bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of shifted gate stack engineering over negative capacitance tunnel field effect transistor (NCTFET)
Authors: Singh Amandeep , Sinha Sanjeet Kumar , Chander Sweta
Published: September 2022

In this work, the performance of negative capacitance field effect transistor is closely investigated with different source material to improvise the transfer characteristics and sub-threshold swing. Tunnel Field Effect Transistor (TFET) being a strong competitor of conventional MOSFET for low power applications has its abilities to pull down Subthreshold Swing (SS) below fundamental limit but it has its own limitations of lower ION current and existence of ambipolar region for lower VGS voltage range. This ambipolar behavior is strongly seen in case of silicon source NCTFET but when source material is replaced with Germanium, a heterojunction is formed at source channel junction, and because of that, improvised result is obtained in terms of steeper subthreshold slope and ION/IOFF ratio. This work compares the transfer characteristics obtained in case of Si-Source and Ge-Source Negative Capacitance Tunnel Field Effect Transistor (NCTFET). The results obtained indicates that heterojunction NCTFET gives a subthreshold swing of 56.6 mV dec−1 and enhances ION/IOFF ratio to 0.24 × 108 in magnitude.
Optimization of the synthesis of silver nanoparticles using the leaf extract of Ocimum sanctum and evaluation of their antioxidant potential
Authors: Melkamu Zaza , Jeyaramraja P R , Paulos Taddesse
Published: September 2022

This work investigates the green synthesis of silver nanoparticles (AgNPs) utilizing the aqueous leaf extract of Ocimum sanctum L. A change in colour to dark brown from yellow and an absorption maximum at 460 nm provided evidence for the synthesis of AgNPs. Several reaction conditions namely leaf extract volume, AgNO3 concentration and duration of incubation were optimized. Maximum synthesis of AgNPs could be achieved with 1 ml of 5% aqueous leaf extract, 1 mM AgNO3 and 2.5 h incubation period. DPPH (2, 2—diphenyl − 1 - picrylhydrazyl) assay revealed that AgNPs are better than the leaf extract in terms of antioxidant potential. These results strongly recommend the application of green-synthesized AgNPs as effective antioxidants against oxidative stresses associated with degenerative diseases. Characterization of AgNPs were then carried out using certain methods namely as x-ray diffraction (XRD) measurement, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). XRD study confirmed the synthesis of face-centered cubic-shaped AgNPs that are of crystalline nature. The mean particle size of the synthesized AgNPs computed employing the Debye–Scherrer formula, was 22 nm. FTIR study demonstrated that the AgNPs consisted of certain functional groups of O. sanctum which might have helped in reducing AgNO3 and capping AgNPs. SEM images showed the synthesis of AgNPs of various shapes viz. globular, cubical and flaky. The scattered AgNPs were found to have a size close to 20 nm, which roughly matches with the XRD analysis of the current study.
The American Journal of Epidemiology and Social Epidemiology: Past and Future
Authors: Kawachi Ichiro
Published: September 2022

Historically, the American Journal of Epidemiology (AJE) has played an important role in the development of social epidemiology as a field. To mark the centennial of the Journal, we invited commentaries from 3 sets of authors in which we asked them to reflect on the role of the AJE in advancing our understanding of the social determinants of population health and health disparities. Drs. Lisa Berkman, Mauricio Avendano, and Emilie Courtin discuss the promises and pitfalls of using experimental data (from both randomized trials and natural policy experiments) to interrogate the causal connection between social determinants and population health outcomes. Drs. Julie Palmer, Yvette Crozier, and Lynn Rosenberg look back on the first 25 years of the Black Women’s Health Study and the contributions of that study to our understanding of racial disparities in health. Drs. Luisa Borrell and Natalie Crawford review the AJE’s contributions to the definition and use of race and ethnicity in epidemiologic research and make recommendations for strengthening diversity and inclusion in the profession. A common thread that emerges across the invited essays is the AJE’s commitment to publishing articles that engage in critical self-reflection of the discipline.
The Transitional Decade
Authors: Schryer Stephen
Published: September 2022

Nicky Marsh’s Credit Culture: The Politics of Money in the American Novel of the 1970s (2020), Michael Trask’s Ideal Minds: Raising Consciousness in the Antisocial Seventies (2020), and Andrew Strombeck’s DIY on the Lower East Side: Books, Buildings, and Art after the 1975 Fiscal Crisis (2020) challenge literary historical paradigms that treat the 1970s as a transitional decade. For all three writers, the transitional nature of the 1970s is precisely the feature that needs to be explored and theorized. In each text, the neoliberal 1980s are on the horizon, visible in the rise of financialization (Marsh), in the popularization of neoidealist models of the self (Trask), and in the mid-1970s fiscal crisis of New York (Strombeck). Yet rather than presenting neoliberalism as the inevitable result of these shifts, Marsh, Trask, and Strombeck explore foreclosed historical possibilities arising from the collapse of the Fordist economy, theorizing the 1970s as a moment of possibility when history could have followed different tracks.The three authors theorize the 1970s as a moment of possibility when history could have followed different tracks. 1970s cultural production, they argue, alternately traced these lost pathways and helped usher in the privatized 1980s.
Targeting novel sites in DNA gyrase for development of anti-microbials
Authors: Salman Mohd , Sharma Priyanka , Kumar Mukesh , Ethayathulla A S , Kaur Punit
Published: September 2022

Antimicrobial resistance in bacteria poses major challenges in selection of the therapeutic regime for managing the infectious disease. There is currently an upsurge in the appearance of multiple drug resistance in bacterial pathogens and a decline in the discovery of novel antibiotics. DNA gyrase is an attractive target used for antibiotic discovery due to its vital role in bacterial DNA replication and segregation in addition to its absence in mammalian organisms. Despite the presence of successful antibiotics targeting this enzyme, there is a need to bypass the resistance against this validated drug target. Hence, drug development in DNA gyrase is a highly active research area. In addition to the conventional binding sites for the novobiocin and fluoroquinolone antibiotics, several novel sites are being exploited for drug discovery. The binding sites for novel bacterial type II topoisomerase inhibitor (NBTI), simocyclinone, YacG, Thiophene and CcdB are structurally and biochemically validated active sites, which inhibit the supercoiling activity of topoisomerases. The novel chemical moieties with varied scaffolds have been identified to target DNA gyrase. Amongst them, the NBTI constitutes the most advanced DNA gyrase inhibitor which are in phase III trial of drug development.

The present review aims to classify the novel binding sites other than the conventional novobiocin and quinolone binding pocket to bypass the resistance due to mutations in the DNA gyrase enzyme. These sites can be exploited for the identification of new scaffolds for the development of novel antibacterial compounds.
DRviaSPCN: a software package for drug repurposing in cancer via a subpathway crosstalk network
Authors: Wu Jiashuo , Li Xiangmei , Wang Qian , Han Junwei
Published: September 2022

Drug repurposing is an approach used to discover new indications for existing drugs. Recently, several computational approaches have been developed for drug repurposing in cancer. Nevertheless, no approaches have reported a systematic analysis of pathway crosstalk. Pathway crosstalk, which refers to the phenomenon of interaction or cooperation between pathways, is a critical aspect of tumor pathways that allows cancer cells to survive and acquire resistance to drug therapy. Here, we innovatively developed a system biology R-based software package, DRviaSPCN, to repurpose drugs for cancer via a subpathway (SP) crosstalk network. This package provides a novel approach to prioritize cancer candidate drugs by considering drug-induced SPs and their crosstalk effects. The operation modes mainly include construction of the SP network and calculation of the centrality scores of SPs to reflect the influence of SP crosstalk, calculation of enrichment scores of drug- and disease-induced dysfunctional SPs and weighted them by the centrality scores of SPs, evaluation of the drug–disease reverse association at the weighted SP level, identification of cancer candidate drugs and visualization of the results. Its capabilities enable DRviaSPCN to find cancer candidate drugs, which will complement the recent tools which did not consider crosstalk among pathways/SPs. DRviaSPCN may help to facilitate the development of drug discovery.

Availability and implementation

The package is implemented in R and available under GPL-2 license from the CRAN website (https://CRAN.R-project.org/package=DRviaSPCN).

Supplementary information

Supplementary data are available at Bioinformatics online.
Midfrontal theta dynamics index the monitoring of postural stability
Authors: Stokkermans Mitchel , Solis-Escalante Teodoro , Cohen Michael X , Weerdesteyn Vivian
Published: September 2022

Stepping is a common strategy to recover postural stability and maintain upright balance. Postural perturbations have been linked to neuroelectrical markers such as the N1 potential and theta frequency dynamics. Here, we investigated the role of cortical midfrontal theta dynamics of balance monitoring, driven by balance perturbations at different initial standing postures. We recorded electroencephalography, electromyography, and motion tracking of human participants while they stood on a platform that delivered a range of forward and backward whole-body balance perturbations. The participants’ postural threat was manipulated prior to the balance perturbation by instructing them to lean forward or backward while keeping their feet-in-place in response to the perturbation. We hypothesized that midfrontal theta dynamics index the engagement of a behavioral monitoring system and, therefore, that perturbation-induced theta power would be modulated by the initial leaning posture and perturbation intensity. Targeted spatial filtering in combination with mixed-effects modeling confirmed our hypothesis and revealed distinct modulations of theta power according to postural threat. Our results provide novel evidence that midfrontal theta dynamics subserve action monitoring of human postural balance. Understanding of cortical mechanisms of balance control is crucial for studying balance impairments related to aging and neurological conditions (e.g. stroke).
Sex-specific life-history strategies among immature jumping spiders: Differences in body parameters and behavior
Authors: Mezőfi László , Markó Viktor , Taranyi Dóra Ágnes , Markó Gábor
Published: September 2022

Selection forces often generate sex-specific differences in various traits closely related to fitness. While in adult spiders (Araneae), sexes often differ in coloration, body size, antipredator, or foraging behavior, such sex-related differences are less pronounced among immatures. However, sex-specific life-history strategies may also be adaptive for immatures. Thus, we hypothesized that among spiders, immature individuals show different life-history strategies that are expressed as sex-specific differences in body parameters and behavioral features, and also in their relationships. We used immature individuals of a protandrous jumping spider, Carrhotus xanthogramma, and examined sex-related differences. The results showed that males have higher mass and larger prosoma than females. Males were more active and more risk tolerant than females. Male activity increased with time, and larger males tended to capture the prey faster than small ones, while females showed no such patterns. However, females reacted to the threatening abiotic stimuli more with the increasing number of test sessions. In both males and females, individuals with better body conditions tended to be more risk averse. Spiders showed no sex-specific differences in interindividual behavioral consistency and in intraindividual behavioral variation in the measured behavioral traits. Finally, we also found evidence for behavioral syndromes (i.e., correlation between different behaviors), where in males, only the activity correlated with the risk-taking behavior, but in females, all the measured behavioral traits were involved. The present study demonstrates that C. xanthogramma sexes follow different life-history strategies even before attaining maturity.
Plateau pikas near roads are bold and silent when facing a potential predator
Authors: Zhu Bicheng , Qu Jiapeng , Cui Jianguo
Published: September 2022

Human disturbance, particularly road traffic, is one of the greatest threats to wildlife. Considering the association between alerting behavior and the survival of animals, it is important to study the effects of road traffic on alerting behavior of wildlife. Previous studies assessing the short-term impact of road traffic on alerting behavior of wildlife have focused on vigilance distances. However, studies on the use of alarm calls are scarce, and it is unclear whether such behavioral responses change after repeated exposure to road traffic. We assessed the alerting behavior of plateau pikas (Ochotona curzoniae) who were near or far from roads when facing a potential predator. We found that pikas near roads exhibited shorter vigilance and tolerance distances, and produced fewer alarm calls than those relatively far away from roads. Furthermore, both vigilance and tolerance distances of plateau pikas were significantly positively correlated with the distance from the burrow to the road. Road traffic reduced antipredator responses and shaped alerting behavior; that is, pikas near roads were bolder and more silent compared to those far away from roads. Our findings suggest that increasing urbanization will have corresponding effects on animal behavior, which may have significant fitness effects in the future.
Predictors of enteral tube dependence in pediatric esophageal atresia
Authors: Yasuda Jessica L , Taslitsky Gabriela N , Staffa Steven J , Ngo Peter D , Meisner Jay , Mohammed Somala , Hamilton Thomas , Zendejas Benjamin , Manfredi Michael A
Published: September 2022

Children with esophageal atresia (EA) may require enteral tube feedings in infancy and a subset experience ongoing feeding difficulties and enteral tube dependence. Predictors of enteral tube dependence have never been systematically explored in this population. We hypothesized that enteral tube dependence is multifactorial in nature, with likely important contributions from anastomotic stricture. Cross-sectional clinical, feeding, and endoscopic data were extracted from a prospectively collected database of endoscopies performed in EA patients between August 2019 and August 2021 at an international referral center for EA management. Clinical factors known or hypothesized to contribute to esophageal dysphagia, oropharyngeal dysphagia, or other difficulties in meeting caloric needs were incorporated into regression models for statistical analysis. Significant predictors of enteral tube dependence were statistically identified. Three-hundred thirty children with EA were eligible for analysis. Ninety-seven were dependent on enteral tube feeds. Younger age, lower weight Z scores, long gap atresia, neurodevelopmental risk factor(s), significant cardiac disease, vocal fold movement impairment, and smaller esophageal anastomotic diameter were significantly associated with enteral tube dependence in univariate analyses; only weight Z scores, vocal fold movement impairment, and anastomotic diameter retained significance in a multivariable logistic regression model. In the current study, anastomotic stricture is the only potentially modifiable significant predictor of enteral tube dependence that is identified.
Sex and age as predictors of health-related quality of life change in Phase II cardiac rehabilitation
Authors: Jellestad Lena , Auschra Bianca , Zuccarella-Hackl Claudia , Princip Mary , von Känel Roland , Euler Sebastian , Hermann Matthias
Published: September 2022

Aims

Cardiac rehabilitation (CR) not only improves cardiovascular outcomes, but also health-related quality of life (HRQOL). Unfortunately, CR is still underutilized, especially among women and older patients. Aim of this study was to highlight age- and sex-specific effects of inpatient CR on HRQOL.

Methods and results

From 2012 to 2018, 18 459 patients were prospectively assessed in six Swiss CR clinics. Of these, we retrospectively analysed a final sample of 8286 patients with a mean (standard deviation) age of 67.8 (11.3) in men and 72.2 (11.3) in women. HRQOL was measured at CR entry and discharge. In multivariable analyses, sex- and age-specific changes in HRQOL throughout CR were estimated, adjusting for baseline HRQOL and clinical characteristics. Participants of both sexes improved significantly (P < 0.001) in all domains of HRQOL during CR. Women reported significantly lower social (P < 0.001) and emotional (P < 0.001) HRQOL than men at CR entry. Female sex predicted greater improvement in social (F = 19.63, P < 0.001), emotional (F = 27.814, P < 0.001), and physical HRQOL (F = 20.473, P < 0.001). In a subgroup of n = 2632 elderly patients (>75 years), female sex predicted greater changes in emotional (F = 15.738, P < 0.001) and physical (F = 6.295, P = 0.012), but not in social HRQOL.

Conclusion

Women report poorer HRQOL at CR entry compared with men, but in turn particularly benefit from CR in this regard. Our results indicate that sex- and age-specific needs of patients should be considered.
A bHLH transcription factor, SlbHLH96, promotes drought tolerance in tomato
Authors: Liang Yunfei , Ma Fang , Li Boyu , Guo Cong , Hu Tixu , Zhang Mingke , Liang Yan , Zhu Jianhua , Zhan Xiangqiang
Published: September 2022

Drought stress caused by water deficit reduces plant productivity in many regions of the world. In plants, basic helix–loop–helix (bHLH) transcription factors regulate a wide range of cellular activities related to growth, development and stress response; however, the role of tomato SlbHLHs in drought stress responses remains elusive. Here, we used reverse genetics approaches to reveal the function of SlbHLH96, which is induced by drought and abscisic acid (ABA) treatment. We found that SlbHLH96 functions as a positive regulator of drought tolerance in tomato. Overexpression of SlbHLH96 in tomato improves drought tolerance by stimulating the expression of genes encoding antioxidants, ABA signaling molecules and stress-related proteins. In contrast, silencing of SlbHLH96 in tomato reduces drought tolerance. SlbHLH96 physically interacts with an ethylene-responsive factor, SlERF4, and silencing of SlERF4 in tomato also decreases drought tolerance. Furthermore, SlbHLH96 can repress the expression of the ABA catabolic gene, SlCYP707A2, through direct binding to its promoter. Our results uncover a novel mechanism of SlbHLH96-mediated drought tolerance in tomato plants, which can be exploited for breeding drought-resilient crops.
Evidence and consensus on technical aspects of embryo transfer
Authors: D’Angelo Arianna , Panayotidis Costas , Alteri Alessandra , Mcheik Saria , Veleva Zdravka
Published: September 2022

BACKGROUND

Ultrasound-guided embryo transfer (US-GET) is a widely performed procedure, but standards for the best practice are not available.

OBJECTIVE AND RATIONALE

This document aims to provide an overview of technical aspects of US-GET after considering the published data and including the preparation for the embryo transfer (ET) procedure, the actual procedure, the post-procedure care, associated pathologies, complications and risks, quality assurance and practitioners’ performance.

SEARCH METHODS

A literature search for evidence on key aspects of the ET procedure was carried out from database inception to November 2021. Selected papers (n = 359) relevant to the topic were analysed by the authors. The following key points were considered in the papers: whether ultrasound (US) practice standards were explained, to what extent the ET technique was described and whether complications or incidents and how to prevent such events were reported. In the end, 89 papers could be used to support the recommendations in this document, which focused on transabdominal US-GET.

OUTCOMES

The relevant papers found in the literature search were included in the current document and described according to the topic in three main sections: requirements and preparations prior to ET, the ET procedure and training and competence for ET. Recommendations are provided on preparations prior to ET, equipment and materials, ET technique, possible risks and complications, training and competence. Specific aspects of the laboratory procedures are covered, in particular the different loading techniques and their potential impact on the final outcomes. Potential future developments and research priorities regarding the ET technique are also outlined.

LIMITATIONS, REASONS FOR CAUTION

Many topics were not covered in the literature review and some recommendations were based on expert opinions and are not necessarily evidence based.

WIDER IMPLICATIONS

ET is the last procedural step in an ART treatment and is a crucial step towards achieving a pregnancy and live birth. The current paper set out to bring together the recent developments considering all aspects of ET, especially emphasizing US quality imaging. There are still many questions needing answers, and these can be subject of future research.

STUDY FUNDING/COMPETING INTEREST(S)

No funding. A.D.A. has received royalties from CRC Press and personal honorarium from Cook, Ferring and Cooper Surgical. The other co-authors have no conflicts of interest to declare that are relevant to the content of this article.
Country data on AMR in Brazil in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome
Authors: Torumkuney Didem , Nijhara Puja , Beltrame Cristiana Ossaille , Baisch Elisama Queiroz , Ferreira Ricardo Macarini
Published: September 2022

Background

Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action.

Objectives

To review the situation with respect to AMR in Brazil and initiatives addressing it. Identifying areas where more information is required will provide a call to action to minimize any further rises in AMR within Brazil and to improve patient outcomes.

Methods

National initiatives to address AMR, antibiotic use and prescribing in Brazil, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infections (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines for CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) commonly used locally were also reviewed, along with local antibiotic availability.

Conclusions

In Brazil there have been some initiatives addressing AMR such as the National Action Plan for AMR, established in 2018. Antibiotic consumption in Brazil is high but a ban on over-the-counter sales of antibiotics has led to a decrease in consumption. Local antibiotic susceptibility testing needs to be increased and the Survey of Antibiotic Resistance (SOAR) study in Brazil will provide useful data for pathogens causing CA-RTIs. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Brazil, could make guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical outcomes for patients.
Country data on AMR in Mexico in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome
Authors: Torumkuney Didem , de la Torre Carlos , Langfeld Karen , Lopez-Turrent Norma Patricia , Ossaille Beltrame Cristiana
Published: September 2022

Background

Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action.

Objectives

To review AMR in Mexico and initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rises in AMR and to improve patient outcomes.

Methods

National AMR initiatives in Mexico, antibiotic use and prescribing, and availability of susceptibility data, particularly the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used in Mexico for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) were also reviewed, along with local antibiotic availability. Insights from a local clinician were sought to contextualize this information.

Conclusions

The Mexican national AMR strategy was published in 2018. This comprised similar objectives to the Global Action Plan from the World Health Assembly (2015) and was compulsory, requiring full compliance from members of the National Health System. Historically, antibiotic consumption in Mexico has been high, however, between 2000 and 2015, consumption fell, in sharp contrast to the majority of countries. Mexico lacks a national surveillance network for AMR, however there are several ongoing global surveillance studies providing local antibiotic susceptibility data. International and local antibiotic prescribing guidelines for CA-RTIs are used. A more standardized inclusive approach in developing local guidelines, using up-to-date local surveillance data of isolates from community-acquired infections, could make guideline use more locally relevant. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development in Mexico and improve patient outcomes.
Early Life Antibiotic Prescription for Upper Respiratory Tract Infection Is Associated With Higher Antibiotic Use in Childhood
Authors: Samtani Bhavna , Gray Natasha , Omand Jessica , Keown-Stoneman Charles , Aglipay Mary , Birken Catherine , Maguire Jonathon
Published: September 2022

Background

Antibiotic prescription for uncomplicated upper respiratory tract infection (URTI) in children is not recommended but remains common. The primary objective was to evaluate the relationship between antibiotic prescription for URTI prior to age 2 and antibiotic prescription for URTI after age 2. It was hypothesized that antibiotic prescription for URTI in early childhood may increase the risk of antibiotic use for subsequent URTIs. The secondary objective was to investigate whether this relationship was different for acute otitis media (AOM), for which antibiotics may be indicated.

Methods

A prospective cohort study was conducted between December 2008 and March 2016 at 9 primary care practices in Toronto, Canada. Healthy children aged 0–5 years that met TARGet Kids! cohort eligibility criteria were included if they had at least one sick visit prior to age 2 and least one sick visit after age 2. Generalized Estimating Equation (GEE) models were used to evaluate this relationship while considering within-subject correlation.

Results

Of 2380 participants followed for a mean duration of 4.6 years, children who received an antibiotic prescription for URTI prior to age 2 had higher odds of receiving an antibiotic prescription for URTI in later childhood (adjusted odds ratio: 1.39; 95% confidence interval: 1.19 to 1.63; P < .001). This relationship did not appear to be different for AOM compared to non-AOM URTI.

Conclusion

Antibiotic prescription for URTI before age 2 was associated with antibiotic prescription for URTI in later childhood. Reducing early life antibiotic prescription for URTI may be associated with reduction in antibiotic prescription for subsequent URTIs.
An Argumentation-Based Approach for Goal Reasoning and Explanations Generation
Authors: Morveli-Espinoza Mariela , Nieves Juan Carlos , Tacla Cesar Augusto , Jasinski Henrique M R
Published: September 2022

Explainable Artificial Intelligence systems, including intelligent agents, are expected to explain their internal decisions, behaviors and reasoning that produce their choices to the humans (or to other systems) with which they interact. Given this context, the aim of this article is to introduce a practical reasoning agent framework that supports generation of explanations about the goals the agent committed to. Firstly, we present an argumentation-based formalization for supporting goal reasoning. This is based on the belief-based goal processing model proposed by Castelfranchi and Paglieri, which is a more granular and refined model than the Beliefs–Desires–Intentions model. We focus on the dynamics of goals since they are desires until they become intentions, including the conditions under which a goal can be cancelled. We use formal argumentation reasoning to support the passage of the goals from their initial state until their final state. Secondly, in order that agents based on the proposed formalization be able to generate explanations about the goals they decided to commit to, we endow them with a mechanism for generating both complete and partial explanations. Finally, we use a scenario of rescue robots in order to illustrate the performance of our proposal, for which a simulator was developed to support the agents goal reasoning.
Building (of) the international community: a history of the Peace Palace through transnational gifts and local bureaucracy
Authors: Aalberts Tanja , Stolk Sofia
Published: September 2022

The Peace Palace in The Hague is more than a mere venue where international law is practiced. Initiated after the 1899 Peace Conference it provided a material home for the emergent international community and as such, we argue, helped to sing this community into existence. This article traces the process of materialising the grand international ideal of ‘peace through justice’ by shedding light on its bureaucratic backstage of transnational diplomacy. Taking a ritual perspective on gift-giving as a way to constitute relationships, we analyse how three sets of gifts were crucial to (the) building (of) the emergent international community: finding a proper site (as a gift from the Dutch government), securing Andrew Carnegie’s financial gift, and collecting materials and artworks donated by the States as gifts to the Palace. We examine how each of these arrangements involved a complex web of public and private transnational actors, temporalities, and bickering over nitty gritty details as the conditions of possibility for giving and receiving gifts, and constituting the international community.
Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging
Authors: Zhang Yiyuan , Zheng Yandong , Wang Si , Fan Yanling , Ye Yanxia , Jing Yaobin , Liu Zunpeng , Yang Shanshan , Xiong Muzhao , Yang Kuan , Hu Jinghao , Che Shanshan , Chu Qun , Song Moshi , Liu Guang-Hui , Zhang Weiqi , Ma Shuai , Qu Jing
Published: September 2022

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Realistic compact stars in conformal teleparallel gravity
Authors: Nashed G G L , Bamba Kazuharu
Published: September 2022

We explore an interior solution of a physically symmetric vierbein with two unknown functions in conformal teleparallel gravity. The field equations can be described in a closed system for a particular form of the metric potentials and an appropriate anisotropic function. As a result, we find a new set of configurations consistent with observed pulsars. In particular, the boundary conditions for the interior spacetime are used for the Schwarzschild spacetime to constrain the conformal field with a unit value through the surface of a compact object. Furthermore, we apply the present model to the pulsar 4U 1608−52 with an approximate radius R = 9.52 ± 0.15 km and mass $M= 1.74 \pm 0.14\, \mathrm{M}_{\odot }$. To analyze the stability, we also study the causality conditions and the adiabatic index by assuming the Tolman–Oppenheimer–Volkoff equation, an adiabatic index, and the static state. Moreover, the consistency of the model under consideration with other pulsars is investigated.
The unseen cloud: a survey of vaping practices and the acquisition of vaping products within the UK
Authors: Sund L J , Wood D M , Archer J R H , Blundell M S , Dargan P I
Published: September 2022

Background

Vaping of cannabinoid-based products and informal acquisition of vaping products were associated with the outbreak of E-cigarette or vaping associated lung injury (EVALI) in the USA. Current prevalence of cannabinoid-based vaping within the UK is not known and literature regarding the acquisition of vaping products is limited.

Aim

To estimate the prevalence of nicotine-based, nicotine-free and cannabinoid-based product vaping within the UK and to determine where vaping products are acquired.

Design and methods

A voluntary online survey of individuals aged 16 and over within the UK was conducted using a convenience sample. Data were collected on respondent demographics, smoking/vaping history and acquisition of e-liquids/products.

Results

A total of 2478 responses were included. Median age 45 years (interquartile range 35–57). Prevalence of current vaping of nicotine-based e-liquids, nicotine-free e-liquids and cannabinoid-based products was 14.4%, 11.2% and 5.49%, respectively. Current nicotine-based and nicotine-free vaping was most prevalent in 25–34 years olds (22.4% and 19.2% of respondents). Current cannabinoid-based vaping was most prevalent in 16–24 years olds. The most common ‘ever’ used cannabinoid-based products were cannabidiol oil/cannabigerol oil and cannabis leaves (4.8%). Specialist vaping stores were the most common source of ‘ever’ acquisition for all products. 36.8% and 40.5% of respondents who had ever vaped nicotine-based and nicotine-free e-liquids reported prior acquisition from informal sources.

Conclusion

This survey reported a higher prevalence of current cannabinoid-based vaping within the UK (5.5%) than previously reported in the USA (2.0%). In addition to the informal acquisition of vaping products as demonstrated within the survey, these results highlight potential underestimation of the risk of EVALI within the UK.
Titanium membrane layered between fluvastatin-loaded poly (lactic-co-glycolic) acid for guided bone regeneration
Authors: Furuhashi Akihiro , Rakhmatia Yunia Dwi , Ayukawa Yasunori , Koyano Kiyoshi
Published: September 2022

The aim of this study was to investigate titanium membranes (TMs) layered between poly (lactic-co-glycolic acid) (PLGA) containing fluvastatin (FS) for use in guided bone regeneration. Membranes consisting of PLGA, FS-containing PLGA (PLGA–FS), TM layered between PLGA (TM–PLGA) and TM layered between FS-containing PLGA (TM–PLGA–FS) were prepared, and their mechanical and chemical properties were evaluated. The TM groups showed statistically significant differences, in terms of tensile strength and elastic modulus, when compared to the PLGA groups. The release of FS was demonstrated to be higher in the TM–PLGA–FS group than the PLGA–FS group after Day 14. The effect of membrane implantation on the calvaria of Wistar rats was measured using micro-computed tomography (micro-CT) and morphometrical analyses, as well as histological observations. At 4 weeks, the TM–PLGA–FS and TM–PLGA groups were found to have lower bone mineral density but higher bone formation, when compared to the control and PLGA groups. At 8 weeks, the use of TM–PLGA–FS membranes significantly enhanced bone formation in the calvaria model, compared to the other groups. These results suggest that a TM layered between PLGA containing FS potentially enhances bone formation, thus showing good potential as a GBR membrane.
Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior
Authors: Sousa Ana Beatriz , Águas Artur P , Barbosa Mário A , Barbosa Judite N
Published: September 2022

Successful wound healing is a process that has three overlying phases: inflammatory, proliferative and remodeling. Chronic wounds are characterized by a perpetuated inflammation that inhibits the proliferative and remodeling phases and impairs the wound healing. Macrophages are key modulators of the wound healing process. Initially, they are responsible for the wound cleaning and for the phagocytosis of pathogens and afterwards they lead to the resolution of the inflammatory response and they express growth factors important for angiogenesis and cytokines and growth factors needed for cell proliferation and deposition of extracellular matrix. The phenotype of the macrophage changes gradually throughout the healing process from the initial M1 pro-inflammatory phenotype characteristic of the acute response to the M2 pro-regenerative phenotype that allows an accurate tissue repair. In chronic wounds, M1 pro-inflammatory macrophages persist and impair tissue repair. As such, immunomodulatory biomaterials arise as promising solutions to accelerate the wound healing process. In this review, we discuss the importance of macrophages and their polarization throughout the different phases of wound healing; macrophage dysfunction in chronic wounds and the use of immunomodulatory biomaterials to overcome the critical problem of chronic wounds—the continued inflammatory phase that impairs healing.
Abstract 15 Safety of DUOC-01, Intrathecal Cord Blood-Derived Cellular Therapy, as an Adjunct to Allogeneic Cord Blood Transplantation in Children with Inherited Metabolic Diseases
Authors: Sun Jessica , Baker Jennifer , Cheatham Lynn , Millette Drew , Prasad Vinod , Kurtzberg Joanne
Published: September 2022

Introduction

Unrelated donor umbilical cord blood transplantation (CBT) improves function and extends life in children with certain inherited metabolic diseases (IMDs); however, progressive neurologic decline often occurs during the few months post-CBT prior to donor engraftment in the brain, causing residual, irreversible impairments. We previously described donor engraftment in the brain after CBT and developed DUOC-01, a monocyte-derived CB cell product, to attempt to accelerate donor cell delivery to the brain.

Objective

The objective of this study was to determine manufacturing feasibility and safety of intrathecal DUOC-01 in a phase I study in children with IMDs undergoing CBT after myeloablative cytoreduction (busulfan/cyclophosphamide/anti-thymocyte globulin).

Methods

DUOC-01 was manufactured in adherent cell culture in a GMP lab over 21 days with a target dose of ≤100 × 105 cells. When cell dose permitted, 80% of the CB unit was used for transplant and 20% of the same unit was used to manufacture DUOC-01. Otherwise, DUOC-01 was manufactured from a unique CB unit. On day ≥+28 post-CBT, if there was evidence of hematopoietic engraftment without severe graft versus host disease or morbidity, DUOC-01 cells were harvested and administered intrathecally. Safety was monitored via neurologic exams, neuroimaging, and CSF studies.

Results

Forty patients (aged 0-15 years) underwent CBT, 37 engrafted with donor cells. Median infused total nucleated cell count was 6.5 × 107/kg (range 2.9-33.1 × 107/kg); median time to neutrophil engraftment was 20 days (range 13-46 days). Ten patients did not receive DUOC-01 cells for the following reasons: engraftment failure (3), transplant-related morbidity (4), and low manufacturing yield (3). Thirty patients received 0.2-100 × 105 DUOC-01 cells intrathecally for a median of 31 days (range 27-77 days) post-CBT (19 with the same CB donor and 11 with a unique CB donor). Two patients developed transient fever and hypotension hours after unique-donor DUOC-01, consistent with an inflammatory response. Hydrocortisone (HC) was added to the final formulation, and post-validation, seven additional patients received unique-donor DUOC-01+HC without incident. No other DUOC-01-related serious adverse events occurred.

Discussion

DUOC-01 is a CB-derived product intended to accelerate donor cell delivery to the brain of children with IMDs undergoing CBT. Intrathecal DUOC-01 administration is well-tolerated post-CBT from the same donor and, with the addition of HC, also from a unique donor. Escalating DUOC doses are being tested for safety and exploration of potential efficacy in a phase Ia trial of adults with multiple sclerosis.
Abstract 17 Comparison of Different Support Materials and Cryoprotectants for Amniotic Membrane Cryopreservation
Authors: Ogliari Karolyn , Grudzinski Patrícia , Immig Mônica , Halon Maria , Loth Fabrízio , Tovo Monique , da Silva Camila , Beckenkamp Liziane
Published: September 2022

Introduction

The amniotic membrane (AM) is a thin membrane derived from the placenta, rich in stem cells and structural components that stimulate tissue regeneration. This tissue has emerged as a biological dressing for several clinical applications. Many preservation techniques have been proposed for AM; however, searching for a method capable of preserving their physical and biological properties remains challenging.

Objective

This work investigated different ways to support the AM in packing, as well as two different cryoprotectants to preserve its histological, cytological, and biological characteristics.

Methods

Human placentas were processed for AM isolation and stored under various conditions: gauze (G) and petrolatum gauze (PG) were evaluated as support materials for the AM, while DMSO and glycerol were analyzed as cryoprotectants for both materials. In addition, after selecting the best support material, two forms of product presentation were also explored: flat fragment (FF) and roll (R). All protocols were stored in liquid nitrogen for at least 2 weeks. After this period, tissue was thawed, and structural integrity, cellular viability, and secretome analysis were performed.

Results

Cellular viability with PG was significantly reduced compared with fresh AM (Fresh: 63.6% ± 11.8%; PG+DMSO: 37.2% ± 17.9%; PG+glycerol: 23.2% ± 18.9%) (Figure 1A). Regarding gauze presentation, no difference in cell viability was found between cryoprotectants in the flat fragment groups (FF+DMSO: 53.4% ± 20.2% and FF+Glycerol: 55.5% ± 15.8%) (Figure 1B). As for the roll groups, cell viability was significantly better for DMSO (R+DMSO: 63.9% ± 11.8% and R+Glycerol: 37.1% ± 19.5V) (Figure 1B). Structural integrity evaluated by tissue immunofluorescence and picrosirius confirmed that the extracellular matrix components, such as laminin (Figure 1D), fibronectin (Figure 1E), and collagen (Figure 1F and 1G), were preserved with both cryoprotectants. Likewise, this protocol conserved progenitor/stem cells, assessed by the CD117 marker (Fresh: 25.4% ± 8.7%, DMSO:18.1% ± 9.5%, and Glycerol: 23.1% ± 11.7%) (Figure 1C). Secretome analysis showed a slight reduction of the proteins secreted by cryopreserved AM compared with fresh AM, although the difference was not significant (Figure 1H). Essential proteins involved in tissue regeneration (fibronectin, laminins, collagens, cadherins, and cytokeratins) and immune and antimicrobial control (PTX3, TMP1, SOD, lysozyme C, and immunoglobulins) could be detected from both AM (Figure 1I).

Discussion

PG support was harmful to cell viability. DMSO exhibited better results in cell viability and biological functions regardless of tissue presentation and cryopreservation.