bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of COVID‐19 infection in pediatric pulmonary hypertension: A single‐center experience
Authors: Morales‐Demori Raysa , Mallory George B. , Chartan Corey , Coleman Ryan , Ruiz Fadel , Villafranco Natalie , Whalen Elise , Varghese Nidhy
Published: August 2021

Background

The global COVID‐19 pandemic was particularly concerning for the pediatric pulmonary hypertension (PH) population due to immature immune systems and developmental comorbidities. This study aims to describe a single‐center experience of pediatric PH patients diagnosed with COVID‐19 disease.

Methods

A retrospective cohort study of all pediatric patients followed by the PH Center at Texas Children's Hospital diagnosed with COVID‐19 infection from April 2020 to February 2021.

Results

We identified 23 patients with a median age of 58 months (interquartile range [IQR]: 25–75th, 21–132 months), 48% being Hispanics. Eight patients (35%) required hospitalization; median length of stay was 6 days (IQR: 25–75th, 5–8 days). Only three of these eight patients required increased respiratory support. Targeted PH therapy was escalated in four patients (two in dual and two in triple therapy). There was one mortality in a patient with failing Fontan physiology. Ninety‐one percent of patients have had post‐COVID outpatient follow‐up, median of 101 days (IQR: 25–75th, 50–159 days) from diagnosis. Of the five patients with 6 min walk test (6MWT) data, three (60%) children walked less distance, median of −12 m (IQR: 25–75th, −12 to +49 m) compared to pre‐COVID testing. Postinfection pulmonary function testing (PFT) was notable for decrease in predicted forced vital capacity (FVC; median −6%, range −11% to +6%) and forced expiratory volume in one second (FEV1; median −14%, range −12% to −18%) in 75% of the patients with PFT data.

Conclusion

In our institution, COVID‐19 was found more frequently in Hispanics and associated with low mortality.
A new approach for analysis of polyprenols by a combination of thin‐film chemical deposition and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Gladchuk Alexey S. , Krasnov Konstantin A. , Keltsieva Olga A. , Kalninia Yana K. , Alexandrova Marina L. , Ivanov Nikita S. , Muradymov Marat Z. , Krasnov Nikolai V. , Reynyuk Vladimir L. , Sukhodolov Nikolai G. , Podolskaya Ekaterina P.
Published: August 2021

Rationale

The polyprenols are involved in some essential biosynthetic pathways and serve as ubiquitous components of cellular membranes, so their fingerprinting in natural samples is of great interest. Previous studies indicate that due to the high hydrophobicity of polyprenols their direct analysis by mass spectrometry with soft ionization techniques may be difficult and require preliminary off‐line derivatization. Hence, a method for rapid and sensitive screening of polyprenols is required.

Methods

A combination of thin‐film chemical deposition and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) was used for analysis of the polyprenol profile of Abies sibirica L. extract. Polyprenol‐based monolayers were formed at the interphase of aqueous barium acetate solution, supplemented with 2,5‐dihydroxybenzoic acid, and an n‐hexane solution of polyprenols directly on a MALDI target plate.

Results

Peaks corresponding to [M − H + Ba]+ ions were observed in the MALDI‐TOF mass spectra of polyprenols. A total of nine polyprenol homologues were identified with a polyprenol of 16 isoprene units dominating. The limit of detection was established at the level of 6 pg. Possible mechanisms of formation of [M − H + Ba]+ ions of polyprenols were discussed.

Conclusions

The proposed approach can be suitable for high‐throughput screening of polyprenols in biological samples of different origin due to easy sample preparation and high sensitivity.
Leveraging curricular and students' resources to instigate and sustain problematizing
Authors: Ko Mon‐Lin Monica
Published: August 2021

Although existing literature suggests that teachers perceive, mobilize, and leverage resources to support ambitious instruction, less is known about how teachers and students jointly take up resources for co‐constructing scientific knowledge. This study examines how teachers and students utilize aspects of practice‐oriented curriculum materials and students' everyday experiences as resources to problematize aspects of their scientific inquiry. I present an analysis of how teachers and students employ resources to engage in problematizing as they enact the same lessons from a practice‐oriented science curriculum in sixth grade science classrooms. I report on patterns of variability in who leverages what resources to instigate and sustain problematizing, and whether or not the problematizing is in service of or deviates from the curricular intent. I present three representative cases to highlight the tensions that emerge between students' everyday experiences and carefully sequenced curriculum materials. The findings reported here have implications for the design of practice‐oriented curriculum materials, teachers professional learning around curriculum use, and the opportunities for redistribution of students' epistemic agency during curriculum enactment.
Oxygen electrochemistry in Li‐O2 batteries probed by in situ surface‐enhanced Raman spectroscopy
Authors: Wang Jiawei , Ma Lipo , Xu Junyuan , Xu Ye , Sun Ke , Peng Zhangquan
Published: August 2021

Surface‐enhanced Raman spectroscopy (SERS), as a nondestructive and ultra‐sensitive single molecular level characterization technique, is a powerful tool to deeply understand the interfacial electrochemistry reaction mechanism involved in energy conversion and storage, especially for oxygen electrochemistry in Li‐O2 batteries with unrivaled theoretical energy density. SERS can provide precise spectroscopic identification of the reactants, intermediates and products at the electrode|electrolyte interfaces, independent of their physical states (solid and/or liquid) and crystallinity level. Furthermore, SERS's power to resolve different isotopes can be exploited to identify the mass transport limitation and reactive sites of the passivated interface. In this review, the application of in situ SERS in studying the oxygen electrochemistry, specifically in aprotic Li‐O2 batteries, is summarized. The ideas and concepts covered in this review are also extended to the perspectives of the spectroelectrochemistry in general aprotic metal‐gas batteries.
Oxymatrine hydrazone (OMTH) synthesis and its protective effect for rheumatoid arthritis through downregulation of MEK/NF‐κB pathway
Authors: Zhang Guangwen , Liu Baojian , Zeng Zhaoyang , Chen Qinghai , Feng Yiyun , Ning Xueqian
Published: August 2021

Rheumatoid arthritis (RA) is one of the inflammatory diseases detected in more than 1% of the world population. In the present study, oxymatrine hydrazone (OMTH) was synthesized and investigated for treatment of RA in vitro in TNF‐α induced fibroblast‐like synoviocyte cell model. Cell viability and apoptosis were detected using MTT and flow cytometry assays, respectively. ELISA was used for determination of inflammatory cytokines and western blotting for evaluation of protein expression. Pretreatment of HFLS‐RA cells with 0.5, 1.0, 1.5, 2.0, and 2.5 μM doses of OMTH suppressed TNF‐α induced promotion of proliferative potential in dose‐based manner. The OMTH pretreatment of TNF‐α exposed HFLS‐RA cells significantly increased apoptotic cell proportion. In TNF‐α exposed HFLS‐RA cells OMTH pretreatment elevated Bax and suppressed Bcl‐2 expression. Treatment of HFLS‐RA cells with OMTH prevented TNF‐α mediated elevation of IL‐1β, IL‐6 and IL‐8. Moreover, OMTH treatment of HFLS‐RA cells effectively suppressed TNF‐α mediated elevated levels of MMP‐1 and MMP‐13. Pretreatment of HFLS‐RA cells with OMTH reversed TNF‐α mediated promotion of iNOS and COX‐2 levels. The MEK/1/2 and p65 phosphorylation in TNF‐α exposed HFLS‐RA cells was reduced by OMTH pre‐treatment in dose‐based manner. Thus, OMTH successfully inhibited TNF‐α‐mediated increased viability of RA synovial cells and activated apoptosis. Pretreatment of TNF‐α exposed synovial cells with OMTH targeted phosphorylation of MEK/NF‐κB. Therefore, OMTH may act as potential therapeutic agent for RA treatment.
It takes two (or more): The social nature of secrets
Authors: Bedrov Alisa , Gable Shelly , Liberman Zoe
Published: August 2021

The lion's share of research on secrecy focuses on how deciding to keep or share a secret impacts a secret‐keeper's well‐being. However, secrets always involve more than one person: the secret‐keeper and those from whom the secret is kept or shared with. Although secrets are inherently social, their consequences for people's reputations and social relationships have been relatively ignored. Secrets serve a variety of social functions, including (1) changing or maintaining one's reputation, (2) conveying social utility, and (3) establishing friendship. For example, if Beth has a secret about a past misdemeanor, she might not tell any of her friends in order to maintain her reputation as an outstanding citizen. If Beth does share this secret with her friend Amy, Amy could interpret this as a sign of trust and think that their friendship is special. However, Amy could also choose to share Beth's secret with the rest of the friend group to show that she is a useful member with access to valuable information about others. Attention to these social functions of secrets emerges from a young age, and secrets play a prominent role in human relationships throughout the lifespan. After providing an overview of what is currently known about the relational consequences of secrecy in childhood and adulthood, we discuss how social and developmental psychologists could work together to broaden our understanding of the sociality of secrets. Future steps include incorporating more dyadic and social network analyses into research on secrets and looking at similar questions across ages.

This article is categorized under:

Psychology > Reasoning and Decision Making
Thermal stress analysis in a hemispherical shell made of transversely isotropic materials under pressure and thermo‐mechanical loads
Authors: Thakur Pankaj , Sethi Monika , Gupta Kanav , Bhardwaj Ram Krishan
Published: August 2021

This article deals with the study of thermal stress in a hemispherical shell made of transversely isotropic material under the effect of thermal, pressure and mechanical load. Seth's transition theory and generalized strain measure are used for finding the governing equation. Mathematical modelling is based on stress–strain relation and equilibrium equation. Analytical solutions are presented for the hemispherical shell made of transversely isotropic material and isotropic material. The effects of different pertinent parameters (i.e., temperature, pressure and load) are considered for the spherical shell made of transversely isotropic material. The behaviour of stress distribution, mechanical load, pressure rise, and temperature distribution are investigated. From the obtained results, it is noticed that carbon fiber material hemispherical shell requires higher pressure at the internal surface in comparison to magnesium/polypropylene material. With the introduction of mechanical load, the value of pressure decreases at the internal surface, but reverse results are obtained in the case of thermal condition for the hemispherical shell made of carbon fiber/magnesium/polypropylene material. By applying thermal condition, the hemispherical shell made of carbon fiber material requires maximum hoop stress at the external surface as compared to the magnesium/polypropylene material. The transversely isotropic material hemispherical shell more convenient than that of isotropic material hemispherical shell. Results have been discussed numerically and graphically.
Robots as My Future Colleagues: Changing Attitudes Toward Collaborative Robots by Means of Experience-Based Workshops
Authors: Leoste Janika , Viik Tõnu , López José San Martín , Kangur Mihkel , Vunder Veiko , Mollard Yoan , Õun Tiia , Tammo Henri , Paekivi Kristian
Published: August 2021

Artificial intelligence-driven robots are increasingly being introduced in various workplaces. Research implies that people’s negative attitudes toward intelligent and collaborative robots might hinder their willingness to use them. We propose that interactive educational activities such as specialized workshops help people to overcome such negative attitudes. We designed a two-day workshop that introduced two quasi-industrial robots (Poppy Ergo Jr and ClearBot) to 16 university students. Students’ attitudes were qualitatively measured before and after the workshop. The results imply that the workshop helped students to increase their understanding of the nature of the intelligent collaborative robots. More precisely, robots became to be seen as empowering tools, rather than friends or enemies. Interestingly, there were significant gender differences, as the female participants had a greater tendency to view robots as animated objects. We concluded that specialized workshops effectively lead participants to become aware of various promising opportunities for their robotic co-workers in the possible future.
Convergence Towards the Vlasov–Poisson Equation from the N-Fermionic Schrödinger Equation
Authors: Chen Li , Lee Jinyeop , Liew Matthew
Published: August 2021

We consider the quantum dynamics of N interacting fermions in the large N limit. The particles in the system interact with each other via repulsive interaction that is regularized Coulomb potential with a polynomial cutoff with respect to N. From the quantum system, we derive the Vlasov–Poisson system by simultaneously estimating the semiclassical and mean-field residues in terms of the Husimi measure.
Complete Gradient Estimates of Quantum Markov Semigroups
Authors: Wirth Melchior , Zhang Haonan
Published: August 2021

In this article we introduce a complete gradient estimate for symmetric quantum Markov semigroups on von Neumann algebras equipped with a normal faithful tracial state, which implies semi-convexity of the entropy with respect to the recently introduced noncommutative 2-Wasserstein distance. We show that this complete gradient estimate is stable under tensor products and free products and establish its validity for a number of examples. As an application we prove a complete modified logarithmic Sobolev inequality with optimal constant for Poisson-type semigroups on free group factors.
Evolution and enrichment of CYP5035 in Polyporales: functionality of an understudied P450 family
Authors: Fessner Nico D. , Nelson David R. , Glieder Anton
Published: August 2021

Bioprospecting for innovative basidiomycete cytochrome P450 enzymes (P450s) is highly desirable due to the fungi’s enormous enzymatic repertoire and outstanding ability to degrade lignin and detoxify various xenobiotics. While fungal metagenomics is progressing rapidly, the biocatalytic potential of the majority of these annotated P450 sequences usually remains concealed, although functional profiling identified several P450 families with versatile substrate scopes towards various natural products. Functional knowledge about the CYP5035 family, for example, is largely insufficient. In this study, the families of the putative P450 sequences of the four white-rot fungiPolyporus arcularius,Polyporus brumalis,Polyporus squamosusandLentinus tigrinuswere assigned, and the CYPomes revealed an unusual enrichment of CYP5035, CYP5136 and CYP5150. By computational analysis of the phylogeny of the former two P450 families, the evolution of their enrichment could be traced back to theGanodermamacrofungus, indicating their evolutionary benefit. In order to address the knowledge gap on CYP5035 functionality, a representative subgroup of this P450 family ofP.arculariuswas expressed and screened against a test set of substrates. Thereby, the multifunctional enzyme CYP5035S7 converting several plant natural product classes was discovered. Aligning CYP5035S7 to 102,000 putative P450 sequences of 36 fungal species from Joint Genome Institute-provided genomes located hundreds of further CYP5035 family members, which subfamilies were classified if possible. Exemplified by these specific enzyme analyses, this study gives valuable hints for future bioprospecting of such xenobiotic-detoxifying P450s and for the identification of their biocatalytic potential.

Graphical abstract

Key points

•The P450 families CYP5035 and CYP5136 are unusually enriched in P.arcularius.

•Functional screening shows CYP5035 assisting in the fungal detoxification mechanism.

•Some Polyporales encompass an unusually large repertoire of detoxification P450s.
Evaluation of potential tissue heating during percutaneous drill-assisted bone sampling in an in vivo porcine study
Authors: Niehues Stefan M. , Elezkurtaj Sefer , Bresssem Keno K. , Hamm Bernd , Erxleben Christoph , Vahldiek Janis , Adams Lisa C.
Published: August 2021

Background

Minimally invasive, battery-powered drilling systems have become the preferred tool for obtaining representative samples from bone lesions. However, the heat generated during battery-powered bone drilling for bone biopsies has not yet been sufficiently investigated. Thermal necrosis can occur if the bone temperature exceeds a critical threshold for a certain period of time.

Purpose

To investigate heat production as a function of femur temperature during and after battery-powered percutaneous bone drilling in a porcine in vivo model.

Methods

We performed 16 femur drillings in 13 domestic pigs with an average age of 22 weeks and an average body temperature of 39.7 °C, using a battery-powered drilling system and an intraosseous temperature monitoring device. The standardized duration of the drilling procedure was 20 s. The bone core specimens obtained were embedded in 4% formalin, stained with haematoxylin and eosin (H&E) and sent for pathological analysis of tissue quality and signs of thermal damage.

Results

No significant changes in the pigs’ local temperature were observed after bone drilling with a battery-powered drill device. Across all measurements, the median change in temperature between the initial measurement and the temperature measured after drilling (at 20 s) was 0.1 °C. Histological examination of the bone core specimens revealed no signs of mechanical or thermal damage.

Conclusion

Overall, this preliminary study shows that battery-powered, drill-assisted harvesting of bone core specimens does not appear to cause mechanical or thermal damage.
Implementierung eines sektorenübergreifenden Gesamtversorgungskonzeptes
Authors: Purwins Daniel , Roes Martina
Published: August 2021

Hintergrund

Aufgrund einer gestiegenen Nachfrage nach ambulanten Leistungen von älteren Menschen aus der unmittelbaren Nähe zu seinen stationären Pflegeeinrichtungen erweiterte ein Träger sein (teil-)stationäres Pflegeangebot um ambulante Leistungen. Für die Realisierung einer solchen strategischen Neuausrichtung kommt es neben einer Orientierung an dem Wandlungsbedarf und der Wandlungsfähigkeit insbesondere auf die Wandlungsbereitschaft der Mitarbeiter des Trägers an.

Ziel der Sekundärdatenanalyse

Identifikation von Faktoren, welche den Wandlungsbedarf, die Wandlungsfähigkeit und die Wandlungsbereitschaft der Mitarbeiter beeinflusst haben. Der Fokus dieses Artikels liegt auf der Wandlungsbereitschaft der Mitarbeiter.

Material und Methoden

Basierend auf 32 leitfadengestützten (Einzel- bzw. Fokusgruppen‑)Interviews, die im Zeitraum von 2016 bis 2018 zu 3 verschiedenen Zeitpunkten mit 3 verschiedenen Mitarbeitergruppen des Trägers geführt wurden, erfolgte eine Sekundärdatenanalyse mittels inhaltlich-strukturierender qualitativer Inhaltsanalyse.

Ergebnisse

Die Wandlungsbereitschaft der Mitarbeiter wurde durch folgende Faktoren beeinflusst: Die situationsunabhängige Veränderungsbereitschaft, die bewusste Entscheidung für das stationäre Setting, die Idee des Gesamtversorgungskonzeptes (GVK), die Umsetzung des GVK, die Leistungsempfänger, sowie Vorerfahrungen in der ambulanten Pflege.

Diskussion

Die Ergebnisse bieten Einblicke dahingehend, welche Faktoren die Wandlungsbereitschaft von Mitarbeitern beeinflusst haben und, bezogen auf die Ausgestaltung vergleichbarer Veränderungsprozesse, zu berücksichtigen sind.
Measurements of transepithelial electrical resistance (TEER) are affected by junctional length in immature epithelial monolayers
Authors: Felix Kannapin , Tobias Schmitz , Jan Hansmann , Nicolas Schlegel , Michael Meir
Published: August 2021

The measurement of transepithelial electrical resistance (TEER) is a common technique to determine the barrier integrity of epithelial cell monolayers. However, it is remarkable that absolute TEER values of similar cell types cultured under comparable conditions show an immense heterogeneity. Based on previous observations, we hypothesized that the heterogeneity of absolute TEER measurements can not only be explained by maturation of junctional proteins but rather by dynamics in the absolute length of cell junctions within monolayers. Therefore, we analyzed TEER in epithelial cell monolayers of Caco2 cells during their differentiation, with special emphasis on both changes in the junctional complex and overall cell morphology within monolayers. We found that in epithelial Caco2 monolayers TEER increased until confluency, then decreased for some time, which was then followed by an additional increase during junctional differentiation. In contrast, permeability of macromolecules measured at different time points as 4 kDA fluorescein isothiocyanate (FITC)-dextran flux across monolayers steadily decreased during this time. Detailed analysis suggested that this observation could be explained by alterations of junctional length along the cell borders within monolayers during differentiation. In conclusion, these observations confirmed that changes in cell numbers and consecutive increase of junctional length have a critical impact on TEER values, especially at stages of early confluency when junctions are immature.
Recontacting in medical genetics: the implications of a broadening knowledge base
Authors: Doheny Shane
Published: August 2021

The practice of recontacting patients has a long history in medicine but emerged as an issue in genetics as the rapid expansion of knowledge and of testing capacity raised questions about whether, when and how to recontact patients. Until recently, the debate on recontacting has focussed on theoretical concerns of experts. The publication of empirical research into the views of patients, clinicians, laboratories and services in a number of countries has changed this. These studies have filled out, and altered our view of, this issue. Whereas debates on the duty to recontact have explored all aspects of recontact practice, recent contributions have been developing a more nuanced view of recontacting. The result is a narrowing of the scope of the duty, so that a norm on recontacting focuses on the practice of reaching out to discharged patients. This brings into focus the importance of the consent conversation, the resource implications of this duty, and the role of the patient in recontacting.
Using machine learning to model the training scalability of convolutional neural networks on clusters of GPUs
Authors: Barrachina Sergio , Castelló Adrián , Catalán Mar , Dolz Manuel F. , Mestre Jose I.
Published: August 2021

In this work, we build a general piece-wise model to analyze data-parallel (DP) training costs of convolutional neural networks (CNNs) on clusters of GPUs. This general model is based on i) multi-layer perceptrons (MLPs) in charge of modeling the NVIDIA cuDNN/cuBLAS library kernels involved in the training of some of the state-of-the-art CNNs; and ii) an analytical model in charge of modeling the NVIDIA NCCL Allreduce collective primitive using the Ring algorithm. The CNN training scalability study performed using this model in combination with the Roofline technique on varying batch sizes, node (floating-point) arithmetic performance, node memory bandwidth, network link bandwidth, and cluster dimension unveil some crucial bottlenecks at both GPU and cluster level. To provide evidence of this analysis, we validate the accuracy of the proposed model against a Python library for distributed deep learning training.
Depression, anxiety, and stress in oral lichen planus: a systematic review and meta-analysis
Authors: De Porras-Carrique Teresa , González-Moles Miguel Ángel , Warnakulasuriya Saman , Ramos-García Pablo
Published: August 2021

Objectives

We present this systematic review and meta-analyses to evaluate current evidence on the prevalence of depression, anxiety, and stress in patients with oral lichen planus and their magnitude of association.

Material and methods

We searched PubMed, Embase, Web of Science, Scopus, PsycInfo, and Google Scholar for studies published before January 2021. We evaluated the quality of studies using a specific method for systematic reviews addressing prevalence questions, designed by the Joanna Briggs Institute. We carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses.

Results

Fifty-one studies (which recruited 6,815 patients) met the inclusion criteria. Our results reveal a high prevalence of depression (31.19%), anxiety (54.76%), and stress (41.10%) in oral lichen planus. Furthermore, OLP patients presented a significantly higher relative frequency than control group without OLP for depression (OR = 6.15, 95% CI = 2.73–13.89, p < 0.001), anxiety (OR = 3.51, 95% CI = 2.10–5.85, p < 0.001), and stress (OR = 3.64, 95% CI = 1.48–8.94, p = 0.005), showing large effect sizes. Subgroups meta-analyses showed the relevance of the participation of psychologists and psychiatrists in the diagnosis of depression, anxiety, and stress in patients with OLP. Multivariable meta-regression analysis showed the importance of the comorbidity of depression-anxiety in patients with OLP.

Conclusions

Our systematic review and meta-analysis show that patients with OLP suffer a higher prevalence of depression, anxiety, and stress, being more frequent than in general population.

Clinical relevance

In the dental clinic, especially dentists should be aware of depression, anxiety, and stress in OLP patients to achieve a correct referral.
Phosphorus removal in denitrifying woodchip bioreactors varies by wood type and water chemistry
Authors: Sanchez Bustamante-Bailon Ana Paula , Margenot Andrew , Cooke Richard A. C. , Christianson Laura E.
Published: August 2021

Denitrifying woodchip bioreactors are a practical nitrogen (N) mitigation technology but evaluating the potential for bioreactor phosphorus (P) removal is highly relevant given that (1) agricultural runoff often contains N and P, (2) very low P concentrations cause eutrophication, and (3) there are few options for removing dissolved P once it is in runoff. A series of batch tests evaluated P removal by woodchips that naturally contained a range of metals known to sorb P and then three design and environmental factors (water matrix, particle size, initial dissolved reactive phosphorus (DRP) concentration). Woodchips with the highest aluminum and iron content provided the most dissolved P removal (13±2.5 mg DRP removed/kg woodchip). However, poplar woodchips, which had low metals content, provided the second highest removal (12±0.4 mg/kg) when they were tested with P-dosed river water which had a relatively complex water matrix. Chemical P sorption due to woodchip elements may be possible, but it is likely one of a variety of P removal mechanisms in real-world bioreactor settings. Scaling the results indicated bioreactors could remove 0.40 to 13 g DRP/ha. Woodchip bioreactor dissolved P removal will likely be small in magnitude, but any such contribution is an added-value benefit of this denitrifying technology.
Mechanical programming of arterial smooth muscle cells in health and ageing
Authors: Johnson Robert T. , Solanki Reesha , Warren Derek T.
Published: August 2021

Arterial smooth muscle cells (ASMCs), the predominant cell type within the arterial wall, detect and respond to external mechanical forces. These forces can be derived from blood flow (i.e. pressure and stretch) or from the supporting extracellular matrix (i.e. stiffness and topography). The healthy arterial wall is elastic, allowing the artery to change shape in response to changes in blood pressure, a property known as arterial compliance. As we age, the mechanical forces applied to ASMCs change; blood pressure and arterial wall rigidity increase and result in a reduction in arterial compliance. These changes in mechanical environment enhance ASMC contractility and promote disease-associated changes in ASMC phenotype. For mechanical stimuli to programme ASMCs, forces must influence the cell’s load-bearing apparatus, the cytoskeleton. Comprised of an interconnected network of actin filaments, microtubules and intermediate filaments, each cytoskeletal component has distinct mechanical properties that enable ASMCs to respond to changes within the mechanical environment whilst maintaining cell integrity. In this review, we discuss how mechanically driven cytoskeletal reorganisation programmes ASMC function and phenotypic switching.
Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer
Authors: Li Hong , Gao Yizhi , Ren Chenchen
Published: August 2021

Focal adhesion kinase (FAK) activation has been reported to be associated with cell progression and metastasis in a wide variety of cancer cells. Target treatment by inhibiting FAK has achieved remarkable effects in several cancers, but the effect in ovarian cancer has not been reported. In this study, we determined the role and the underlying molecular mechanism of BI853520, a novel small chemical FAK inhibitor against ovarian cancer. Results show that phosphorylated FAK tyrosine 397 (p-FAK Y397) is highly expressed in ovarian cancer tumor tissues and cell lines (SKOV3 and OVCAR3). BI853520 treatment greatly suppresses cell proliferation, viability, migration, invasion, decreases anchorage-independent growth and motility in vitro. Besides, treatment with BI853520 increases biologic effects following combination with chemotherapy in ovarian cancer cell lines. In addition, BI853520 suppresses EMT in ovarian cancer cell lines. Mechanically, BI853520 treatment downregulates the activation of PI3K/AKT/mTOR signal pathway. Finally, mice model experiments confirm BI853520 treatment dramatically reduces tumor growth in vivo and suppresses the activation of PI3K/AKT/mTOR signal pathway. Taken together, our findings demonstrate that focal adhesion kinase inhibitor BI853520 inhibits cell proliferation, migration, invasion and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer, and BI853520 can offer a preclinical rationale for targeting repression of FAK in ovarian cancer.
A box, a trough and marbles: How the Reed-Frost epidemic theory shaped epidemiological reasoning in the 20th century
Authors: Engelmann Lukas
Published: August 2021

The article takes the renewed popularity and interest in epidemiological modelling for Covid-19 as a point of departure to ask how modelling has historically shaped epidemiological reasoning. The focus lies on a particular model, developed in the late 1920s through a collaboration of the former field-epidemiologists and medical officer, Wade Hampton Frost, and the biostatistician and population ecologist Lowell Reed. Other than former approaches to epidemic theory in mathematical formula, the Reed-Frost epidemic theory was materialised in a simple mechanical analogue: a box with coloured marbles and a wooden trough. The article reconstructs how the introduction of this mechanical model has reshaped epidemiological reasoning by shifting the field from purely descriptive to analytical practices. It was not incidental that the history of this model coincided with the foundation of epidemiology as an academic discipline, as it valorised and institutionalised new theoretical contributions to the field. Through its versatility, the model shifted the field’s focus from mono-causal explanations informed by bacteriology, eugenics or sanitary perspectives towards the systematic consideration of epidemics as a set of interdependent and dynamic variables.
›Grazie‹, charis, Gabe
Authors: Mainberger Sabine
Published: August 2021

Die barocke grâce bildet die sozio-politische und ökonomische Kontrastfolie für das ideale Griechenland, das Winckelmann als Gesellschaft im Zeichen der charis entwirft. Es entspricht avant la lettre der Gaben tauschenden Gesellschaft im Sinne von Marcel Mauss. Der Begriff der charis deckt sich, wie an Pindar, einer entscheidenden Referenz des Gelehrten, deutlich ist, in vielen Hinsichten mit dem der Gabe. Winckelmann entwickelt Aspekte der charis und der Gabenbeziehung an der griechischen Lebensweise, den antiken Kunstwerken und der Kunstbetrachtung und konzipiert ›Grazie‹ als Verhältnis der Anerkennung. Seine Statuenbeschreibungen fungieren selbst als Gaben, die eine neue Art der Sozialität ermöglichen. Denn ein zeitgenössisches Pendant zu einer Gesellschaft, in der Schönheit ein fait social total bildet, ist die amikale Gemeinschaft der ästhetisch Sensibilisierten: In ihr kultivieren Gleichrangige einen liebend-vertrauten Umgang mit den Kunstwerken.
Aufwärtskompatibel? Zur Bedeutung struktureller und doktrinärer Nationalismen für die digitale Konstellation
Authors: Schünemann Wolf J.
Published: August 2021

Der Beitrag unternimmt den Versuch, theoretische Ansätze der Nationalismusforschung auf die digitale Konstellation zu übertragen. Lassen sich konstitutive Merkmale der digitalen Konstellation und aktuelle digitalpolitische Entwicklungen unter Rückgriff auf Nationalismustheorien erklären? Erweisen sich Nationalismen, denen eine Hauptfunktion bei der Integration prädigitaler Sozialräume und dem Aufbau einer politischen Weltordnung zugekommen ist, damit gleichsam als aufwärtskompatibel? Um die Beharrungskraft (nicht die Ursprünge) des Nationalen in der digitalen Konstellation zu erklären, stützt sich der Beitrag zunächst auf Ansätze konstruktivistischer Nationalismustheorie. Den Grundstein des Modells bilden strukturelle Nationalismen, verstanden als unideologische, unbewusste und vielfach unauffällige Denk- und Reproduktionsweisen des Nationalen. Diese bieten Anknüpfungspunkte für doktrinäre Nationalismen, die die Autonomie nationaler Gesellschaften thematisieren und ihre Bewahrung zur politischen Zielsetzung erheben. Aus der Kombination lassen sich aktuelle digitalpolitische Entwicklungen erklären. Zwecks empirischer Illustration der verschränkten Mechanismen (strukturell und doktrinär) fokussiert der Beitrag nacheinander auf drei digitalpolitische Handlungs- und Problemfelder: die Verwaltung kritischer Ressourcen am Beispiel des Domain-Name-Systems (DNS), die Cybersicherheitspolitik im Hinblick auf den Schutz kritischer Infrastrukturen sowie schließlich die Bekämpfung von Desinformationskampagnen durch die Regulierung von Kommunikationsströmen.
COVID-19: potential therapeutics for pediatric patients
Authors: Younis Nour K. , Zareef Rana O. , Fakhri Ghina , Bitar Fadi , Eid Ali H. , Arabi Mariam
Published: August 2021

The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder clinical symptoms are often experienced by them. Only a minimal proportion of the affected patients may develop severe and complicated COVID-19. Supportive treatment is recommended in all patients. Antiviral and immunomodulatory medications are spared for hospitalized children with respiratory distress or severe to critical disease. Up till now, remdesivir is the only USFDA-approved anti-COVID-19 medication indicated in the majority of symptomatic patients with moderate to severe disease. Dexamethasone is solely recommended in patients with respiratory distress maintained on oxygen or ventilatory support. The use of these medications in pediatric patients is founded on evidence deriving from adult studies. No randomized controlled trials (RCTs) involving pediatric COVID-19 patients have assessed these medications’ efficacy and safety, among others. Similarly, three novel monoclonal anti-SARS-CoV-2 spike protein antibodies, bamlanivimab, casirivimab and imdevimab, have been recently authorized by the USFDA. Nonetheless, their efficacy has not been demonstrated by multiple RCTs. In this review, we aim to dissect the various potential therapeutics used in children with COVID-19. We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the studied therapeutics. Our review offers an efficient and practical guide for treating children with COVID-19.
Endogenous estrogens—breast cancer and chemoprevention
Authors: Starek-Świechowicz Beata , Budziszewska Bogusława , Starek Andrzej
Published: August 2021

Breast cancer is the most common female malignancy and the second leading cause of cancer related deaths. It is estimated that about 40% of all cancer in women is hormonally mediated. Both estrogens and androgens play critical roles in the initiation and development of breast cancer. Estrogens influence normal physiological growth, proliferation, and differentiation of breast tissues, as well as the development and progression of breast malignancy. Breast cancer is caused by numerous endo- and exogenous risk factors. The paper presents estrogen metabolism, in particular 17β-estradiol and related hormones. The mechanisms of estrogen carcinogenesis include the participation of estrogen receptors, the genotoxic effect of the estrogen metabolites, and epigenetic processes that are also presented. The role of reactive oxygen species in breast cancer has been described. It called attention to a role of numerous signaling pathways in neoplastic transformation. Chemoprotective agents, besides other phytoestrogens, classical antioxidants, synthetic compounds, and their mechanisms of action have been shown.
The hairpin extension controls solvent access to the chromophore binding pocket in a bacterial phytochrome: a UV–vis absorption spectroscopy study
Authors: Rumfeldt Jessica , Kurttila Moona , Takala Heikki , Ihalainen Janne A.
Published: August 2021

Solvent access to the protein interior plays an important role in the function of many proteins. Phytochromes contain a specific structural feature, a hairpin extension that appears to relay structural information from the chromophore to the rest of the protein. The extension interacts with amino acids near the chromophore, and hence shields the chromophore from the surrounding solvent. We envision that the detachment of the extension from the protein surface allows solvent exchange reactions in the vicinity of the chromophore. This can facilitate for example, proton transfer processes between solvent and the protein interior. To test this hypothesis, the kinetics of the protonation state of the biliverdin chromophore fromDeinococcus radioduransbacteriophytchrome, and thus, the pH of the surrounding solution, is determined. The observed absorbance changes are related to the solvent access of the chromophore binding pocket, gated by the hairpin extension. We therefore propose a model with an “open” (solvent-exposed, deprotonation-active on a (sub)second time-scale) state and a “closed” (solvent-gated, deprotonation inactive) state, where the hairpin fluctuates slowly between these conformations thereby controlling the deprotonation process of the chromophore on a minute time scale. When the connection between the hairpin and the biliverdin surroundings is destabilized by a point mutation, the amplitude of the deprotonation phase increases considerably. In the absence of the extension, the chromophore deprotonates essentially without any “gating”. Hence, we introduce a straightforward method to study the stability and fluctuation of the phytochrome hairpin in its photostationary state. This approach can be extended to other chromophore-protein systems where absorption changes reflect dynamic processes of the protein.
Global Spatial Distribution of Dipolarization Fronts in the Saturn's Magnetosphere: Cassini Observations
Authors: Xu S. B. , Huang S. Y. , Yuan Z. G. , Deng X. H. , Jiang K. , Wei Y. Y. , Zhang J. , Zhang Z. H. , Xiong Q. Y. , Yu L. , Lin R. T. , Waite J. H.
Published: August 2021

Dipolarization front (DF), characterized by a sharp increase of the south‐north component of the magnetic field, is suggested to play an important role in transferring plasmas, magnetic fluxes, and energy in the planetary magnetosphere. Using the measurements from the Cassini spacecraft between January 1, 2005 and June 15, 2011, we successfully selected 96 DF events, and obtained the global spatial distribution of DFs in the Saturn's magnetosphere. For the first time, we found that DFs are distributed not only in the nightside magnetotail but also in the dayside magnetosphere. The dayside DF events are mainly located from X = 10 RS to X = 30 RS (RS is the Saturn's radius) while the nightside events have a wide range, up to X∼−50 RS. Moreover, the DFs are observed to be asymmetric in the south‐northern hemisphere: ∼70% of events in the northern hemisphere and ∼30% of events in the southern hemisphere, which is likely to be due to the asymmetric orbit coverage of the Cassini in south‐northern hemisphere. The occurrence of dayside DFs provides a strong evidence that the magnetic reconnection could also occur in the dayside of Saturn's magnetosphere. Thus, our results concerning the location and distribution of DFs are helpful for the study of the site of magnetic reconnection and energy transport/dissipation in Saturn's magnetosphere.
Mercury's Crustal Thickness and Contractional Strain
Authors: Watters Thomas R. , James Peter B. , Selvans Michelle M.
Published: August 2021

The crust of Mercury has experienced contraction on a global scale. Contractional deformation is expressed by a broadly distributed network of lobate thrust fault scarps. The most likely principal source of stress is global contraction from cooling of Mercury's interior. Global contraction alone would be expected to result in a uniformly distributed population of thrust faults. Mercury's fault scarps, however, often occur in long, linear clusters or bands. An analysis of the contractional strain as a function of crustal thickness, estimated in two crustal thickness models (CT1 and CT2) derived from gravity and topography data obtained during the MESSENGER mission, indicates the greatest contractional strain occurs in crust 50–60 km thick. On Earth, mantle downwelling can thicken and compress overlying crust, regionally concentrating thrust faults. Clusters of lobate scarps collocated with regions of thick crust suggest downward mantle flow contributed to the localization of lithosphere‐penetrating thrust faults.
Interpreting the Dependence of Cloud‐Radiative Adjustment on Forcing Agent
Authors: Salvi Pietro , Ceppi Paulo , Gregory Jonathan M.
Published: August 2021

Effective radiative forcing includes a contribution by rapid adjustments, that is, changes in temperature, water vapor, and clouds that modify the energy budget. Cloud adjustments in particular have been shown to depend strongly on forcing agent. We perform idealized atmospheric heating experiments to demonstrate a relationship between cloud adjustment and the vertical profile of imposed radiative heating: boundary‐layer heating causes a positive cloud adjustment (a net downward radiative anomaly), while free‐tropospheric heating yields a negative adjustment. This dependence is dominated by the shortwave effect of changes in low clouds. Much of the variation in cloud adjustment among common forcing agents such as , , solar forcing, and black carbon is explained by the “characteristic altitude” (i.e., the vertical center‐of‐mass) of their heating profiles, through its effect on tropospheric stability.
Multiple Metrics Informed Projections of Future Precipitation in China
Authors: Wang Lei , Qian Yun , Leung L. Ruby , Chen Xiaodong , Sarangi Chandan , Lu Jian , Song Fengfei , Gao Yang , Lin Guangxing , Zhang Yaocun
Published: August 2021

Predicting how regional precipitation will respond to future warming is among the most challenging undertaking in climate change projection. Despite sustained efforts to improve modeling and understanding of precipitation, the overall uncertainty in projecting regional precipitation has not been reduced substantially. Here, the potential for more robust precipitation projections is demonstrated through the use of discriminating metrics to subsample a multimodel ensemble. Using a two‐dimensional metric of precipitation and its relationship with large‐scale circulation indices in East Asia, 31 models in the Coupled Model Intercomparison Project Phase 5 (CMIP5) are classified into three groups. Models in the top performing group projected statistically significant increasing trends in precipitation and the regional precipitation patterns are more similar to each other than to the patterns in the bottom performing group. In contrast, models in the bottom performing group projected diverse responses, with overall small drying or no significant trends in precipitation.
Phylogenetic Underpinning of Groundwater Use by Trees
Authors: Knighton James , Fricke Evan , Evaristo Jaivime , de Boer Hugo Jan , Wassen Martin Joseph
Published: August 2021

Root water uptake (RWU) strategies shape climate‐vegetation feedbacks and ecosystem productivity. A fundamental relationship between RWU strategies and evolutionary histories (phylogeny) of trees, however, remains poorly understood. Establishing a phylogenetic basis for tree RWU, particularly groundwater use, could improve their representation in terrestrial biosphere models (TBMs) that are crucial for understanding hydrologic and ecosystem responses to climate perturbations. We explored possible phylogenetic bases for tree RWU using two independent data sets: (a) observed root and local groundwater depths representing 502 tree species, and (b) groundwater, soil, and xylem water isotopic evidence for groundwater uptake representing 412 species. Maximum rooting depths (RDMAX), the ratio between RDMAX and mean water table depth (WT) (RDMAX/WT), and isotopic evidence of groundwater uptake showed significant phylogenetic signals, suggesting that tree RWU strategies are more similar among closely related species. Our findings may be used to parameterize species‐level RWU in TBMs, particularly for data‐poor regions.
The “Hockey Stick” Imprint in Northwest African Speleothems
Authors: Sha Lijuan , Brahim Yassine Ait , Wassenburg Jasper A. , Yin Jianjun , Lu Jiayu , Cruz Francisco W. , Cai Yanjun , Edwards R. Lawrence , Cheng Hai
Published: August 2021

We present absolutely dated speleothem δ18O records spanning the past ∼1.5 kyr, which provide new evidence of the transmission of an anthropogenic signal to natural climatic archives in NW Africa. Combined with three other speleothem δ18O records from SW Morocco, the results indicate unprecedentedly dry conditions during the 20th century, which developed more rapidly than those during the Medieval Climate Anomaly (900–1350 CE), likely due to rising atmospheric CO2 levels. The 20th century drying evident in the speleothem records is consistent with the “Hockey Stick” pattern of increasing temperatures due to global warming. We demonstrate that this rapid drying is linked to warmer sea surface temperatures (SSTs) over the Azores High region, and cooler local SSTs off the coast of NW Africa. These changes intensified the Canary Current Upwelling, which promoted increased biological productivity in the surface water and enhanced the coastal fishing industry in Morocco.