bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Driving Vehicles—an Ethical Overview
Authors: Hansson Sven Ove , Belin Matts-Åke , Lundgren Björn
Published: August 2021

The introduction of self-driving vehicles gives rise to a large number of ethical issues that go beyond the common, extremely narrow, focus on improbable dilemma-like scenarios. This article provides a broad overview of realistic ethical issues related to self-driving vehicles. Some of the major topics covered are as follows: Strong opinions for and against driverless cars may give rise to severe social and political conflicts. A low tolerance for accidents caused by driverless vehicles may delay the introduction of driverless systems that would substantially reduce the risks. Trade-offs will arise between safety and other requirement on the road traffic system. Over-reliance on the swift collision-avoiding reactions of self-driving vehicles can induce people to take dangerous actions, such as stepping out in front of a car, relying on its fast braking. Children travelling alone can violate safety instructions such as the use of seatbelts. Digital information about routes and destinations can be used to convey commercial and political messages to car users. If fast passage can be bought, then socio-economic segregation of road traffic may result. Terrorists and other criminals can hack into a vehicle and make it crash. They can also use self-driving vehicles for instance to carry bombs to their designed places of detonation or to wreak havoc on a country’s road system.
Deconstructing Job Insecurity: Do its Qualitative and Quantitative Dimensions Add Up?
Authors: Urbanaviciute Ieva , Lazauskaite-Zabielske Jurgita , De Witte Hans
Published: August 2021

Despite substantial interest in job insecurity as a severe workplace stressor, the way in which its qualitative and quantitative dimensions co-occur is not fully understood. As a result, the variety of their combinations and potentially differential effects that they produce remain underexplored. The current study aimed to address this gap in two ways. First, we hypothesized that quantitative job insecurity would manifest in a cumulated form along with qualitative job insecurity but not vice versa. Second, we aimed to test whether different combinations of quantitative and qualitative job insecurity differentially reflect in employees’ occupational characteristics and health and well-being outcomes.

Latent profile analyses were conducted on two different samples of employees (N = 1077 andN = 608). The findings from both samples supported a three-profile solution of qualitative and quantitative job insecurity resulting in the balanced low, balanced high, and qualitative job insecurity dominant profiles. As expected, the probability of temporary and part-time employment was the highest in the balanced high (i.e., cumulated) job insecurity profile. Moreover, both the balanced high and the qualitative job insecurity dominant profiles were linked to significantly lower mental health and well-being than the low job insecurity profile, suggesting that substantially detrimental effects may occur even if experiencing qualitative job insecurity only.
UAV Formation Obstacle Avoidance Control Algorithm Based on Improved Artificial Potential Field and Consensus
Authors: Wang Ning , Dai Jiyang , Ying Jin
Published: August 2021

Aiming at the problem of UAV formation's obstacle avoidance and the consensus of position and velocity in a 3D obstacle environment, a novel distributed obstacle avoidance control algorithm for cooperative formation based on the improved artificial potential field (IAPF) and consensus theory is proposed in this paper. First, the particle model of the UAV and the dynamic model of the second-order system are established, and the topological structure of the communication network of the system is described with the knowledge of graph theory. Second, the attractive potential field function containing the coordination gains factor, the repulsive potential field function containing the influence factor of the repulsive force and the planning angle, and the potential field function between the UAVs containing the communication weight are defined. Then, the variables of position and velocity in the consensus protocol are improved by the reference vector of the formation center and the expected velocity, respectively, and a new formation obstacle avoidance control protocol is designed by combining the IAPF and the theory of consensus. Finally, the Lyapunov function is used to prove the stable convergence of the algorithm. The simulation results show that this method can not only prevent the UAV from colliding with each other while avoiding static and dynamic obstacles but also enable the UAV to quickly restore the expected formation and achieve the consensus of the relative distance, relative height, and velocity.
The Verification of Nanosatellites Solar Panels Automatic Deployment in Microgravity Conditions
Authors: Abdellatif Akram , Ali Ali H. , El-sayed Mohamed E. , Elhusseiny Nermine M. , Mabrouk Youmna , Fathy Youssef M.
Published: August 2021

The solar panels installed on a CubeSat are considered the main energy source of a nanosatellites. The deployment mechanism of a solar panel must be analyzed and tested extensively. Any suggested solar panel design should present a low vibrating free spinning deployment mechanism. This paper examines various types of solar panels to reach a conclusion of the efficient design when deployed on a 1U or 2U unit. However, calculations, analysis, simulations do not always give an extensive picture of how the satellite shall behave during deployment. Thus, testing in a microgravity environment gives a more accurate answer of how the satellite shall behave. In our work, various solar panels mechanisms are developed and eventually tested in microgravity. The first accordion structure for a 1U structure is tested in a microgravity environment through a parabolic flight with the National Research Council Falcon 20 aircraft. The results are recorded and analyzed to optimize the next design. The second design is based on a drag-sail mechanism for a 2U structure. The design is improved upon the first experiment results for the next parabolic flight. The simulated amount of power generated in orbit is also a main factor in our evaluation.
COVID 19 pandemic: Effect on management of patients with breast cancer; single center retrospective cohort study
Authors: Mooghal Mehwish , Javaid Rana Hassan , Khan Wajiha , Muneeb Muhammad , Khan Waseem Ahmad , Ahmad Asrar , Barohi Lal Bux , Rahim Kamran , Tahseen Hina , Gul Amna
Published: August 2021

ABSTRACT

Background:

(SARS-COV-2) infection, led to a pandemic affecting many countries, resulting in hospitals diverting most of their resources to fight the pandemic. Breast cancer, already a healthcare dilemma, is also affected in this scenario. Our aim was to find out the impact of COVID-19 on presentation of breast cancer stage and its effects on overall onco-surgical management.

Methods:

This cohort single-centered retrospective review was carried out at our hospital, over a period of 18 months. Females with known breast cancer were included in the study. Data was collected on performas by a single researcher. Effect of COVID pandemic on presentation stage and its impact on overall management was studied. SPSS 23.0 used for data analysis. A 95% CI was used. Descriptive statistics were presented as range/means. Categorical data was analyzed by Fisher exact test, t-test was applied to numerical data, p value ≤ 0.05 was considered significant.

Results:

Out of 87 patients presenting with suspicious lump, 69 who had malignancy on histo-pathology were included in study. Twelve out of 69 were COVID positive. Sixty patients presented with advanced stage (≥stage 2b) out of which 21 underwent upstaging of disease due to delay in presentation/management. We found that 9 out of 12 (majority) Covid positive patients had disease upstaging. Overall main reason for delay in presentation was found to be unawareness of disease.

Conclusion:

We concluded that COVID-19 pandemic had no impact on presentation delay, breast cancer management/treatment and disease upstaging as compared to figures available for our population before the pandemic. However, our study showed significant correlation between disease upstaging and COVID status. This led us to reconsider our preformed protocols for COVID positive breast cancer patients. Our results can be used by future researchers to investigate if COVID itself can contributes in patho-physiology of upstaging in breast cancer or not.

Highlights
Introduction to the Standard Model and Beyond
Authors: Raby Stuart
Published: August 2021

The Standard Model of particle physics is an amazingly successful theory describing the fundamental particles and forces of nature. This text, written for a two-semester graduate course on the Standard Model, develops a practical understanding of the theoretical concepts it's built upon, to prepare students to enter research. The author takes a historical approach to demonstrate to students the process of discovery which is often overlooked in other textbooks, presenting quantum field theory and symmetries as the necessary tools for describing and understanding the Standard Model. He develops these tools using a basic understanding of quantum mechanics and classical field theory, such as Maxwell's electrodynamics, before discussing the important role that Noether's theorem and conserved charges play in the theory. Worked examples feature throughout the text, while homework exercises are included for the first five parts, with solutions available online for instructors. Inspired by the author's own teaching experience, suggestions for independent research topics have been provided for the second-half of the course, which students can then present to the rest of the class.
Anaphoric binding in Modern Standard Arabic: A phase-based analysis
Authors: Al-Raba'a Basem Ibrahim Malawi
Published: August 2021

This article explores the distribution of Arabic reflexive and reciprocal anaphors in various structures as well as the syntactic environments in which such anaphors are (in)admissible. In particular, it examines the binding domains for reflexives and reciprocals and focuses for the most part on the asymmetries between these two types of anaphors in possessive DPs and PPs. It will be shown that the binding facts are better captured by reducing binding domains to phases, that DPs and PPs constitute a phase only when containing a possessive phrase, and that a reflexive and a reciprocal behave differently in such possessive structures in that the latter, unlike the former, undergoes overt movement. Accordingly, it will be argued that reflexive possessives are ungrammatical because they are left unbound in their DP/PP phase, while reciprocal possessives are grammatical since multiple copies of the distributor are created during the derivation due to movement, allowing it to seek an antecedent in the higher vP, its phasal binding domain. For this to hold, Principle A should apply cyclically at the end of each phase; that is, before the complement of the phase head is spelled out.
New Middle Ordovician hyoliths from the Ossa Morena Zone, southwestern Spain
Authors: Gutiérrez-Marco Juan Carlos , Marek Ladislav , Malinky John M.
Published: August 2021

The record of Middle Ordovician (Oretanian, ca. Darriwilian 2) hyolithids from the Ossa Morena Zone of the Iberian Massif in southwestern Spain is increased with the recognition ofRobardetlites sevillanusn. gen. n. sp.,Andalucilites parvulusn. gen. n. sp.,Pauxillites desolatusn. sp.,Leolites malinkyiMarek and Gutiérrez-Marco n. sp., andCavernolitessp. in that region.Andalucilitesn. gen. andRobardetlitesn. gen. are endemic whereas the other genera are known from coeval strata in the Barrandian region in central Europe, France, and Morocco, giving this assemblage a decidedly “Mediterranean province” character. The discovery ofPauxillites,Leolites, andCavernolitesin Iberia extends their geographic ranges to that region, andLeolitesfrom this area extends its stratigraphic range downward, making its occurrence in Iberia the oldest known for that genus.

UUID:http://zoobank.org/f5b29223-6dac-4c7e-8851-551e634da667
Travelling wave fronts of Lotka-Volterra reaction-diffusion system in the weak competition case
Authors: Wang Yang , Li Hongliang , Li Xiong
Published: August 2021

This paper is concerned with spreading phenomena of the classical two-species Lotka-Volterra reaction-diffusion system in the weak competition case. More precisely, some new sufficient conditions on the linear or nonlinear speed selection of the minimal wave speed of travelling wave fronts, which connect one half-positive equilibrium and one positive equilibrium, have been given via constructing types of super-sub solutions. Moreover, these conditions for the linear or nonlinear determinacy are quite different from that of the minimal wave speeds of travelling wave fronts connecting other equilibria of Lotka-Volterra competition model. In addition, based on the weighted energy method, we give the global exponential stability of such solutions with large speed $c$. Specially, when the competition rate exerted on one species converges to zero, then for any $c>c_0$, where $c_0$ is the critical speed, the travelling wave front with the speed $c$ is globally exponentially stable.
Variations in the levels of acute-phase proteins and lactoferrin in serum and milk during bovine subclinical mastitis
Authors: Raj Aarsha , Kulangara Vinodkumar , Vareed Tresamol P. , Melepat Deepa P. , Chattothayil Latha , Chullipparambil Sunanda
Published: August 2021

Variations in the levels of acute phase proteins and lactoferrin in serum and milk for diagnosis of subclinical mastitis in dairy cows are described in this research paper. Milking animals from two organized dairy farms in Kerala, India, were screened by California Mastitis Test (CMT), Electrical Conductivity test (EC) and Somatic Cell Count (SCC) test to identify animals affected with sub clinical mastitis (SCM). The concentrations of acute phase proteins (APP) Haptoglobin (Hp), C- reactive protein (CRP), Albumin, Lactoferrin (Lf) and α- 1 acid glycoprotein (AGP) in milk and Hp, Albumin, Serum Amyloid A (SAA) and CRP in the serum of 40 normal cows and 40 cows affected with sub clinical mastitis were assessed. Solid phase ELISA was employed for assessment of all parameters except the albumin levels, for which spectrophotometry was used. The values of Hp in milk; and SAA, AGP and Lf in serum, were significantly elevated in the group with sub clinical mastitis. Such variations were found to be independent of the specific bacterial organism causing the disease. These results show that significant variations exist in the levels of acute phase proteins Hp, AGP and Lf in milk, and SAA in serum of animals affected with subclinical bovine mastitis that are not affected by specific bacterial etiology.
The nature and significance of the Hindu Divine Mother in embodied thealogical perspective
Authors: Burley Mikel
Published: August 2021

The Hindu Divine Mother is revered by millions of religious practitioners in India and elsewhere, yet this goddess rarely receives attention in Western philosophy of religion. Focusing especially (though not exclusively) on her form as Kālī, this article utilizes sources from Hindu goddess traditions to explicate her contrasting characteristics, which include benign maternality and martial aggression. By adapting an embodied theological (or thealogical) approach derived from feminist discourse, the intelligibility of worshipping such a goddess is expounded; connections are delineated between the conceptualizing of divinity as radically ambivalent or multivalent and the lived experience of inhabiting an often hostile world.
The New Modernization
Authors: Sklar Richard L.
Published: August 2021

In the latter 1940s, a growing number of American intellectuals, including scholars in various academic disciplines, were attracted to the study of Africa by two powerful incentives. First, African nationalism created a new horizon for the advancement of democracy, the twentieth century's preeminent political ideal. Second, many intellectuals were anxious to reconstruct the prevailing theories of society so that they would fairly represent the aspirations and problems of people everywhere on earth. From this perspective, due regard for the contributions of Africa was deemed to be a scientific, as well as a moral, imperative. These goals, democracy and universalism, were embraced and combined by the theorists of modernization.
‘Because it's easier to kill that way’: Dehumanizing epithets, militarized subjectivity, and American necropolitics
Authors: McIntosh Janet
Published: August 2021

This article examines the blunt conceptual instrument of dehumanizing American military terms for the enemy in the context of the Vietnam War and the Global War on Terror. I examine language that dehumanizes American service members themselves, who are semiotically framed as expendable. Next, I explore the essentialist, semi-propositional qualities of derogatory epithets for the enemy and the affectively charged, deadly stances they encourage. I examine how generic references to the enemy during training make totalizing claims that risk encompassing civilians in their typifications. And I show that, in the context of war, the instability of derogatory epithets can manifest itself when the servicemember is confronted with the behavioral idiosyncrasies and personal vulnerabilities of actual ‘enemies’ on the ground. The putative folk wisdom found in generic references to the enemy can thus fall apart when confronted with countervailing experience; in such cases, service members may shift stance by renouncing military epithets. (Military language, epithets, slurs, generics, othering, dehumanization, necropolitics)*
The social (and cultural, and syntactic, and semantic) life of generics
Authors: Mannheim Bruce
Published: August 2021

Recent work in linguistics, philosophy, and psychology suggests that the distinction between generic and specific (singular) reference is foundational to concept formation, and hence of special interest to social scientists. Generics provide the first-language learner with external evidence of the integrity of a word/concept cluster, partially filling in the scaffolding of concepts. As such, they arereplicators,critical to the transmission of concepts across populations and across time. Generics are tacitly normative. As they refer to the constitutive properties of a concept rather than to its object, they tell us what—in a given social setting—a proper instance of the concept should look like. Generics sustain and reproduce social stereotypes, including—and perhaps especially—ethnoracial, class, and gender stereotypes. (Generics, conceptual formation, ethnography, tokenization, materiality)*
INDIVIDUAL DIFFERENCES IN HOW LANGUAGE LEARNERS PURSUE GOALS
Authors: Teimouri Yasser , Papi Mostafa , Tahmouresi Somayeh
Published: August 2021

In two studies, we examined two functional dimensions of L2 learners’ self-regulation toward their motivational goals: assessment and locomotion. The assessment constitutes the aspect of self-regulation concerned with critically evaluating the relative quality of L2 states and goals and the means to achieve them. The locomotion mode constitutes the aspect of self-regulation concerned with uninterrupted movement from state to state toward L2 goals. We developed two scales to measure L2 self-regulatory modes. We also examined how L2 learners’ regulatory modes were associated with their emotional experiences, motivation, and language proficiency. Psychometric work attested to the reliability and validity of the two scales. Moreover, regression analyses revealed that each L2 self-regulatory mode has distinct emotional, motivational, and linguistic emphases. Finally, cluster analyses suggested that both L2 self-regulatory modes should work together for optimal L2 learning outcomes.
Four-site skinfolds thickness percentiles of schoolchildren and adolescents in Turkey
Authors: Soylu Meltem , Şensoy Nazlı , Doğan İsmet , Doğan Nurhan , Mazıcıoğlu M Mümtaz , Öztürk Ahmet
Published: August 2021

Objective:

The primary purpose of the current study was to establish Turkish smoothed centile charts and Lambda, Mu, Sigma (LMS) tables for four-site skinfold thickness based on a population-based sample, and secondary purpose was to elaborate a reference for the percentage of body fat.

Design:

A cross-sectional and descriptive study was conducted between January and May 2017. Triceps, biceps and subscapular, suprailiac skinfold thicknesses were measured using Holtain skinfold caliper. Age- and gender-specific percentile values were determined with the LMS method, and body fat percentage was calculated using the Westrate and Deurenberg equation.

Setting:

Afyonkarahisar province in Turkey.

Participants:

The current study was conducted on 4565, 6–18-year-old students.

Results:

The triceps, biceps and subscapular skinfolds of the girls were higher than the boys. From the age of seven, the sum of four skinfold thicknesses of the girls was more than those of the boys. This difference became more evident after the age of 12. Although fat percentages of girls showed a fluctuating change, it decreased with the age in boys. Westrate and Deurenberg equation fat percentages of girls until adolescence were lower than boys, but increased after 12 years of age and exceeded that of boys.

Conclusions:

The current study has provided sex- and age-specific reference values for skinfold thickness and has shown that obesity in girls is higher than in boys in schoolchildren in Afyonkarahisar. The current study has also shown that skinfold thickness measurements are a valuable tool for screening obesity in children.
Prevalence and correlates of US adult public opinion on restricting junk food advertising to children on social media: 2020 Health Information National Trends Survey
Authors: Korn Ariella R , Blake Kelly D , D’Angelo Heather , Reedy Jill , Oh April
Published: August 2021

Objective:

To describe US adults’ levels of support, neutrality and opposition to restricting junk food advertising to children on social media and explore associations with socio-demographic and health-related characteristics.

Design:

In 2020–2021, we used cross-sectional data from the National Cancer Institute’s 2020 Health Information National Trends Survey to estimate the prevalence of opinions towards advertising restrictions and correlates of neutrality and opposition using weighted multivariable logistic regression.

Setting:

United States.

Participants:

Adults aged 18+ years.

Results:

Among the analytic sample (n 2852), 54 % of adults were neutral or opposed to junk food advertising restrictions on social media. The odds of being neutral or opposed were higher among Non-Hispanic Black adults (v. non-Hispanic White; OR: 2·03 (95 % CI 1·26, 3·26)); those completing some college (OR: 1·68 (95 % CI 1·20, 2·34)) or high school or less (OR: 2·62 (95 % CI 1·74, 3·96)) (v. those with a college degree); those who were overweight (v. normal weight; OR: 1·42 (95 % CI: 1·05, 1·93)) and those reporting a moderate (OR: 1·45 (95 % CI 1·13, 1·88)) or conservative (OR: 1·71 (95 % CI 1·24, 2·35)) political viewpoint (v. liberal). Having strong (v. weaker) weight and diet-related cancer beliefs was associated with 53 % lower odds of being neutral or opposed to advertising restrictions (OR: 0·47 (95 % CI 0·36, 0·61)).

Conclusions:

The current study identified subgroups of US adults for whom targeted communication strategies may increase support for policies to improve children’s food environment.
Geological Records of Coseismic Shear Localization Along the Yangsan Fault, Korea
Authors: Gu Dohee , Han Raehee , Woo Sangwoo
Published: August 2021

We conducted outcrop‐to‐nanoscale structural observations on a principal slip zone (PSZ) of the Yangsan fault, a major strike‐slip fault in southeast Korea, and some high‐velocity rotary shear tests on the PSZ gouges to understand shear localization and physico‐chemical processes in the PSZ during earthquakes. At the fault outcrop, the PSZ appears 1–2 cm thick. At smaller scales, the PSZ is subdivided into Units 1 to 4 based on their microstructures. Microscopic observations confirmed the shear localization in Units 1 (20–500 μm in thickness) and 3 (0.8–3 mm in thickness). Further localization was observed in several μm‐thick shear bands. Various structural and mineralogical features that recorded physico‐chemical processes in slip zones were found in the PSZ, including gouge fluidization structures relevant to thermal pressurization, solidified frictional melt of clay‐rich gouge, and mineralogical changes by frictional heating‐induced illitization. The gouge melting and mineralogical changes were reproduced in our experiments at 1.3 m s−1. The gouge fluidization has been observed in previous tests at seismic slip rates. Thus, the observations from the natural and experimental faults indicate that the shear localization in the PSZ was coseismic. In a cataclasite zone next to the PSZ, altered veins of pseudotachylyte were found. All these observations indicate temporal changes of the PSZ materials (e.g., formation of solidified melt, alteration of the melt into clay minerals, friction‐induced mineralogical changes). Associated with such changes, coseismic slip zone processes and dominant weakening mechanisms may also vary, even at the same location on a fault.
Specifically Tailored Action Plans Combat Heat Waves in India
Authors: Padmanaban Deepa
Published: August 2021

The frequencies of heat waves and heat-induced mortality have soared in India. Now government agencies and research organizations are developing city-specific action plans to mitigate heat impacts.
Cluster Observations of Energetic Electron Acceleration Within Earthward Reconnection Jet and Associated Magnetic Flux Rope
Authors: Vaivads A. , Khotyaintsev Yu. V. , Retinò A. , Fu H. S. , Kronberg E. A. , Daly P. W.
Published: August 2021

We study acceleration of energetic electrons in an earthward plasma jet due to magnetic reconnection in the Earth magnetotail for one case observed by Cluster. The case has been selected based on the presence of high fluxes of energetic electrons, Cluster being in the burst mode and Cluster separation being around 1,000 km that is optimal for studies of ion scale physics. We show that two characteristic acceleration mechanisms are operating during this event. First, significant acceleration is achieved inside the magnetic flux pile‐up of the jet, the acceleration mechanism being consistent with betatron acceleration. Second, strong energetic electron acceleration occurs in magnetic flux rope like structure forming in front of the magnetic flux pile‐up region. Energetic electrons inside the magnetic flux rope are accelerated predominantly in the field‐aligned direction and the acceleration can be due to Fermi acceleration in a contracting flux rope.
A Statistical Study of Low‐Energy Ion Flux Enhancements by EMIC Waves in the Inner Magnetosphere
Authors: Lee Junhyun , Kim Khan‐Hyuk , Lee Ensang
Published: August 2021

We have studied the statistical properties of low‐energy proton (H+) and helium (He+) ion flux enhancements associated with electromagnetic ion cyclotron (EMIC) waves in the inner magnetosphere using Van Allen Probes data for 2013–2017. We identified 167 low‐energy ion flux enhancements when the EMIC waves occurred in a He‐band or in a multiple band (H‐band and He‐band) with strong He‐band and weak H‐band wave activity and found that most of them occurred from the noon to the premidnight sector near the magnetic equator just inside the plasmapause. Of 167 flux enhancement events, 68 exhibited only He+ flux enhancements, and 99 exhibited both H+ and He+ flux enhancements. The EMIC wave‐associated flux enhancement events are mostly energized in the direction perpendicular to the background magnetic field. When both H+ and He+ fluxes are simultaneously enhanced, the H+ flux events have a peak energy distributed in the range of 2–100 eV, and the peak energies of the He+ flux events are distributed in the 2–600 eV range, implying that the helium ions are more energized than the protons. The peak energies of only He+ flux enhancement without H+ flux enhancement are mostly distributed in a lower energy range, 2–10 eV. The energization of H+ and He+ ions can be explained by a linear plasma flow associated with EMIC waves. We suggest that the wave‐associated linear plasma motion is a likely mechanism to explain the observations.
Histone demethylase KDM4A plays an oncogenic role in nasopharyngeal carcinoma by promoting cell migration and invasion
Authors: Zhao Jingyi , Li Bingyan , Ren Yongxia , Liang Tiansong , Wang Juan , Zhai Suna , Zhang Xiqian , Zhou Pengcheng , Zhang Xiangxian , Pan Yuanyuan , Gao Fangfang , Zhang Sulan , Li Liming , Yang Yongqiang , Deng Xiaoyu , Li Xiaole , Chen Linhui , Yang Daoke , Zheng Yingjuan
Published: August 2021

Compelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.
N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study
Authors: Beck Katherine , Arumuham Atheeshaan , Veronese Mattia , Santangelo Barbara , McGinnity Colm J. , Dunn Joel , McCutcheon Robert A. , Kaar Stephen J. , Singh Nisha , Pillinger Toby , Borgan Faith , Stone James , Jauhar Sameer , Sementa Teresa , Turkheimer Federico , Hammers Alexander , Howes Oliver D.
Published: August 2021

N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p < 0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.
Drug addiction: from bench to bedside
Authors: Cheron Julian , Kerchove d’Exaerde Alban de
Published: August 2021

Drug addiction is responsible for millions of deaths per year around the world. Still, its management as a chronic disease is shadowed by misconceptions from the general public. Indeed, drug consumers are often labelled as “weak”, “immoral” or “depraved”. Consequently, drug addiction is often perceived as an individual problem and not societal. In technical terms, drug addiction is defined as a chronic, relapsing disease resulting from sustained effects of drugs on the brain. Through a better characterisation of the cerebral circuits involved, and the long-term modifications of the brain induced by addictive drugs administrations, first, we might be able to change the way the general public see the patient who is suffering from drug addiction, and second, we might be able to find new treatments to normalise the altered brain homeostasis. In this review, we synthetise the contribution of fundamental research to the understanding drug addiction and its contribution to potential novel therapeutics. Mostly based on drug-induced modifications of synaptic plasticity and epigenetic mechanisms (and their behavioural correlates) and after demonstration of their reversibility, we tried to highlight promising therapeutics. We also underline the specific temporal dynamics and psychosocial aspects of this complex psychiatric disease adding parameters to be considered in clinical trials and paving the way to test new therapeutic venues.
High-dose methotrexate is effective for prevention of isolated CNS relapse in diffuse large B cell lymphoma
Authors: Ong Shin Yeu , de Mel Sanjay , Grigoropoulos Nicholas Francis , Chen Yunxin , Tan Yan Chin , Tan Melinda Si Yun , Ng Lawrence Cheng Kiat , Lee Yuh Shan , Phipps Colin , Goh Yeow Tee , Yong Kar Ying , Liu Xin , Chng Wee Joo , Lim Soon Thye , Nagarajan Chandramouli
Published: August 2021

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004–0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes.
Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2–host interactome
Authors: Messina Francesco , Giombini Emanuela , Montaldo Chiara , Sharma Ashish Arunkumar , Zoccoli Antonio , Sekaly Rafick-Pierre , Locatelli Franco , Zumla Alimuddin , Maeurer Markus , Capobianchi Maria R. , Lauria Francesco Nicola , Ippolito Giuseppe
Published: August 2021

In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.
Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer
Authors: Liu Dongyan , Hou Xiaonan , Wu Wangyu , Zanfagnin Valentina , Li Yunjian , Correia Cristina , Zhao Zhiyang , Zhao Chenggang , Liu Zhirong , Zhang Tao , Fang Zhiyou , Wang Hongzhi , Xu Chao , Weroha Saravut J. , Kaufmann Scott H. , Dai Haiming
Published: August 2021

We previously found that preformed complexes of BAK with antiapoptotic BCL2 proteins predict BH3 mimetic sensitivities in lymphohematopoietic cells. These complexes have not previously been examined in solid tumors or in the context of conventional anticancer drugs. Here we show the relative amount of BAK found in preformed complexes with MCL1 or BCLXL varies across ovarian cancer cell lines and patient-derived xenografts (PDXs). Cells bearing BAK/MCL1 complexes were more sensitive to paclitaxel and the MCL1 antagonist S63845. Likewise, PDX models with BAK/MCL1 complexes were more likely to respond to paclitaxel. Mechanistically, BIM induced by low paclitaxel concentrations interacted preferentially with MCL1 and displaced MCL1-bound BAK. Further studies indicated that cells with preformed BAK/MCL1 complexes were sensitive to the paclitaxel/S63845 combination, while cells without BAK/MCL1 complexes were not. Our study suggested that the assessment of BAK/MCL1 complexes might be useful for predicting response to paclitaxel alone or in combination with BH3 mimetics.
KAT2A-mediated AR translocation into nucleus promotes abiraterone-resistance in castration-resistant prostate cancer
Authors: Lu Dingheng , Song Yarong , Yu Ying , Wang Decai , Liu Bing , Chen Liang , Li Xuexiang , Li Yunxue , Cheng Lulin , Lv Fang , Zhang Pu , Xing Yifei
Published: August 2021

Abiraterone, a novel androgen synthesis inhibitor, has been approved for castration-resistant prostate cancer (CRPC) treatment. However, most patients eventually acquire resistance to this agent, and the underlying mechanisms related to this resistance remain largely unelucidated. Lysine acetyltransferase 2 A (KAT2A) has been reported to enhance transcriptional activity for certain histone or non-histone proteins through the acetylation and post-translational modification of the androgen receptor (AR). Therefore, we hypothesised that KAT2A might play a critical role in the resistance of prostate tumours to hormonal treatment. In this study, we found that KAT2A expression was increased in abiraterone-resistant prostate cancer C4-2 cells (C4-2-AbiR). Consistently, elevated expression of KAT2A was observed in patients with prostate cancer exhibiting high-grade disease or biochemical recurrence following radical prostatectomy, as well as in those with poor clinical survival outcomes. Moreover, KAT2A knockdown partially re-sensitised C4-2-AbiR cells to abiraterone, whereas KAT2A overexpression promoted abiraterone resistance in parental C4-2 cells. Consistent with this finding, KAT2A knockdown rescued abiraterone sensitivity and inhibited the proliferation of C4-2-AbiR cells in a mouse model. Mechanistically, KAT2A directly acetylated the hinge region of the AR, and induced AR translocation from the cytoplasm to the nucleus, resulting in increased transcriptional activity of the AR-targeted gene prostate specific antigen (PSA) leading to resistance to the inhibitory effect of abiraterone on proliferation. Taken together, our findings demonstrate a substantial role for KAT2A in the regulation of post-translational modifications in AR affecting CRPC development, suggesting that targeting KAT2A might be a potential strategy for CRPC treatment.
Microtubule associated protein 4 (MAP4) phosphorylation reduces cardiac microvascular density through NLRP3-related pyroptosis
Authors: Feng Yan-hai , Li Ling-fei , Zhang Qiong , Zhang Jun-hui , Huang Yao , Lv Yan-ling , Jia Jie-Zhi , Zhang Dongxia , Hu Jiong-Yu , Huang Yue-Sheng
Published: August 2021

Phosphorylation of MAP4 (p-MAP4) causes cardiac remodeling, with the cardiac microvascular endothelium being considered a vital mediator of this process. In the current study, we investigated the mechanism underlying p-MAP4 influences on cardiac microvascular density. We firstly confirmed elevated MAP4 phosphorylation in the myocardium of MAP4 knock-in (KI) mice. When compared with the corresponding control group, we detected the decreased expression of CD31, CD34, VEGFA, VEGFR2, ANG2, and TIE2 in the myocardium of MAP4 KI mice, accompanied by a reduced plasma concentration of VEGF. Moreover, we observed apoptosis and mitochondrial disruption in the cardiac microvascular endothelium of MAP4 KI animals. Consistently, we noted a decreased cardiac microvascular density, measured by CD31 and lectin staining, in MAP4 KI mice. To explore the underlying mechanism, we targeted the NLRP3-related pyroptosis and found increased expression of the corresponding proteins, including NLRP3, ASC, mature IL-1β, IL-18, and GSDMD-N in the myocardium of MAP4 KI mice. Furthermore, we utilized a MAP4 (Glu) adenovirus to mimic cellular p-MAP4. After incubating HUVECs with MAP4 (Glu) adenovirus, the angiogenic ability was inhibited, and NLRP3-related pyroptosis were significantly activated. Moreover, both cytotoxicity and PI signal were upregulated by the MAP4 (Glu) adenovirus. Finally, NLRP3 inflammasome blockage alleviated the inhibited angiogenic ability induced by MAP4 (Glu) adenovirus. These results demonstrated that p-MAP4 reduced cardiac microvascular density by activating NLRP3-related pyroptosis in both young and aged mice. We thus managed to provide clues explaining MAP4 phosphorylation-induced cardiac remodeling and enriched current knowledge regarding the role of MAP4.
Climate change modulates the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing from tropical eruptions
Authors: Aubry Thomas J. , Staunton-Sykes John , Marshall Lauren R. , Haywood Jim , Abraham Nathan Luke , Schmidt Anja
Published: August 2021

Explosive volcanic eruptions affect climate, but how climate change affects the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing remains unexplored. We combine an eruptive column model with an aerosol-climate model to show that the stratospheric aerosol optical depth perturbation from frequent moderate-magnitude tropical eruptions (e.g. Nabro 2011) will be reduced by 75% in a high-end warming scenario compared to today, a consequence of future tropopause height rise and unchanged eruptive column height. In contrast, global-mean radiative forcing, stratospheric warming and surface cooling from infrequent large-magnitude tropical eruptions (e.g. Mt. Pinatubo 1991) will be exacerbated by 30%, 52 and 15% in the future, respectively. These changes are driven by an aerosol size decrease, mainly caused by the acceleration of the Brewer-Dobson circulation, and an increase in eruptive column height. Quantifying changes in both eruptive column dynamics and aerosol lifecycle is therefore key to assessing the climate response to future eruptions.
Topological isolation of developmental regulators in mammalian genomes
Authors: Wu Hua-Jun , Landshammer Alexandro , Stamenova Elena K. , Bolondi Adriano , Kretzmer Helene , Meissner Alexander , Michor Franziska
Published: August 2021

Precise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, we found that germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings highlight the importance of developmental gene isolation through chromosomal folding structures as a mechanism to ensure their proper expression.
Mobile ions determine the luminescence yield of perovskite light-emitting diodes under pulsed operation
Authors: Kumawat Naresh Kumar , Tress Wolfgang , Gao Feng
Published: August 2021

The external quantum efficiency of perovskite light-emitting diodes (PeLEDs) has advanced quickly during the past few years. However, under pulsed operation, an operation mode which is important for display and visible light communication, the performance of PeLEDs changes a lot and requires in-depth understanding to facilitate these applications. Here, we report the response of PeLEDs under pulsed operation in the range of 10 Hz to 20 kHz. Beyond transient effects in the low frequencies, we find that for higher frequencies (>500 Hz) the transient electroluminescence intensity depends strongly on the duty cycle. This feature is much more pronounced and of different origin than that in conventional LEDs. We rationalise our experimental observations using a mathematical model and assign these features to the effect of mobile ionic charges in the perovskite. Our work also provides important implications for the operation of PeLEDs under the steady state, where accumulation of mobile ions at the interfaces could be beneficial for high electroluminescence yields but harmful for the long-term stability.
A non-printed integrated-circuit textile for wireless theranostics
Authors: Yang Yuxin , Wei Xiaofei , Zhang Nannan , Zheng Juanjuan , Chen Xing , Wen Qian , Luo Xinxin , Lee Chong-Yew , Liu Xiaohong , Zhang Xingcai , Chen Jun , Tao Changyuan , Zhang Wei , Fan Xing
Published: August 2021

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI “nurse” for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.