bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Degradation of Cortical Perineuronal Nets Reverses GABAergic Interneuron Maturation
Authors: Willis Ashleigh , Pratt Judith A. , Morris Brian J.
Published: March 2022

Perineuronal nets (PNNs) are specialised extracellular matrix structures which preferentially enwrap fast-spiking (FS) parvalbumin interneurons and have diverse roles in the cortex. PNN maturation coincides with closure of the critical period of cortical plasticity. We have previously demonstrated that BDNF accelerates interneuron development in a c-Jun-NH2-terminal kinase (JNK)–dependent manner, which may involve upstream thousand-and-one amino acid kinase 2 (TAOK2). Chondroitinase-ABC (ChABC) enzymatic digestion of PNNs reportedly reactivates ‘juvenile-like’ plasticity in the adult CNS. However, the mechanisms involved are unclear. We show that ChABC produces an immature molecular phenotype in cultured cortical neurons, corresponding to the phenotype prior to critical period closure. ChABC produced different patterns of PNN-related, GABAergic and immediate early (IE) gene expression than well-characterised modulators of mature plasticity and network activity (GABAA-R antagonist, bicuculline, and sodium-channel blocker, tetrodotoxin (TTX)). ChABC downregulated JNK activity, while this was upregulated by bicuculline. Bicuculline, but not ChABC, upregulated Bdnf expression and ERK activity. Furthermore, we found that BDNF upregulation of semaphorin-3A and IE genes was TAOK mediated. Our data suggest that ChABC heightens structural flexibility and network disinhibition, potentially contributing to ‘juvenile-like’ plasticity. The molecular phenotype appears to be distinct from heightened mature synaptic plasticity and could relate to JNK signalling. Finally, we highlight that BDNF regulation of plasticity and PNNs involves TAOK signalling.
Mental health among the general population and healthcare workers during the COVID-19 pandemic: A meta-analysis of well-being and psychological distress prevalence
Authors: Blasco-Belled Ana , Tejada-Gallardo Claudia , Fatsini-Prats Mònica , Alsinet Carles
Published: March 2022

The COVID-19 pandemic has constituted a global health crisis that has threatened the mental health of individuals worldwide. The present paper sought to systematically review and meta-analyze studies reporting the prevalence during the COVID-19 pandemic of well-being and psychological distress as defined by the dual-continua model, which includes (absence of) psychological distress and (presence of) well-being among the general population and healthcare workers. Systematic searches were conducted in various databases: PubMed, PsycINFO, Scopus, and Web of Science from inception until 6 December 2020. From a total of 158 studies (N = 880,352) included in the meta-analysis, only seven reported the prevalence of well-being. A random-effect model was used to estimate the pooled prevalence among the general population and healthcare workers on depression (25%; 31%), anxiety (27%; 31%), stress (35%; 32%), and well-being (52%; 45%), respectively. Sub-group analyses based on region, income, percentage of women, preparedness of country to respond to COVID-19, and economic vulnerabilities were conducted in order to examine sources of heterogeneity in psychological distress. Results revealed differences among the two groups and indicated that disparities in terms of preparedness to fight the pandemic can distinctly affect mental health in the general population and healthcare workers. Addressing mental health during and after a health crisis should be in the spotlight of the international and national public health agenda. Considering the protective role of well-being to minimize psychological symptoms, mental health policies during the COVID-19 should include strategies to combat the psychological consequences of the pandemic by promoting well-being practices.
Formability and surface quality of non-conventional material sheets for the manufacture of highly customized components
Authors: Formisano Antonio , Astarita Antonello , Boccarusso Luca , Garlasché Marco , Durante Massimo
Published: March 2022

In this work, incremental forming of pure niobium planar isotropic sheets was studied; in particular, two different types of test were conducted by varying the tool/sheet contact conditions, in order to understand the complex phenomena interesting this hard-to-form non-conventional material and to focus the attention on its formability and the finishing of the worked surfaces. From the tests, the formability limits were determined, the forming forces were acquired and analysed, the quality of the worked surfaces was evaluated with measures of roughness and high-magnification visual inspection, as well as the failures of the sheets were observed and interpreted. The results highlight that a proper choice of the contact conditions can avoid the occurrence of galling while preserving an optimal carrying out of the process. In any case, very good surface finishing and workability of niobium sheets, despite their brittle nature, is found when incrementally formed. As a consequence, incremental sheet forming of this non-conventional material can be considered a faisible way of manufacturing highly customized components.
Prostate cancer treatment costs increase more rapidly than for any other cancer—how to reverse the trend?
Authors: Ellinger J. , Alajati A. , Kubatka P. , Giordano F. A. , Ritter M. , Costigliola V. , Golubnitschaja O.
Published: March 2022

According to GLOBOCAN, about 1.41 million new prostate cancer (PCa) cases were registered in the year 2020 globally. The corresponding socio-economic burden is enormous. Anti-cancer mRNA-based therapy is a promising approach, the principle of which is currently applied for anti-COVID-19 vaccination, undergoing a detailed investigation in populations considering its short- and long-term effectiveness and potential side effects. Pragmatically considered, it will take years or even decades to make mRNA therapy working for any type of cancers, and if possible, for individual malignancy sub-types which are many specifically for the PCa. Actually, the costs of treating PCa are increasing more rapidly than those of any other cancer. The trend has to be reversed now, not in a couple of years. In general, two main components are making currently applied reactive (management of clinically manifested disease) PCa treatment particularly expensive. On one hand, it is rapidly increasing incidence of the disease and metastatic PCa as its subtype. To this end, rapidly increasing PCa incidence rates in young and middle-aged male sub-populations should be taken into account as a long-term contributor to the metastatic disease potentially developed later on in life. On the other hand, patient stratification to differentiate between non-metastatic PCa (no need for an extensive and costly treatment) and particularly aggressive cancer subtypes requiring personalised treatment algorithms is challenging. Considering current statistics, it becomes obvious that reactive medicine got at its limit in PCa management. Multi-professional expertise is unavoidable to create and implement anti-PCa programmes in the population. In our strategic paper, we exemplify challenging PCa management by providing detailed expert recommendations for primary (health risk assessment), secondary (prediction and prevention of metastatic disease in PCa) and tertiary (making palliative care to the management of chronic disease) care in the framework of predictive, preventive and personalised medicine.
A 2-D analytical solution to infinite conductivity fracture injection pressure transient analysis in non-Newtonian/Newtonian composite infinite reservoirs
Authors: Oluogun Mojeed Olawale , Igbokoyi Alpheus O.
Published: March 2022

Two fluid regions are usually created during either water or polymer injection into an oil reservoir for enhanced oil recovery. The two fluid regions create a composite reservoir system that requires analytical solution that can be used to evaluate the injection performance. In this study, we present a 2-D solution for non-Newtonian fluid in the inner zone coupled with infinite boundary in the outer zone using power law model. The outer zone fluid can either be Newtonian or non-Newtonian. Moreover, the mathematical model is formulated such that either zone can be with non-Newtonian power law fluid or Newtonian fluid. The infinite conductivity fractured solution obtained was compared with the ones obtained using the radial line source solution that had already been developed in the literatures, and a perfect match was obtained. An application was made to three examples that have been presented in a previous work, and satisfactory results were obtained. The dimensionless pressure drops during the early linear flow regime for all values of flow indices are the same, but with deviation during radial flow regime.
Leaflet Stresses During Full Device Simulation of Crimping to 6 mm in Transcatheter Aortic Valve Implantation, TAVI
Authors: Bressloff N. W.
Published: March 2022

Background

With continuing growth in transcatheter aortic valve implantation for the treatment of a failing aortic valve, there is increasing interest in prosthetic valve durability and the potential damage caused to leaflets by stress. Whilst most available research into the computational prediction of leaflet stresses using finite element analysis, FEA, has focussed on variations during dynamic loading, very little appears to have been reported for the impact of crimping, even though awareness of this effect is widespread. Potentially, this has been due to the difficulty of performing full model simulations of crimping to clinically meaningful diameters.

Method

A full model comprising a self-expanding frame, skirt and leaflets has been developed and crimped to a final diameter of 6 mm. A detailed description is provided of the FEA setup, emphasising the importance of the skirt definition needed to successfully crimp to this small diameter. Then, an analysis of leaflet folding and stresses is presented, particularly with respect to the differences produced between leaflet thicknesses of 0.20, 0.25 and 0.30 mm and for bioprosthetic and polymeric leaflet material models.

Results

In all cases, peak stresses occurred close to the modelled suture lines joining the leaflets and the skirt and high stresses were also present along axially aligned folds in the leaflets. Stresses were lower for the polymeric leaflets.

Conclusion

Successful simulation of crimping requires a finely resolved skirt mesh. Leaflet stresses during crimping are dependent on leaflet thickness, material properties and the ratio of leaflet volume to the available volume inside the crimped valve.
Influence of Fe+2 on the biomass, pigments, and essential fatty acids of ‏Arthrospira platensis
Authors: El-Sheekh Mostafa M. , Salman Jasim M. , Grmasha Ruqayah Ali , Abdul-Adel Esraa , Saleh Mayson Mahdi , Al-sareji Osamah J.
Published: March 2022

The effects of different ferrous sulfate (FeSO4) concentrations on the fatty acid profile of the blue-green alga Arthrospira platensis cultured in Zarrouk’s medium to produce biodiesel were studied. Different ferrous sulfate concentrations (0, 0.005, 0.01, 0.05, and 0.1 g/L) and 0.01 g/L were examined on the biochemical composition of the alga and fatty acids profile of A. platensis. Findings revealed that the highest and lowest yields of fatty acid were 0 and 0.1 g/L FeSO4, respectively. It was also noticed an increase of palmitic acid, oleic acid, linoleic acid, γ-linolenic acid, and docosahexaenoic acid when ferrous sulfate was between 0.05 and 0.1 g/L, while these fatty acids decreased at low concentration. Ferrous sulfate at a concentration of 0.1 g/L exhibited an increase and best yields in the following: growth rate and the shortest doubling time, chlorophyll-a, phycocyanin, allophycocyanin, phycobiliproteins, and carotenoids. Thus, increasing the FeSO4 concentration to 0.1 g/L has led to the increase in fatty acid individuals, which in turn, resulted in potential enhancement of the biodiesel production from A. platensis.
Do Bioresorbable Vascular Scaffold Stents Reduce Very Late Stent Thrombosis? A Systematic Review
Authors: Sharifkazemi Mohammadbagher , Zafar Haroon , Sharif Ruth , Wyns William , Sharif Faisal
Published: March 2022

Given the complications caused by stents, especially acute thrombosis, and the late and very late stent thrombosis (VLST) following percutaneous intervention (PCI) in patients, bioresorbable vascular scaffolds (BRSs) have been designed in recent years, so that their absorbance over 3 years can help eliminate the complications of non-absorbable scaffolds in the coronary arteries. Nevertheless, some studies have demonstrated their ineffectiveness or even the increased incidence of short-term and late thrombosis compared to drug-eluting stents (DESs). Studies including cohorts and registry studies as well as clinical trials have been conducted to compare these two types of stents in terms of the incidence of VLST over a period of more than 1 year. The present systematic review study investigates randomized clinical trials conducted over the last 10 years to compare the incidence rates of VLST as a result of BRSs versus DESs. A total of 11 articles were found that had investigated VLST in randomized clinical trials, and the results of two of the articles showed an increase in these complications with BRS. Therefore, until further studies are conducted and more acceptable results are obtained, we recommend that these types of stents only be used in cases where they are required according to the standards.
Development of Obstetric Practice During the Early Islamic Era
Authors: Fadel Hossam E. , Al-Hendy Ayman
Published: March 2022

Art of healing was considered the most noble of human undertakings by Islamic scholars. Acquiring medical manuscripts from previous civilizations and translating them into Arabic proceeded at a great pace. This was followed by the emergence of several great physician scientists who examined these writings, corrected many, and proceeded to produce their own, with the addition of significant original paradigm-shifting contributions to all branches of science and medicine. This article highlights some of the most important contributions to obstetrics of several prominent scholars of the early Islamic period (700–1300 A.D.)
Did Myzus persicae (Sulzer) from potato reared on a novel host for 15 years retain its host-related properties?
Authors: Clark Catherine , Boquel Sébastien , Pelletier Yvan , Goyer Claudia
Published: March 2022

Myzus persicae (Sulzer) is an important agricultural pest worldwide causing major economic losses due to its ability to transmit over 100 viruses including Potato virus Y (PVY). Myzus persicae shows considerable variation with respect to performance on its host plants. The objective of this study was to use a survival experiment, behavioural observations, including observations of probing and feeding behaviour obtained using the electrical penetration graph (EPG) technique, and a PVY acquisition experiment to determine whether or not potato was still the more suitable host for M. persicae originating on potato and reared on a novel host, table beet, for over 15 years. In a survival experiment, the pre-reproductive period was significantly longer while adult survival and whole longevity were significantly lower for M. persicae reared on beet fed beet leaves compared to M. persicae reared on potato fed potato leaves. The number of progenies produced and fecundity were both significantly reduced (90 and 85%, respectively) for M. persicae reared on beet fed beet leaves. Ethological observations and EPG assessment of M. persicae behaviour reared on beet placed on beet leaves showed significantly impaired behavioural responses compared to M. persicae reared on potato placed on potato leaves. The rate of PVY acquisition was the same for M. persicae reared on beet and on potato. These results indicate that after 15 years on table beet, M. persicae still performs better on its original host, potato, and appears to be a specialized potato-adapted genotype.
Study of the electron–atom collisions in dense semiclassical plasma of noble gases
Authors: Dzhumagulova Karlygash N. , Shalenov Erik O. , Tashkenbayev Yerkhan A. , Ramazanov Tlekkabyl S.
Published: March 2022

We present the effective optical potential of the interaction of an electron with an atom in dense semiclassical plasma of noble gases. This potential takes into account the collective screening effect and the quantum mechanical effect of diffraction. The influence of diffraction and screening effects on the characteristics of electron–atom collisions was investigated. Scattering phase shifts decrease with increase of the de Broglie wave. The electron–atom momentum-transfer cross-section at

$\lambda _{B}\to 0$

tends to the data obtained earlier with a neglecting of the diffraction effect.
Spinoza on the Distinction Between Substance and Attribute
Authors: Salgado Borge Antonio
Published: March 2022

I examine Spinoza's claim in the Metaphysical Thoughts (CM) that the attributes of God are only distinguished by a distinction of reason. I contend that for Spinoza essential attributes, such as Thought or Extension, cannot be distinguished by Francisco Suarez's distinction of reasoning reason, as Martin Lin (2019) suggests, nor can he be using Suárez’ distinction of reasoned reason for this purpose, as Yitzhak Melamed (2017) believes. Since reasoning reason and the distinction of reasoned reason are the only two kinds of rational distinction available to Spinoza, it follows that for him the distinction between God's essential attributes in the CM cannot be a distinction of reason. But I show that Spinoza is not mistakenly using Suarez's distinction in the CM. Rather, I argue, Spinoza consistently follows Suárez and uses reasoned reason to distinguish between God's necessary properties and not between God's essential attributes.
Podcasting past the paywall: How diverse media allows more equitable participation in linguistic science
Authors: Figueroa Megan
Published: March 2022

The paywall blocks broad participation in scientific discourse, and it is both financial and psychological. The financial paywall makes access to peer-reviewed research prohibitively expensive for many researchers. The psychological paywall refers to the gatekeeping nature of academic language. Elites hoard the products of scientific research and gatekeep membership in the specialist communities via arcane vocabulary and discourse structures, together with imposition of a tone that demands dispassionate engagement with topics that are urgent and painful to the participants of their research. To exclude the perspectives of those outside the ivory tower is to dismiss unique experiences and epistemologies, essentially blocking diversity of thought in linguistic science. A range of tools is needed to undermine this power structure. Here I highlight one, which is diverse media, in general, and podcasting, specifically. Podcasting brings diverse views into the conversation and allows racially offensive ideas to be understood as such so they can then be challenged. I present the case study of the putative so-called “30-million-word gap”—the claim that, by the time they are four years old, historically marginalized children are exposed to thirty million fewer words than middle- and upper-class white children. I use this notion, which is preposterous on its face, to illustrate the emancipatory potential of the podcast medium.
Totally anomalous “double drainage” of pulmonary venous confluence: case report with embryological aspects
Authors: Rajagopal Rengarajan , Sharma Smily , Agarwal Ritu
Published: March 2022

Double drainage of the confluence of all four pulmonary veins is extremely rare. We present the image findings in a child with double drainage of the pulmonary venous confluence into the coronary sinus and left superior caval vein with co-existent right superior caval venous stenosis.
Antiblack Joy
Authors: Vaziri Parisa
Published: March 2022

Maryam Khakipour’s 2004 The Joymakers and its 2008 sequel Shadi form an exemplary site for examining the dissemination and translation of Persian blackface across time, space, and media. The transmediality of sīyāh bāzī reveals a universal familiarity with the practice of blackface comedy that disrupts commonplace assumptions about its geographical and historical itinerary.
Kaddish
Authors: Kolankiewicz Leszek , Rusek Mirosław
Published: March 2022

Ludwik Flaszen was the cofounder and literary adviser of the Polish Laboratory Theatre, and a collaborator of Jerzy Grotowski. This Jewish kaddish and Dionysian dithyramb offers a glimpse of his life and work.
Unconstitutional constitutional amendment or constitutional dismemberment? A reappraisal of the presidential term limit amendment in Cameroon
Authors: Enonchong Laura-Stella
Published: March 2022

Presidential term limit provisions are often perceived as a feature of modern democratic systems. It has been argued that their existence is a key intervention mechanism to pre-empt some undemocratic outcomes associated with incumbency advantages. In 2008, the Constitution of Cameroon was amended to abolish the presidential term limit. More than ten years on, there are ostensible signs of a democratic decline. This article takes a retrospective look at the constitutional amendment to assess its constitutionality. It is argued that a conclusion on the constitutionality of the amendment may not be unequivocal. Nevertheless, there are substantial grounds for considering the constitutional change as a constitutional dismemberment. This is premised on the fact that, although the amendment followed the normal rules for constitutional amendments, the transformation amounted to a fundamental break with the constitutional commitment to democracy that underpinned the adoption of the 1996 Constitution.
Do We Judge Fiction by the Author’s Gender?
Authors: Ivanski Chantelle , Humphries Stacey , van Dalen-Oskam Karina , Mar Raymond A.
Published: March 2022

Abstract. Female authors of fiction often perceive themselves to be undervalued in relation to their male counterparts. What is not clear is whether this preference for male authors comes from readers or publishers. Two pre-registered studies examined how university students evaluated book passages attributed to either male or female authors, and investigated whether negative evaluations of romance novels are based on their association with women. In Study 1, participants read identical passages attributed to either male or female authors and evaluated them. Study 2 extended this work by adding attributions of genre: either romance or literary fiction. Linear mixed-effects modeling and Bayesian analyses were employed to analyze these data. Study 1 demonstrated little preference for books attributed to males over females and Bayesian analyses confirmed support for the null in most cases. The results of Study 2 similarly suggested that author gender and genre attributions do not have a strong influence on evaluations.
Line‐Source Model Based Rapid Inversion for Deriving Large Earthquake Rupture Characteristics Using High‐Rate GNSS Observations
Authors: Zheng Jiawei , Fang Rongxin , Li Min , Lv Huanghui , Liu Jingnan
Published: March 2022

We present a new method using Global Navigation Satellite System‐derived peak ground velocities to rapidly determine rupture characteristics for large earthquakes (Mw > 6). A three‐step strategy is adopted to sequentially estimate the fault rupture length, direction, and pattern (unilateral or bilateral). It does not require any a priori constraint on the fault plane, and can avoid drift and clipping problems in seismic data based inversion methods. Through retrospective analysis of six recent large earthquakes, the line‐source rupture characteristics can be determined within 30 s. Comparison with the United States Geological Survey released products demonstrates that the line‐source parameters can be estimated with considerable accuracy. We also analyze the contribution of the earthquake rupture characteristics to the prediction of ground shaking intensity. It is shown that the method has the potential to improve ground shaking predictions with applications in disaster assessment and emergency response.
H2O2and CH3OOH (MHP) in the Remote Atmosphere: 2. Physical and Chemical Controls
Authors: Allen Hannah M. , Bates Kelvin H. , Crounse John D. , Kim Michelle J. , Teng Alexander P. , Ray Eric A. , Wennberg Paul O.
Published: March 2022

Hydrogen peroxide (H2O2) and methyl hydroperoxide (MHP, CH3OOH) serve as HOx(OH and HO2radicals) reservoirs and therefore as useful tracers of HOxchemistry. Both hydroperoxides were measured during the 2016–2018 Atmospheric Tomography Mission as part of a global survey of the remote troposphere over the Pacific and Atlantic Ocean basins conducted using the NASA DC‐8 aircraft. To assess the relative contributions of chemical and physical processes to the global hydroperoxide budget and their impact on atmospheric oxidation potential, we compare the observations with two models, a diurnal steady‐state photochemical box model and the global chemical transport model Goddard Earth Observing System (GEOS)‐Chem. We find that the models systematically under‐predict H2O2by 5%–20% and over‐predict MHP by 40%–50% relative to measurements. In the marine boundary layer, over‐predictions of H2O2in a photochemical box model are used to estimate H2O2boundary‐layer mean deposition velocities of 1.0–1.32 cm s−1, depending on season; this process contributes to up to 5%–10% of HOxloss in this region. In the upper troposphere and lower stratosphere, MHP is under‐predicted and H2O2is over‐predicted by a factor of 2–3 on average. The differences between the observations and predictions are associated with recent convection: MHP is under‐estimated and H2O2is over‐estimated in air parcels that have experienced recent convective influence.
Chemically Induced Evolution of Morphological and Connectivity Characteristics of Pore Space of Complex Carbonate Rock via Digital Core Analysis
Authors: Qajar Jafar , Arns Christoph H.
Published: March 2022

We study the impact of reactive flow on a complex carbonate rock whose pore space was resolved by X‐ray μ‐CT. A small core plug was imaged in the original and chemically altered states. The morphology of the resolved pore space was quantified using various approaches, such as sample‐spanning cluster analysis, capillary drainage transform (CDT), and Minkowski functionals. In particular, we carefully evaluated the changes in macropore connectivity by calculating the fraction of percolated cluster, the Euler characteristic of macroporous phase, and the critical pore diameter in pre‐ and post‐alteration states. We observed that the reactive flow mainly affected larger pores in the macropore region of the sample. More importantly, a huge increase in macropore connectivity, as indicated majorly by the CDT measurements and the Euler characteristic, was observed such that the poorly connected original macropore phase was converted to well‐connected ones after the reactive flow. In addition, the increases in the macropore surface area and integral mean curvature indicated that the oomoldic and interooidal pores of the rock were dominantly enlarged by the reactive fluid. Based on direct numerical simulations on the main flow paths (i.e., the macro‐connected pore phase), strong correlations were found between changes in transport properties and the evolution of connectivity and length scales of the macropore phase, such that simple power‐law models could be used to predict with acceptable accuracy. This suggests that the evolution of transport properties of the rock was mainly controlled by the changes in the macro‐connected porosity and the critical pore diameter.
Exposures to FD&C synthetic color additives from over-the-counter medications and vitamins in United States children and pregnant women
Authors: Thilakaratne Ruwan , Castorina Rosemary , Gillan Mayela , Han Dorothy , Pattabhiraman Teja , Nirula Anuroop , Miller Mark D. , Marty Melanie , Lehmkuhler Arlie , Mitchell Alyson , Bradman Asa
Published: March 2022

Background

Food and Drug Administration (FDA) Food Drug and Cosmetic (FD&C) synthetic color additives (SCAs) have been associated with attentional and behavioral problems in children. Efforts to quantify exposure have focused on foods, while the contribution of medications and supplements remains unknown.

Objective

To estimate exposures to SCAs in children (2–16 years) and pregnant women from intake of common over-the-counter (OTC) medications and vitamins.

Methods

We estimated single-day exposure (mg/kg/day) to FD&C SCAs based on measurements of 25 different products and recommended dosages on product labels. Exposures were compared to SCA exposure estimates from food we previously developed and acceptable daily intakes (ADIs) established by FDA and the World Health Organization.

Results

The highest exposure was found for FD&C Red No. 40 in a children’s cold/cough/allergy syrup. A child aged 12–16 years consuming the maximum daily dosage would have an exposure of 0.221 mg/kg/day, which is twice this age group’s typical exposure to this additive from food. No estimated exposures exceeded the ADIs.

Significance

Some children’s OTC medications and vitamins may cause daily SCA exposures comparable to those from foods. OTC medications and vitamins should be considered in efforts to quantify population exposure to FD&C SCAs.

Impact

Exposure to synthetic color additives (SCAs) from foods has been associated with behavioral problems in children. Exposures from over-the-counter (OTC) medications and vitamins remain unquantified despite widespread use. We estimated exposures in children and pregnant women for 25 different OTC medication and vitamin products sold in the United States. While exposures were below acceptable daily intakes (ADIs) established by the US Food and Drug Administration and the World Health Organization, some were comparable to typical daily exposures from foods. This work critically informs future SCA exposure assessments and provides valuable information for parents concerned about the health effects of SCAs.
miR-32 promotes MYC-driven prostate cancer
Authors: Scaravilli Mauro , Koivukoski Sonja , Gillen Andrew , Bouazza Aya , Ruusuvuori Pekka , Visakorpi Tapio , Latonen Leena
Published: March 2022

miR-32 is an androgen receptor (AR)-regulated microRNA, expression of which is increased in castration-resistant prostate cancer (PC). We have previously shown that overexpression of miR-32 in the prostate of transgenic mice potentiates proliferation in prostate epithelium. Here, we set out to determine whether increased expression of miR-32 influences growth or phenotype in prostate adenocarcinoma in vivo. We studied transgenic mice expressing MYC oncogene (hiMYC mice) to induce tumorigenesis in the mouse prostate and discovered that transgenic overexpression of miR-32 resulted in increased tumor burden as well as a more aggressive tumor phenotype in this model. Elevated expression of miR-32 increased proliferation as assessed by Ki-67 immunohistochemistry, increased nuclear density, and higher mitotic index in the tumors. By gene expression analysis of the tumorous prostate tissue, we confirmed earlier findings that miR-32 expression regulates prostate secretome by modulating expression levels of several PC-related target genes such asSpink1,Spink5, andMsmb. Further, we identifiedPdk4as a tumor-associated miR-32 target in the mouse prostate. Expression analysis ofPDK4in human PC reveals an inverse correlation with miR-32 expression and Gleason score, a decrease in castration-resistant and metastatic tumors compared to untreated primary PC, and an association of lowPDK4expression with a shorter recurrence-free survival of patients. Although decreased PDK4 expression induces the higher metabolic activity of PC cells, induced expression of PDK4 reduces both mitotic respiration and glycolysis rates as well as inhibits cell growth. In conclusion, we show that miR-32 promotes MYC-induced prostate adenocarcinoma and identifies PDK4 as a PC-relevant metabolic target of miR-32-3p.
Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm
Authors: Jia Yiting , Zhang Lu , Liu Ziyi , Mao Chenfeng , Ma Zihan , Li Wenqiang , Yu Fang , Wang Yingbao , Huang Yaqian , Zhang Weizhen , Zheng Jingang , Wang Xian , Xu Qingbo , Zhang Jian , Feng Wei , Yun Caihong , Liu Chuanju , Sun Jinpeng , Fu Yi , Cui Qinghua , Kong Wei
Published: March 2022

Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there is no proven drug treatment for this condition. In this study, by using the Connectivity Map (CMap) approach, we explored naringenin, a naturally occurring citrus flavonoid, as a putative agent for inhibiting AAA. We then validated the prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice and angiotensin II-infused ApoE−/− mice. Naringenin effectively blocked the formation of AAAs and the progression of established AAAs. Transcription factor EB (TFEB) is the master regulator of lysosome biogenesis. Intriguingly, the protective role of naringenin on AAA was abolished by macrophage-specific TFEB depletion in mice. Unbiased interactomics, combined with isothermal titration calorimetry (ITC) and cellular thermal shift assays (CETSAs), further revealed that naringenin is directly bound to 14-3-3 epsilon blocked the TFEB-14-3-3 epsilon interaction, and therefore promoted TFEB nuclear translocation and activation. On one hand, naringenin activated lysosome-dependent inhibition of the NLRP3 inflammasome and repressed aneurysmal inflammation. On the other hand, naringenin induced TFEB-dependent transcriptional activation of GATA3, IRF4, and STAT6 and therefore promoted reparative M2 macrophage polarization. In summary, naturally derived naringenin or macrophage TFEB activation shows promising efficacy for the treatment of AAA.
Possibility for strong northern hemisphere high-latitude cooling under negative emissions
Authors: Schwinger Jörg , Asaadi Ali , Goris Nadine , Lee Hanna
Published: March 2022

It is well established that a collapse or strong reduction of the Atlantic meridional overturning circulation (AMOC) would substantially cool the northern high latitudes. Here we show that there is a possibility that such cooling could be amplified under deliberate CO2 removal and result in a temporary undershoot of a targeted temperature level. We find this behaviour in Earth system models that show a strong AMOC decline in response to anthropogenic forcing. Idealized simulations of CO2 removal with one of these models indicate that the timing of negative emissions relative to AMOC decline and recovery is key in setting the strength of the temporary cooling. We show that the pronounced temperature-fluctuations at high northern latitudes found in these simulations would entail considerable consequences for sea-ice and permafrost extent as well as for high latitude ecosystems.
Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
Authors: Yoo Jung-Yoon , Kim Tae Hoon , Shin Jung-Ho , Marquardt Ryan M. , Müller Ulrich , Fazleabas Asgerally T. , Young Steven L. , Lessey Bruce A. , Yoon Ho-Geun , Jeong Jae-Wook
Published: March 2022

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6d/d mice revert to their normal expression in Mig-6d/dErbb2d/d mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.
Exchange-biased topological transverse thermoelectric effects in a Kagome ferrimagnet
Authors: Zhang Heda , Koo Jahyun , Xu Chunqiang , Sretenovic Milos , Yan Binghai , Ke Xianglin
Published: March 2022

Kagome metal TbMn6Sn6 was recently discovered to be a ferrimagnetic topological Dirac material by scanning tunneling microscopy/spectroscopy measurements. Here, we report the observation of large anomalous Nernst effect and anomalous thermal Hall effect in this compound. The anomalous transverse transport is consistent with the Berry curvature contribution from the massive Dirac gaps in the 3D momentum space as demonstrated by our first-principles calculations. Furthermore, the transverse thermoelectric transport exhibits asymmetry with respect to the applied magnetic field, i.e., an exchange-bias behavior. Together, these features place TbMn6Sn6 as a promising system for the outstanding thermoelectric performance based on anomalous Nernst effect.
Different expression of circulating microRNA profile and plasma SP-D in Tibetan COPD patients
Authors: Shi Xue-feng , He Xiang , Sun Ze-rui , Wang Jian-xiang , Gu Yu-hai , Xie You-bang , Duo Jie
Published: March 2022

COPD is the fourth leading cause of mortality, and is predicted to be the third leading cause of death worldwide by 2020. But few studies on Tibetan COPD of China. This study identifies distinctive miRNA signatures in Tibetan COPD patients from Tibetan healthy subjects that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. In this study, a total of 210 differentially expressed miRNAs were screened. Analysis of the functions of target genes of differentially expressed miRNAs via GO enrichment analysis revealed that they mainly influenced guanyl-nucleotide exchange factor activity, cell morphogenesis and the positive regulation of GTPase activity. KEGG pathway enrichment analysis showed that these target genes were mainly enriched in signaling by NGF, Axon guidance, developmental biology, ubiquitin mediated proteolysis, and PDGF signaling pathways. MiR-106-5p and miR-486-5p expression was validated in the complete cohort. Age, plasma miR-106-5p, miR-486-5p, SP-D protein levels, and SP-D mRNA level were also determined to be correlated with FEV1%Pred, and may as the risk factors of Tibetan COPD. The combination of plasma miR-106-5p, miR-486-5p and SP-D mRNA expression may be the best model to assist the diagnosis of Tibetan COPD.
Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation
Authors: Gallego-Durán Rocío , Ampuero Javier , Pastor-Ramírez Helena , Álvarez-Amor Leticia , del Campo Jose Antonio , Maya-Miles Douglas , Montero-Vallejo Rocío , Cárdenas-García Antonio , Pareja Mª Jesús , Gato-Zambrano Sheila , Millán Raquel , del Carmen Rico María , Luque-Sierra Amparo , Gil-Gómez Antonio , Rojas Ángela , Muñoz-Hernández Rocío , García-Lozano María , Aller Rocío , Andrade Raúl J. , García-Monzón Carmelo , Andreola Fausto , Martín Francisco , Jalan Rajiv , Romero-Gómez Manuel
Published: March 2022

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr −/−). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m2), diabetes mellitus and ALT were
found to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.
Quantum teleportation with one classical bit
Authors: Parakh Abhishek
Published: March 2022

Quantum teleportation allows one to transmit an arbitrary qubit from point A to point B using a pair of (pre-shared) entangled qubits and classical bits of information. The conventional protocol for teleportation uses two bits of classical information and assumes that the sender has access to only one copy of the arbitrary qubit to be sent. Here, we ask whether we can do better than two bits of classical information if the sender has access to multiple copies of the qubit to be teleported. We place no restrictions on the qubit states. Consequently, we propose a modified quantum teleportation protocol that allows Alice to reset the state of the entangled pair to its initial state using only local operations. As a result, the proposed teleportation protocol requires the transmission of only one classical bit with a probability greater than one-half. This has implications for efficient quantum communications and the security of quantum cryptographic protocols based on quantum entanglement.
Synthetic correlated diffusion imaging hyperintensity delineates clinically significant prostate cancer
Authors: Wong Alexander , Gunraj Hayden , Sivan Vignesh , Haider Masoom A.
Published: March 2022

Prostate cancer (PCa) is the second most common cancer in men worldwide and the most frequently diagnosed cancer among men in more developed countries. The prognosis of PCa is excellent if detected at an early stage, making early screening crucial for detection and treatment. In recent years, a new form of diffusion magnetic resonance imaging called correlated diffusion imaging (CDI) was introduced, and preliminary results show promise as a screening tool for PCa. In the largest study of its kind, we investigate the relationship between PCa presence and a new variant of CDI we term synthetic correlated diffusion imaging (CDI$$^s$$

s

), as well as its performance for PCa delineation compared to current standard MRI techniques [T2-weighted (T2w) imaging, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging] across a cohort of 200 patient cases. Statistical analyses reveal that hyperintensity in CDI$$^s$$

s

is a strong indicator of PCa presence and achieves strong delineation of clinically significant cancerous tissue compared to T2w, DWI, and DCE. These results suggest that CDI$$^s$$

s

hyperintensity may be a powerful biomarker for the presence of PCa, and may have a clinical impact as a diagnostic aid for improving PCa screening.
A sensitivity study of rising compound coastal inundation over large flood plains in a changing climate
Authors: Peter Sheng Y. , Paramygin Vladimir A. , Yang Kun , Rivera-Nieves Adail A.
Published: March 2022

Coastal flood hazards and damage to coastal communities are increasing steeply and nonlinearly due to the compound impact of intensifying tropical cyclones (TCs) and accelerating sea-level rise (SLR). We expand the probabilistic coastal flood hazard analysis framework to facilitate coastal adaptation by simulating the compound impact of predicted intensifying TCs and rising sea levels in the twenty-first century. We compared the characteristics of landfalling TCs in Florida (FL) and southwest Florida (SWFL) for the late twentieth and twenty-first centuries predicted by several climate models and downscaling models. TCs predicted by four climate models, one without downscaling and three with downscaling, were used by a coupled surge-wave model to predict the future flood hazard due to compound effects of TCs and SLR over a large SWFL coastal flood plain. By 2100, the coastal inundation metrics of the 1% annual chance coastal flood could become almost 3–7 folds of their current values, depending on the climate and downscaling models, Representative Concentration Pathway scenarios, Atlantic Multi-decadal Oscillation phases, TCs, SLR, precipitation, and how TCs and SLR are incorporated. By 2100, the current 1% (100-year) inundation event could become a 3-year event, and the 0.2% (500-year) inundation event could become a 5-year event.
SARS-CoV-2 enzyme-linked immunosorbent assays as proxies for plaque reduction neutralisation tests
Authors: Kay Grant A. , Owen Sophie I. , Giorgi Emanuele , Clark David J. , Williams Christopher T. , Menzies Stefanie , Cuevas Luis E. , Davies Benedict M. O. , Eckersley Nicholas M. , Hughes Grant L. , Kirwan Daniela E. , Krishna Sanjeev , Patterson Edward I. , Planche Tim , Staines Henry M. , Adams Emily R.
Published: March 2022

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8–99.9] sensitive and 88.9% [95% CI 51.8–99.7] specific at predicting the presence of NAbs (PRNT80 > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.
Magnetisation switching dynamics induced by combination of spin transfer torque and spin orbit torque
Authors: Meo Andrea , Chureemart Jessada , Chantrell Roy W. , Chureemart Phanwadee
Published: March 2022

We present a theoretical investigation of the magnetisation reversal process in CoFeB-based magnetic tunnel junctions (MTJs). We perform atomistic spin simulations of magnetisation dynamics induced by combination of spin orbit torque (SOT) and spin transfer torque (STT). Within the model the effect of SOT is introduced as a Slonczewski formalism, whereas the effect of STT is included via a spin accumulation model. We investigate a system of CoFeB/MgO/CoFeB coupled with a heavy metal layer where the charge current is injected into the plane of the heavy metal meanwhile the other charge current flows perpendicular into the MTJ structure. Our results reveal that SOT can assist the precessional switching induced by spin polarised current within a certain range of injected current densities yielding an efficient and fast reversal on the sub-nanosecond timescale. The combination of STT and SOT gives a promising pathway to improve high performance CoFeB-based devices with high speed and low power consumption.