationship between chronic hypoxia during pregnancy with maternal, placental, and fetal outcomes, common in preeclampsia. We exploited a novel technique using isobaric hypoxic chambers and in vivo continuous cardiovascular recording technology for measurement of blood pressure in sheep and studied the placental stress in response to hypoxia at cellular and subcellular levels.

Results:

Chronic hypoxia in ovine pregnancy promoted fetal growth restriction (FGR) with evidence of fetal brain-sparing, increased placental hypoxia-mediated oxidative damage, and activated placental stress response pathways. These changes were linked with dilation of the placental endoplasmic reticulum (ER) cisternae and increased placental expression of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), combined with a shift towards an angiogenic imbalance in the maternal circulation. Chronic hypoxia further led to an increase in uteroplacental vascular resistance and the fall in maternal blood pressure with advancing gestation measured in normoxic pregnancy did not occur in hypoxic pregnancy.

Conclusions:

Therefore, we show in an ovine model of sea-level adverse pregnancy that chronic hypoxia recapitulates physiological and molecular features of preeclampsia in the mother, placenta, and offspring.
Association Between Hypertension and Incident Infective Endocarditis
Authors: Lee Gyu Bae , Shin Koh Eun , Han Kyungdo , Son Ho-Sung , Jung Jae-Seung , Kim Yang-Hyun , Kim Hee-Jung
Published: June 2022

Background:

This study aimed to evaluate the association of hypertension with incident infective endocarditis (IE) by investigating the incidence of IE according to blood pressure levels using the National Health Insurance Service database.

Methods:

The data of 4 080 331 individuals linked to the health screening database in 2009 were retrieved (males, 55.08%; mean age, 47.12±14.13 years). From 2009 to 2018, the risk factors for the first episode of IE were investigated. Hypertension was categorized into normotension, prehypertension, hypertension, and hypertension with medication. The Cox proportional hazard model assessed the effect of blood pressure level during the health screening exam on incident IE.

Results:

During the 9-year follow-up, 812 (0.02%) participants were diagnosed with IE. The incidence rates of IE in the normotension, prehypertension, hypertension, and hypertension with medication groups were 0.9, 1.4, 2.6, and 6.0 per 100 000 person-years, respectively. Those with prehypertension, hypertension, and hypertension with medication were correlated with an increased risk of IE in a dose-response manner compared with the normotension group (hazard ratio, 1.33 [95% CI, 1.06–1.68]; hazard ratio, 1.98 [1.48–2.66]; hazard ratio, 2.56 [2.02–3.24], respectively, all
P
<0.001).

Conclusions:

In a large national cohort study with an average follow-up of 9 years, increased blood pressure was identified as a risk factor for incident IE in a dose-dependent manner. Hypertension increases the public health care burden by acting as a risk factor for rare infective heart diseases.
Structure and Dynamics of Islamic Social Formations (Seventh–Fourteenth Century)
Authors: Batou Jean
Published: June 2022

From the seventh to the fourteenth century, the Muslim world’s key actors were free peasants working limited and scattered cultivated areas, whose communities paid heavy taxes. A distinct nomadic mode of production dominated the arid lands and their warlike pastoral tribes. Wealthy merchants and artisans controlled urban ideological production, living next to actual ruling classes, who drew exceptional material privileges from their proximity to the state. Since the latter’s status contradicted the contractual community’s values, political power was socially alienated and needed support from paid soldiers and often co-opted religious notables. The author describes Islamic social formations as real flesh-and-blood beings who developed original features on the same tributary mode of production’s skeleton. He shows that comparable dialectical oppositions enlivened them, stemming from uneven and combined development processes. Thus, their states and villages, barren lands and city markets, contractual ideology and monarchical powers were permanently in conflictual interaction.
Revision of the New Zealand endemic genus Pseudoscelolabes Collin (Diptera: Hybotidae: Ocydromiinae)
Authors: BARROS LUANA MACHADO , SOARES MATHEUS MICKAEL MOTA , DE FREITAS-SILVA RAFAEL AUGUSTO PINHEIRO , SINCLAIR BRADLEY J. , ALE-ROCHA ROSALY
Published: June 2022

Pseudoscelolabes Collin, 1933, an endemic New Zealand genus, is revised, including the description of a new species, P. lesagei Sinclair & Barros sp. nov. The male and female terminalia of the genus are described and illustrated for the first time. An identification key to the two included species and a map with distribution records are provided. The relationships of the genus within Ocydromiinae are discussed.
Two new species of non-marine Ostracoda (Crustacea) of the genera Vestalenula Rossetti & Martens, 1998 (Darwinuloidea) and Microloxoconcha Hartmann, 1954 (Cytheroidea) from Tsushima, Japan, and a summary of the non-marine ostracod fauna of the island
Authors: SMITH ROBIN JAMES , CHANG CHEON YOUNG
Published: June 2022

The archipelago of Tsushima is located in the Korea Strait, at the southern end of the Sea of Japan (East Sea), and lies almost equidistant from Korea and Japan. Its non-marine ostracod fauna was previously unknown, although potentially of (palaeo-) zoogeographical interest considering its position. Preliminary surveys of freshwater and brackish habitats on the island in August/September and November/December 2019, revealed a total of 31 species in five families and three superfamilies. Two species are described as new. Vestalenula gravata sp. nov. is a small representative of the family Darwinulidae, characterized by a very long keel on the right valve and the absence of a pigmented eye. This species was found in very shallow streams with poorly sorted substrates in forests. Microloxoconcha semicircularis sp. nov., an interstitial Cytheroidea, was recovered from the tidal part of a small river, the first time this genus has been found in this type of habitat. Two other undescribed species are figured, but left in open nomenclature due to insufficient number of individuals: Vestalenula sp. and Cobanocythere sp. The antennule and antenna of Vestalenula sp. are most similar to those of three species from Brazil.
A Reflexive Critique of Inter-paradigm Divisions in International Relations Theory: On Anarchy, Hierarchy and Pre-1919 Theory
Authors: Ganchev Ivo
Published: June 2022

This article begins by re-opening the Third Great Debate which established division lines between mainstream (realist/liberal/constructivist) and Critical (neo-Marxist/neo-Gramscian) theories of International Relations based on their different assumptions about the nature of the international system: anarchy and hierarchy, respectively. The first half of the article argues that adopting common definitions of these concepts makes the anarchy–hierarchy debate theoretically irresolvable and further demonstrates that mainstream and Critical theories do not share an understanding of these terms neither between, nor within, their own traditions. The second half of this article challenges and aims to correct the interpretation of three key political thinkers, Halford J. Mackinder, W. E. B. DuBois and Norman Angell as appropriated within the inter-paradigm debates of International Relations. It argues that the respective associations of these thinkers with early realism, critical theories and early liberalism are intellectually misguiding because their works exhibit a common understanding of the ‘international’ across macro- and micro-dimensions, which is uncharacteristic of ‘-isms’. This shows that popular interpretations of pre-1919 works through post-1919 paradigms can obscure more than they reveal. These findings do not seek to present new ideas but to produce a reflexive critique of IR which illuminates some, perhaps unintended, counter-productive systemic effects that inter-paradigm divisions can have on the discipline.
Prepregnancy and Gestational Diabetes and Cessation of Breastfeeding <1 Week Postpartum, United States, 2016-2018
Authors: Kortsmit Katherine , Boone Kirsten I. , Warner Lee , Horan Jessica , Bower Julie K. , Gallo Maria F.
Published: June 2022

Objectives:

Diabetes may delay milk letdown, and perceiving milk production as insufficient can lead to breastfeeding cessation. We evaluated whether prepregnancy or gestational diabetes is associated with cessation of breastfeeding by 1 week postpartum.

Methods:

We analyzed 2016-2018 data from 42 sites in the Pregnancy Risk Assessment Monitoring System, a population-based survey of women with a recent live birth. Participants were surveyed 2-6 months after childbirth. We used logistic regression models to evaluate the relationship between prepregnancy or gestational diabetes only and breastfeeding <1 week postpartum among women who had initiated breastfeeding.

Results:

Among 82 050 women who initiated breastfeeding, 4.5% reported breastfeeding <1 week postpartum. Overall, 11.7% of women reported any history of diabetes in the 3 months before becoming pregnant; 3.3% reported prepregnancy diabetes, and 8.4% reported gestational diabetes only. In both unadjusted and adjusted models, the prevalence of breastfeeding <1 week postpartum did not differ significantly among women with prepregnancy diabetes or gestational diabetes only compared with women without any history of diabetes. The prevalence of breastfeeding <1 week postpartum was 4.4% among women without any history of diabetes, 5.6% among women with prepregnancy diabetes (adjusted prevalence ratio [aPR] = 1.15; 95% CI, 0.91-1.46), and 4.5% among women with gestational diabetes only (aPR = 1.01; 95% CI, 0.84-1.20).

Conclusions:

We found no association between a history of diabetes prepregnancy or gestational diabetes only and breastfeeding <1 week postpartum in a large, population-based survey of postpartum women who initiated breastfeeding. Regardless of their diabetes status, women who want to breastfeed might benefit from interventions that support their ability to continue breastfeeding.
L1 impedance control for bilateral teleoperation containing model uncertainty
Authors: Yazdankhoo Behnam , Ha’iri Yazdi Mohammad Reza , Najafi Farshid , Beigzadeh Borhan
Published: June 2022

Restricting transient peaks of contact force in teleoperation systems is undeniably vital, specially in critical applications such as telesurgery. This issue, however, has still remained unsolved in the literature. In order to address this problem, we propose an impedance control scheme using optimal L1 theory for teleoperation systems encompassing asymmetric randomly time-varying delays and model uncertainties. To this end, an L1-based state-feedback compensator is designed employing linear matrix inequalities, aiming at minimizing the desired impedance error subjected to human force as exogenous disturbance. A simulation is ultimately conducted in comparison with the sliding-mode-based impedance controller. The results validate that the proposed controller is able to keep the integral of impedance error within the desired bound and, thus, improves the transient response. This is, however, at the expense of imposing a steady-state error for the integral of impedance error, which is normally made zero by the sliding-mode controller.
Speckle Reduction in Ultrasound Images of the Common Carotid Artery Based on Integer and Fractional-Order Total Variation
Authors: Wang Kun , Li Zhiyao , Zhang Yufeng
Published: June 2022

Designing a technique with higher speckle noise suppressing capability, better edge preserving performance, and lower time complexity is a research objective for the common carotid artery (CCA) ultrasound despeckling. Total variation based techniques have been widely used in the image denoising and have good performance in preserving the edges in the images. However, the total variation based filters can produce the staircase artifacts. To address this issue, second-order total variation based techniques have been proposed for the image denoising. However, the previous study has been proved that the fractional differential model has better performance in reducing the speckles in ultrasound despeckling compared with the second-order model. Thus, to improve the performance of ultrasound despeckling and edge preserving, a novel despeckling model based on integer and fractional-order total variation (IFOTV) is proposed for CCA ultrasound images. Moreover, the minimization problems in our despeckling model are solved by the alternating direction method of multiplier (ADMM). In results with synthetic images, the edge preservation index (EPI) values of proposed method are 0.9524, 0.8797, and 0.7351 as well as 0.9137, 0.8253, and 0.6847 under three different levels of noise, which are the highest among four advanced methods. In results with simulated CCA ultrasound images, the speckle suppression and mean preservation indices of proposed method are 0.5596, 0.6571, and 0.8106 under three different levels of noise, which are the best among four advanced methods. In results with clinical images, the average absolute error of intima-media thickness measurements of proposed method is 0.0660 ± 0.0679 (mean ± std in mm), which is the lowest among four advanced methods. In conclusion, the IFOTV method has improved performance in suppressing the speckle noise and preserving the edge, and is thus a potential alternative to the current filters for the CCA ultrasound despeckling.
Oral health and knowledge of sighted children and children with visual impairment and their parents’ role in it: A comparative study
Authors: Cunha Soraia Ramos , Fátima Bizarra Maria de
Published: June 2022

Aim:

The present study aims to evaluate oral health knowledge and habits of children with visual impairment by comparison with their sighted counterparts and also evaluates parental knowledge and involvement in children’s oral hygiene routines.

Methods:

This observational and transversal study included the participation of 68 children (34 were visually impaired and 34 were sighted), from seven schools from Lisbon. The participants with visual impairment were age and gender-matched with their sighted counterparts to minimize variations in the analysis. In all, 52.9% of children were male, with average age of 11.15 (±3.413) years [6; 18]. The children and parents completed one survey each. Children were submitted to an oral examination to evaluate oral health.

Results:

Participants with visual impairment showed a non-significant increase in the decayed, missing, and filled teeth index (dmft), gingival, and oral hygiene indexes. Both groups’ gingival state was mostly classified as excellent, and oral hygiene was mainly classified as excellent/good. More children with visual impairment (85.7%) needed help with teeth brushing ( p = .046) and were more likely to miss dentist check-ups more often ( p = .025). Also, sighted children and their parents demonstrated more knowledge about oral health.

Conclusion:

Children with visual impairment and their parents showed less favorable results, justifying the need to promote oral health education to this demographic.
Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium
Authors: He Tongrong , d’Uscio Livius V , Sun Ruohan , Santhanam Anantha Vijay R , Katusic Zvonimir S
Published: June 2022

Cerebrovascular effects of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inactivation have not been systematically studied. In the present study we employed cultured human brain microvascular endothelial cells (BMECs), BACE1-knockout (BACE1−/−) mice and conditional (tamoxifen-induced) endothelium-specific BACE1-knockout (eBACE1−/−) mice to determine effect of BACE1 inhibition on expression and function of endothelial nitric oxide synthase (eNOS). Deletion of BACE1 caused upregulation of eNOS and glypican-1 (GPC1) in human BMECs treated with BACE1-siRNA, and cerebral microvessels of male BACE1−/− mice and male eBACE1−/− mice. In addition, BACE1siRNA treatment increased NO production in human BMECs. These effects appeared to be independent of amyloid β-peptide production. Furthermore, adenoviral-mediated overexpression of BACE1 in human BMECs down-regulated GPC1 and eNOS. Treatment of human BMECs with GPC1siRNA suppressed mRNA and protein levels of eNOS. In basilar arteries of male eBACE1−/− mice, endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to NO donor, DEA-NONOate, were not affected, consistent with unchanged expression of eNOS and phosphorylation of eNOS at Ser1177 in large cerebral arteries. In aggregate, our findings suggest that under physiological conditions, inactivation of endothelial BACE1 increases expression of eNOS in cerebral microvessels but not in large brain arteries. This effect appears to be mediated by increased GPC1 expression.
Micro Bias and Macro Prejudice in the Teaching of Marketing
Authors: Benton Raymond
Published: June 2022

It is often stated that the goal of the marketing system is the satisfaction of consumer needs, wants, and desires as consumers themselves define and express them. The marketing concept places marketing and the marketer between the producer and consumer as a facilitator in accomplishing the goal of the marketing system. This article argues that marketing educators must adopt a variety of alternative perspectives in their courses if they are to satisfy the spirit of the marketing concept. The nature of critical thought is outlined and contrasted with traditional thought. A number of critical perspectives on the marketing economy are presented and contrasted with the traditional perspective. Possible readings are suggested and summarized. Explanations are discussed as to why each of the alternatives ought to be part of the marketing curriculum if the goal of the marketing system is as stated above. The author's personal experience in integrating the various perspectives in a one-semester consumer behavior course are reviewed.
Cultural adaptation of the Italian version of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Event (PRO-CTCAE®)
Authors: Caminiti Caterina , Bryce Jane , Riva Silvia , Ng Diane , Diodati Francesca , Iezzi Elisa , Sparavigna Lucia , Novello Silvia , Porta Camillo , Del Mastro Lucia , Procopio Giuseppe , Cinieri Saverio , Falzetta Amalia , Calabrò Fabio , Lorusso Vito , Cogoni Alessio Aligi , Tortora Giampaolo , Maruzzo Marco , Passalacqua Rodolfo , Cognetti Francesco , Adamo Vincenzo , Capelletto Enrica , Ferrari Alessandra , Bagnalasta Michela , Bassi Maurizio , Nicelli Annalisa , De Persis Davide , D’Acunti Alessia , Iannelli (patient) Elisabetta , Perrone Francesco , Mitchell Sandra A.
Published: June 2022

Introduction:

US National Cancer Institute’s (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients.

Methods:

All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135).

Results:

Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94).

Discussion:

Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.
Real-time jerk-minimization trajectory planning of robotic arm based on polynomial curve optimization
Authors: Wu Guanglei , Zhang Sida
Published: June 2022

This paper deals with the jerk-minimization trajectory planning of robotic arms, in order to meet the increasing demands of the practical tasks that require fast motion planning of highly dynamic real-time movements for the task execution, by means of polynomial curve-based trajectory design. By solving a constrained quadratic optimization problem, the trajectory planning is optimized by minimizing the jerk of the robot end-effector. Experimental pick-and-place operations are carried out in comparison with the trajectory design without optimization and non-uniform rational B-spline (NURBS) curve, respectively, from which the results show the trajectory optimization is applicable in real-time trajectory planning. Both the numerical simulation and experimental implementations validate the presented approach of optimizing trajectory planning and show the effectiveness.
Public pedagogies in post-literate cultures
Authors: Graham Phil , Dugmore Harry
Published: June 2022

In this paper we present a perspective on normalisation that turns on public pedagogies; that is, on ambient, ever-present systems of mediated experience that consciously teach ways of seeing, evaluating, acting, and reacting. Our perspective is further focused by theories of literacy and utopianism. It takes the view that we are in, or at least fast moving towards, post-literate cultures for which instructions to achieve political utopias are grounded in the devices of narrative mnemonics. We demonstrate our perspective using negative discourse analysis and show how narrative elements from extremist manifestos get normalised through the mediations and remediations of mainstream politicians, and through print and broadcast journalism, greatly aided at every stage by the volatile environments of digital media.
Adaptive robust control of a class of motor servo system with dead zone based on neural network and extended state observer
Authors: Xu Chenchen , Hu Jian
Published: June 2022

In the actual motor servo system, dead zone, saturation, and hysteresis are some of the most common nonlinear characteristics. Among them, the dead zone is the most serious to the system performance. This article focuses on the nonlinearity of the dead zone, and uses back-propagation neural network to smoothly and continuously compensate the dead zone. Considering that larger disturbances will slow down the convergence of the neural network and become easier to diverge, it is necessary to use extended state observer to share part of the disturbance observations. Based on this, a robust adaptive controller is designed for a class of motor system with torque control to achieve high-precision motion control. Using feedforward cancelation technology, extended state observer and back-propagation neural network are combined with robust adaptive controller to achieve high-performance control of motor system. By using Lyapunov theorem, the adaptive laws of parameters and weights of neural networks are derived. The global robustness of the control strategy is guaranteed by the proper feedback robust law. In addition, the controller guarantees the tracking performance under various uncertainties in theory, which is of great significance to the high-precision control of the motion system. The high performance of the control strategy is verified by simulation and experiment.
Not like riding a bike: How public libraries facilitate older people’s digital inclusion during the Covid-19 pandemic
Authors: Casselden Biddy
Published: June 2022

The UK digital divide, whereby sections of society have limited use of digital technology, results in unequal access to information, knowledge, goods and services. The Covid-19 pandemic has exacerbated the push to a digital world, and this has challenged people who suffer digital exclusion, including older people, who are more likely to lack digital skills and understanding. Public libraries play a key role in tackling digital exclusion, providing digital skills training and support, and access to equipment and Wi-Fi thereby enhancing the social inclusion of marginalised groups. During the Covid-19 pandemic innovative solutions were piloted to help tackle digital exclusion and social isolation despite closure of face-to-face library interventions, particularly during lockdowns. This article explores evaluation of the Housing Plus Pilot, providing remote digital skills training and support to older people living in sheltered housing in Newcastle upon Tyne during 2021, delivered through partnership between Your Homes Newcastle, and Newcastle City Libraries. A qualitative case study approach examined a small sample of older people’s perceptions regarding the success of the pilot, and their digital literacy before and after training using semi-structured interviews via telephone. Findings showed that the pilot enabled older people to gain the necessary digital knowledge and skills required to boost confidence in becoming digitally literate citizens. Tackling digital fears and enabling them to reinforce learning through the provision of their own tablet, and free access to Wi-Fi in their sheltered housing provided a springboard for digital behaviour change. Use of a social setting in sheltered housing not only kept older people safe during socially distanced times, but also provided a supportive environment in which to learn and practice skills, together with a step-by-step training approach that focussed on the individual, which was wellsuited to this demographic.
Design and synthesis of high-performance poly(amide-imide) for multifunctional electromagnetic interference shielding films
Authors: Zhuang Changlong , Wang Yanbin , Chang Chengbi , Fan Zicheng , Hou Shuhan , Zhou Chen , Dong Hao , Xia Leier , Luo Zhonglin , Wang Biaobing
Published: June 2022

The exploration of flexible, transparent, anti-corrosion and thermally stable electromagnetic interference (EMI) shielding materials is still a huge challenge and urgently demanded in the civil and military fields. Herein, two novel high-performance poly (amide-imide)s (PAIs) were designed and used to fabricate sandwich structure EMI shielding films through simple layer-by-layer casting method. Combining advantages of PAI and silver nanowires (Ag NWs), PAI/Ag NWs composite films showed a shielding effectiveness (SE) of 35 dB and simultaneously possessed an optical transmittance of beyond 80%. More encouragingly, the composite films remained more than 92% EMI SE with random deformations (>5000 times). Furthermore, benefitting from the excellent properties of PAI matrix and sandwich structure of EMI shielding films, the EMI SE was almost unchanged even when they were exposed to air for 30 min at 160°C. On the other hand, the PAI/Ag NWs composite films still exhibited EMI SE of more than 30 dB when they were dipped into aqueous solution for 1 h by varying pH values from 2 to 13. These results demonstrated that PAI and Ag NWs was a good combination to prepare EMI shielding materials with excellent comprehensive performances.
How Did the COVID-19 Restrictions Impact People Living With Dementia and Their Informal Carers Within Community and Residential Aged Care Settings in Australia? A Qualitative Study
Authors: Lion Katarzyna Małgorzata , Moyle Wendy , Cations Monica , Day Sally , Pu Lihui , Murfield Jenny , Gabbay Mark , Giebel Clarissa
Published: June 2022

The aim of this study was to explore how formal social support changed after implementation of the COVID-19 public health measures and how these restrictions affected people living with dementia and their informal carers in Australia. Sixteen informal carers and two people living with dementia were interviewed between August and November 2020. Participants were asked about their experiences of the pandemic and the impact that the restrictions had on their lives and care. Thematic analysis identified four overarching themes describing (a) prepandemic limitations of the aged care system, (b) the aged care system’s response to the COVID-19 restrictions, (c) changes affecting informal carers, and (d) the challenges faced by people living with dementia. The findings highlighted the challenges faced by the Australian aged care system before the pandemic and the additional burden placed on informal carers who supported people living with dementia across residential and home settings during the pandemic.
Prevailing Wage Repeal, Highway Construction Costs, and Bid Competition in Kentucky: A Difference-in-Differences and Fixed Effects Analysis
Authors: Duncan Kevin C. , Gigstad Jill L. , Manzo Frank P.
Published: June 2022

Data for over 2,000 highway pavement projects, constructed between 2014 and 2020, are used to examine the effect of Kentucky’s prevailing wage repeal in 2017 on relative bid costs and bid competition for state and federally funded work. Other than Davis-Bacon and Disadvantaged Business Enterprise policies for federal projects, and prevailing wage requirements on state-funded work prior to 2017, all highway construction in Kentucky is built to the same standard. A difference-in-differences and fixed effects analysis fails to find statistically significant differences in bid costs and competition between federal and state projects before and after repeal. Competition on pavement projects in Kentucky is very low compared to other states. Consequently, the impact of increased competition on bid costs is very high. Policies increasing competition in Kentucky would be more effective in reducing costs than prevailing wage repeal.
Faith or path? Profiling the motivations of multilingual Chinese as a foreign language teachers using Q methodology
Authors: Lu Xiuchuan , Geng Zhi
Published: June 2022

As a topic of rising interest, language teacher motivation has been studied through various lenses and across different contexts over recent years. Yet, relatively scant attention has been paid to Chinese language teachers teaching overseas. Using Q methodology and supplementary interview data, this study investigated the motivational profiles of multilingual Chinese as a foreign language (CFL) teachers who teach abroad. An analysis informed by the Factors Influencing Teaching Choice (FIT-Choice) model identified four types of career choice motivation: ‘self-devotion and social contribution’, ‘personal utility’, ‘personal interest+’, and ‘personal pursuit and immigration path’. The results show that teachers with a strong sense of national pride and social responsibility chose the career mainly for social contribution. They shared with teachers driven by personal interest, a positive attitude and a strong commitment to the career. Teachers driven by personal utility and teachers pursuing diverse life experiences or permanent residence were more likely to choose to teach Chinese as a last resort, which potentially inhibited their determination and commitment to the job. The study further explores the complexity of teachers’ career choice motivation by investigating the interaction between the identified types. The discussion of these findings contributes to a better understanding of the subjectivity of multilingual CFL teachers and provides insights into Chinese teachers’ professional development and the sustainability of international Chinese education.
Cross-media usage and explorative digital music consumption: An optimum stimulation-level perspective and evidence from China
Authors: Ryu Sunghan , Dutta Shantanu , Chen Baizhu
Published: June 2022

Based on a theoretical perspective of the optimum stimulation level (OSL), we investigate how the cross-media usage (multi-device and multi-app usage) of individual users influences their exploration of new music in a music-streaming platform. We also examine whether gender moderates the link between cross-media usage and new music exploration behavior. We analyze survey responses from 1116 college students in China, and our findings show a significant and positive effect of multi-device usage on new music exploration. By contrast, multi-app usage does not have any statistically significant effect. The results also indicate that being a woman positively moderates the relationship between multi-app usage and new music exploration behavior. Our study contributes to the understanding of exploratory user behavior in a new media context by linking the OSL theory to digital music consumption.
Compressive and bending behavior of foam-filled Kevlar fiber composite sandwich panel with novel lozenge core: A numerical and experimental study
Authors: Nosratbakhsh Mohammad , Rostamiyan Yasser , Maddah Soroush
Published: June 2022

The present research has addressed the flexural and compressive strength of Kevlar fiber composite sandwich panels with novel lattice core, experimentally and numerically. The composite sandwich panels and corrugated cores have been made using the vacuum-assisted resin transfer molding method. Afterward, compressive and three-point bending loads were applied to the composite sandwich panels to determine mechanical performance during structural deformation. Scanning electron microscopy has been conducted on the specimens to evaluate the Kevlar-fiber distribution. In order to evaluate the experimental results, the corresponding testing process has been numerically simulated through finite element analysis. It has been figured out that the simulated model can predict the force–displacement response of the considered sandwich panels under bending and compressive loads. Finally, the effect of polyurethane foam on the composite sandwich panel's mechanical strength and energy absorption capacity has been investigated.
Influence of jet-to-crossflow pressure ratio and combustor width on performance of a hydrogen fueled scramjet
Authors: Aziz Sarfaraz , Chowdhury Md. Navid , Shingh Shanto Kumar , Ali Mohammad
Published: June 2022

In the development of hypersonic propulsion systems, efficient mixing of gaseous jets in supersonic cross-stream has been facing formidable challenges for over a decade. This paper presents a numerical analysis of a non-reacting scramjet (Supersonic Combustion Ramjet) combustor flow field by solving the two-dimensional Reynolds-Averaged Navier-Stokes (RANS) equations coupled with the Menter SST k-ω model. The focus of this study is to investigate the effects of jet-to-crossflow pressure ratio and combustor width on various performance parameters such as mixing efficiency, total pressure recovery, and mass-flux-weighted Mach number. Accordingly, gaseous jets of hydrogen are injected from two opposite walls on finite parallel streams of air with rearward-facing step configurations. The jet-to-crossflow pressure ratio is varied as 4.5, 9.0, 13.5, and 18.0 while the combustor widths of 40, 50, and 60 mm are considered for the present investigation. Particular emphasis is placed on the utilization of internal shock waves to enhance the combustor performance in lieu of the conventional methods of using shock generators. The insight physics of fuel-air mixing under the influence of internal shocks is also explained. The results reveal that proper shock utilization can improve the overall performance and reduce the overall dimension of the combustion chamber. For the jet-to-crossflow pressure ratio of 4.5, around 10% higher mixing efficiency and 15% greater total pressure recovery are achieved without choking the internal flow when the combustor width is reduced from 60 to 40 mm.