bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of immunosurveillance and distant metastases in colorectal cancer
Authors: Jacob Sven , Jurinovic Vindi , Lampert Christopher , Pretzsch Elise , Kumbrink Jörg , Neumann Jens , Haoyu Ren , Renz Bernhard W. , Kirchner Thomas , Guba Markus O. , Werner Jens , Angele Martin K. , Bösch Florian
Published: September 2021

Background

Colorectal cancer (CRC) is the third most common malignancy worldwide, but the key driver to distant metastases is still unknown. This study aimed to elucidate the link between immunosurveillance and organotropism of metastases in CRC by evaluating different gene signatures and pathways.

Material and methods

CRC patients undergoing surgery at the Department of General, Visceral and Transplantation Surgery at the Ludwig-Maximilian University Hospital Munich (Munich, Germany) were screened and categorized into M0 (no distant metastases), HEP (liver metastases) and PER (peritoneal carcinomatosis) after a 5-year follow-up. Six patients of each group were randomly selected to conduct a NanoString analysis, which includes 770 genes. Subsequently, all genes were further analyzed by gene set enrichment analysis (GSEA) based on seven main cancer-associated databases.

Results

Comparing HEP vs. M0, the gene set associated with the Toll-like receptor (TLR) cascade defined by the Reactome database was significantly overrepresented in HEP. HSP90B1, MAPKAPK3, PPP2CB, PPP2R1A were identified as the core enrichment genes. The immunologic signature pathway GSE6875_TCONV_VS_FOXP3_KO_TREG_DN with FOXP3 as downstream target was significantly overexpressed in M0. RB1, TMEM 100, CFP, ZKSCAN5, DDX50 were the core enrichment genes. Comparing PER vs. M0 no significantly differentially expressed gene signatures were identified.

Conclusion

Chronic inflammation might enhance local tumor growth. This is the first study identifying immune related gene sets differentially expressed between patients with either liver or peritoneal metastases. The present findings suggest that the formation of liver metastases might be associated with TLR-associated pathways. In M0, a high expression of FOXP3 + tumor infiltrating lymphocytes (TILs) seemed to prevent at least in part metastases. Thus, these correlative findings lay the cornerstone to further studies elucidating the underlying mechanisms of organotropism of metastases.
Anthocyanin synthesis potential in betalain-producing Caryophyllales plants
Authors: Sakuta Masaaki , Tanaka Asuka , Iwase Kaori , Miyasaka Mizuki , Ichiki Sachiko , Hatai Miho , Inoue Yoriko T. , Yamagami Ayumi , Nakano Takeshi , Yoshida Kazuko , Shimada Setsuko
Published: September 2021

Although anthocyanins are widely distributed in higher plants, betalains have replaced anthocyanins in most species of the order Caryophyllales. The accumulation of flavonols in Caryophyllales plants implies that the late step of anthocyanin biosynthesis from dihydroflavonols to anthocyanins may be blocked in Caryophyllales. The isolation and characterization of functional dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS) from Caryophyllales plants has indicated a lack of anthocyanins due to suppression of DFR and ANS. In this study, we demonstrated that overexpression of DFR and ANS from Spinacia oleracea (SoDFR and SoANS, respectively) with PhAN9, which encodes glutathione S-transferase (required for anthocyanin sequestration) from Petunia induces ectopic anthocyanin accumulation in yellow tepals of the cactus Astrophytum myriostigma. A promoter assay of SoANS showed that the Arabidopsis MYB transcription factor PRODUCTION OF ANTHOCYANIN PIGMENT1 (PAP1) activated the SoANS promoter in Arabidopsis leaves. The overexpression of Arabidopsis transcription factors with PhAN9 also induced ectopic anthocyanin accumulation in yellow cactus tepals. PAP homologs from betalain-producing Caryophyllales did not activate the promoter of ANS. In-depth characterization of Caryophyllales PAPs and site-directed mutagenesis in the R2R3–MYB domains identified the amino acid residues affecting transactivation of Caryophyllales PAPs. The substitution of amino acid residues recovered the transactivation ability of Caryophyllales PAPs. Therefore, loss of function in MYB transcription factors may suppress expression of genes involved in the late stage of anthocyanin synthesis, resulting in a lack of anthocyanin in betalain-producing Caryophyllales plants.
Rapid return to normal activities at a residential summer camp during the COVID-19 pandemic
Authors: Klunk A. , Holloway R. , Babaoff A. , Jelin E. B.
Published: September 2021

Aim

Infection prevention and control (IPC) within residential settings is a central focus of the coronavirus disease 2019 (COVID-19) pandemic. Youth residential summer camps are an excellent model for such environments and have thus far had mixed results. The aim of this report was to describe the successful implementation of a seven-week overnight summer camp with rapid return to normal activities from June to August 2020.

Subjects and methods

This retrospective study included 427 individuals who traveled from 24 US states. All staff and campers were tested by serial nasopharyngeal PCR tests in the context of strict infection prevention and control (IPC) measures, including cohorts and masking. The entire camp population was isolated from non-camp personnel with special measures for food, supply, and mail delivery.

Results

During the two-week staff session, one staff member tested positive for SARS-CoV-2, was isolated, and sent safely off premises. All other campers and staff had three negative PCR tests: 1–8 days before arrival, upon arrival, and 5–6 days after arrival. After these three negative tests, 6 days into camp, most IPCs, including masking, were successfully lifted and a normal camp experience was possible.

Conclusions

These findings indicate that serial PCR-based testing and strict adherence to IPC measures among cohorts can allow for successful assumption of near normal group activities in a residential setting during the COVID-19 pandemic. This result at an overnight summer camp has broad implications for similar residential communities such as boarding schools, other youth education and development programs, as well as nursing homes and military installations.
Predictive Association of Low- and High-Fidelity Supported Employment Programs with Multiple Outcomes in a Real-World Setting: A Prospective Longitudinal Multi-site Study
Authors: Yamaguchi Sosei , Sato Sayaka , Shiozawa Takuma , Matsunaga Asami , Ojio Yasutaka , Fujii Chiyo
Published: September 2021

Purpose

The individual placement and support (IPS) model of supported employment is a leading evidence-based practice in community mental health services. In Japan, individualized supported employment that is highly informed by the philosophy of the IPS model has been implemented. While there is a body of evidence demonstrating the association between program fidelity and the proportion of participants gaining competitive employment, the association between fidelity and a wider set of vocational and individual outcomes has received limited investigation. This study aimed to assess whether high-fidelity individualized supported employment programs were superior to low-fidelity programs in terms of vocational outcomes, preferred job acquisition, and patient-reported outcome measures (PROMs).

Methods

A prospective longitudinal study with 24-month follow-up analyzed 16 individualized supported employment programs. The Japanese version of the individualized Supported Employment Fidelity scale (JiSEF) was used to assess the structural quality of supported employment programs (scores: low-fidelity program, ≤ 90; high-fidelity program, ≥ 91). Job acquisition, work tenure, work earnings, job preference matching (e.g., occupation type, salary, and illness disclosure), and PROMs such as the INSPIRE and WHO-Five Well-being index were compared between groups.

Results

There were 75 and 127 participants in the low-fidelity group (k = 6) and high-fidelity group (k = 10), respectively. The high-fidelity group demonstrated better vocational outcomes than the low-fidelity group, i.e., higher competitive job acquisition (71.7% versus 38.7%, respectively, adjusted odds ratio (aOR) = 3.6, p = 0.002), longer work tenure (adjusted mean difference = 140.8, p < 0.001), and better match for illness disclosure preference (92.6% versus 68.0%, respectively, aOR = 5.9, p = 0.003). However, we found no differences between groups in other preference matches or PROM outcomes.

Conclusion

High-fidelity individualized supported employment programs resulted in good vocational outcomes in a real-world setting. However, enhancing service quality to increase desired job acquisition and improve PROMs will be important in the future.

Clinical Trial Registration

UMIN000025648
Implementing Confidence Assessment in Low-Stakes, Formative Mathematics Assessments
Authors: Foster Colin
Published: September 2021

Confidence assessment (CA) involves students stating alongside each of their answers a confidence rating (e.g. 0 low to 10 high) to express how certain they are that their answer is correct. Each student’s score is calculated as the sum of the confidence ratings on the items that they answered correctly, minus the sum of the confidence ratings on the items that they answered incorrectly; this scoring system is designed to incentivize students to give truthful confidence ratings. Previous research found that secondary-school mathematics students readily understood the negative-marking feature of a CA instrument used during one lesson, and that they were generally positive about the CA approach. This paper reports on a quasi-experimental trial of CA in four secondary-school mathematics lessons (N = 475 students) across time periods ranging from 3 weeks up to one academic year, compared to business-as-usual controls. A meta-analysis of the effect sizes across the four schools gave an aggregated Cohen’s d of –0.02 [95% CI –0.22, 0.19] and an overall Bayes Factor B01 of 8.48. This indicated substantial evidence for the null hypothesis that there was no difference between the attainment gains of the intervention group and the control group, relative to the alternative hypothesis that the gains were different. I conclude that incorporating confidence assessment into low-stakes classroom mathematics formative assessments does not appear to be detrimental to students’ attainment, and I suggest reasons why a clear positive outcome was not obtained.
One does not simply track students: the relationship between teachers’ perceived public track regard and their job satisfaction in a context of rigid tracking
Authors: Dekeyser Lorenz , Van Houtte Mieke , Maene Charlotte , A.J. Stevens Peter
Published: September 2021

Although there is a wealth of research on the educational and broader outcomes of tracking in education, there is virtually no research that investigates teachers’ track identities on such outcomes. Building on research that focuses on the determinants of teachers’ job satisfaction, tracking outcomes and social categorization theory, this study tests the relationship between the perceived public regard of a teachers’ track and their job satisfaction, in a Belgian context of within- (vocational, technical and general education tracks) and between-school tracking (multilateral versus categorical schools). Data of the Belgian SIS (School, Identity and Society)-survey, a large-scale dataset gathered in 2017, containing the self-reports of 324 teachers, clustered in 43 secondary schools is used to test particular hypotheses regarding this relationship. The results of a multilevel analysis show that the relationship between teachers’ public track regard and their job satisfaction varies according to the track they teach and whether they work in a categorical or multilateral school. The findings highlight the importance of carrying out further research on tracked identities in education.
Recommended tool compounds and drugs for blocking P2X and P2Y receptors
Authors: Müller Christa E. , Namasivayam Vigneshwaran
Published: September 2021

This review article presents a collection of tool compounds that selectively block and are recommended for studying P2Y and P2X receptor subtypes, investigating their roles in physiology and validating them as future drug targets. Moreover, drug candidates and approved drugs for P2 receptors will be discussed.
Favipiravir treatment does not influence disease progression among adult patients hospitalized with moderate-to-severe COVID-19: a prospective, sequential cohort study from Hungary
Authors: Szabo Balint Gergely , Lenart Katalin Szidonia , Petrik Borisz , Gaspar Zsofia , Kiss-Dala Noemi , Szlavik Janos , Valyi-Nagy Istvan , Lakatos Botond ,   Saint Ladislaus COVID-19 Collaborative
Published: September 2021

Data suggests that favipiravir (FVP) could be used against SARS-CoV-2. Our aim was to investigate the role of FVP in COVID-19 treatment. A prospective sequential cohort study was performed among adults hospitalized at our center between March and August 2020 with moderate-to-severe, PCR-confirmed COVID-19. For diagnosis and severity, ECDC and WHO definitions were utilized. Patients were screened for inclusion by a priori criteria and included in the FVP cohort if standard-of-care (SOC) + FVP or the non-FVP cohort if SOC ± other antivirals without FVP were administered for > 48 h from diagnosis. Treatment allocation was done per national guidelines, based on severity and drug availability. Primary endpoint was disease progression, a composite of 14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy. The impact of FVP exposure on disease progression was analyzed by binomial logistic regression. In all, 150 patients were included, 75 in each cohort. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p = 0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p = 0.8), and need for mechanical ventilation (8/75, 10.7% vs. 4/75, 5.3%, p = 0.22) were similar, while immunomodulatory therapies were required more frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p < 0.01). The use of favipiravir was not retained as a protective factor against disease progression in multivatiate analysis. Time to antiviral therapy from PCR positivity, disease severity, need for oxygen supportation, and ICU admittance rates did not differ statistically between cohorts. In this study, favipiravir did not seem to positively affect disease progression.
Betriebliche Ausbildungsqualität – Eine Frage der Perspektive?
Authors: Krötz Maximilian , Deutscher Viola
Published: September 2021

Trotz der Bedeutung der dualen Berufsausbildung für die Biografien der Absolventen sowie für die Deckung des wachsenden Fachkräftebedarfs mangelt es an multiperspektivischen Untersuchungen zur betrieblichen Ausbildungsqualität. Bisherige Studien gehen zumeist nicht über deskriptive Analysen einzelner Akteursgruppen, mehrheitlich Auszubildende, hinaus. Die wenigen multiperspektivischen Befunde indizieren dagegen, dass Qualitätseinschätzungen von Auszubildenden und Ausbildenden teils weit auseinanderliegen. Dieser Befund wird im vorliegenden Beitrag anhand von Umfragedaten (311 Auszubildende, 30 Ausbildende) auf Gruppenebene bestätigt. Zudem wird die potenzielle Bedeutung der eingenommenen Perspektive für die Modellierung von Zusammenhängen verschiedener Qualitätsdimensionen überprüft. Hierbei korreliert eine bilaterale Modellierung von Ausbildungsqualität, welche Wahrnehmungsunterschiede zwischen Auszubildenden und Ausbildenden betrachtet, signifikant stärker mit Abbruchgedanken der Auszubildenden als deren unilaterale Qualitätseinschätzung. Zudem wird gezeigt, dass bestimmte Merkmale der Auszubildenden Wahrnehmungsunterschiede der Ausbildungsqualität zwischen verschiedenen Akteuren in Teilen erklären können. Insgesamt unterstreichen die Befunde damit die Relevanz multiperspektivischer Ansätze in der Betrachtung der Ausbildungsqualität.
Introduction to Heterostructured Materials: A Fast Emerging Field
Authors: Zhu Yuntian
Published: September 2021

Strong and tough materials are desired for lightweight, energy efficient applications such as electric cars and aerospace applications. Recently, heterostructures are found to produce unprecedented strength and ductility that are considered impossible based on the materials science in our textbooks. Such superior mechanical properties are enabled by a new scientific principle: hetero-deformation-induced (HDI) strengthening and work hardening. Heterostructured (HS) materials consist of heterogeneous zones with dramatic difference (> 100 pct) in flow stresses. The inter-zone interaction produces back stress in the soft zones and forward stress in the hard zones, which collectively produces the HDI stress. HS materials possess a significant synergistic effect where the integrated property exceeds the prediction by the rule of mixtures. Importantly, HS materials can be produced by current industrial facilities at large scale and low cost. The new materials sciences and promising applications are driving the fast development of the HS materials as an emerging field. There are many fundamental issues that need to be probed so as to effectively design HS materials for superior properties. To solve these issues, it requires collaborative efforts by the communities of experimental materials science and computational material science and mechanics.
Symbiosis and the Anthropocene
Authors: Hom Erik F. Y. , Penn Alexandra S.
Published: September 2021

Recent human activity has profoundly transformed Earth biomes on a scale and at rates that are unprecedented. Given the central role of symbioses in ecosystem processes, functions, and services throughout the Earth biosphere, the impacts of human-driven change on symbioses are critical to understand. Symbioses are not merely collections of organisms, but co-evolved partners that arise from the synergistic combination and action of different genetic programs. They function with varying degrees of permanence and selection as emergent units with substantial potential for combinatorial and evolutionary innovation in both structure and function. Following an articulation of operational definitions of symbiosis and related concepts and characteristics of the Anthropocene, we outline a basic typology of anthropogenic change (AC) and a conceptual framework for how AC might mechanistically impact symbioses with select case examples to highlight our perspective. We discuss surprising connections between symbiosis and the Anthropocene, suggesting ways in which new symbioses could arise due to AC, how symbioses could be agents of ecosystem change, and how symbioses, broadly defined, of humans and “farmed” organisms may have launched the Anthropocene. We conclude with reflections on the robustness of symbioses to AC and our perspective on the importance of symbioses as ecosystem keystones and the need to tackle anthropogenic challenges as wise and humble stewards embedded within the system.
Application of regression methods for classification of sewers’ damages
Authors: Kutyłowska Małgorzata , Kowalski Dariusz
Published: September 2021

The paper presents possibilities of application of selected regression methods (classification trees, support vector machines, K-nearest neighbours, artificial networks) for classification of sewers’ damages. Operational data from the time span 2006–2011 obtained from water utility were used for deterioration analysis. On the basis of the following independent variables, the modelling was carried out: diameter, depth, year of construction, material and season of damage’s occurring. The following kinds of damages were classified: corrosion, crack, longitudinal crack, displacement, unsealing, failure, collapse. The main aim of the paper was to check if prediction methodology could be useful for classification of different kinds of sewers’ damages. The obtained results pointed out that proposed classification methods are not appropriable in quality analysis of registered damages of sewers. Moreover, it is recommended for water and sewerage companies to register types of failures using unified notation which make easier preliminary classification before applying modelling approach. The calculations were performed in Statistica 13.1 software.
Analysis of the influence of rapid filter cycle interruption on filtrate quality
Authors: Zielina M.
Published: September 2021

The article presents research carried out on a sand/anthracite filter in a water treatment plant in Cracow in the south of Poland. These studies show that shutting down the filter after only three hours of operation, setting it aside for four hours and restarting without backwashing did not cause any visible deterioration in the quality of the produced filtrate. Stopping the same filter for four hours, however, after 68 h of operation, visible deterioration in the quality of the filtrate can be observed. After a significant initial deterioration, the quality of the filtrate slowly improved and after a few hours, it reached a level comparable to that before the filter was taken out of service. This was probably the result of characteristic changes in shear stress at the boundary of the deposit and flowing water in the capillaries, which accompanied changes of filtration rate. Decrease in the removal efficiency of coarser particles lasted longer and was greater than that of finer particles. Decrease in particle removal efficiency after restarting the dirty filter was difficult to identify by turbidity measurements, but clearly identifiable by measuring suspended solid concentration and the number of coarser particles. Interrupting the operation of a rapid filter shortly after it has been backwashed should not significantly reduce its efficiency, but after prolonged operation, it may adversely affect the quality of the filtrate.
Engineering of 2D nanomaterials to trap and kill SARS-CoV-2: a new insight from multi-microsecond atomistic simulations
Authors: Khedri Mohammad , Maleki Reza , Dahri Mohammad , Sadeghi Mohammad Moein , Rezvantalab Sima , Santos Hélder A. , Shahbazi Mohammad-Ali
Published: September 2021

In late 2019, coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Spike protein is one of the surface proteins of SARS-CoV-2 that is essential for its infectious function. Therefore, it received lots of attention for the preparation of antiviral drugs, vaccines, and diagnostic tools. In the current study, we use computational methods of chemistry and biology to study the interaction between spike protein and its receptor in the body, angiotensin-I-converting enzyme-2 (ACE2). Additionally, the possible interaction of two-dimensional (2D) nanomaterials, including graphene, bismuthene, phosphorene, p-doped graphene, and functionalized p-doped graphene, with spike protein is investigated. The functionalized p-doped graphene nanomaterials were found to interfere with spike protein better than the other tested nanomaterials. In addition, the interaction of the proposed nanomaterials with the main protease (Mpro) of SARS-CoV-2 was studied. Functionalized p-doped graphene nanomaterials showed more capacity to prevent the activity of Mpro. These 2D nanomaterials efficiently reduce the transmissibility and infectivity of SARS-CoV-2 by both the deformation of the spike protein and inhibiting the Mpro. The results suggest the potential use of 2D nanomaterials in a variety of prophylactic approaches, such as masks or surface coatings, and would deserve further studies in the coming years.

Graphical abstract
Update van sacrale neuromodulatie voor functiestoornissen van de lage urinewegen
Authors: Janssen Janine M. W. , Heesakkers John P. F. A. , van Koeveringe Gommert A. , Vrijens Desiree M. J. , Smits Martijn A. C.
Published: September 2021

Samenvatting

Sacrale neuromodulatie (SNM) wordt sinds de jaren 90 van de vorige eeuw toegepast als behandeling voor therapieresistente overactieve blaas of niet-obstructieve urineretentie. In dit artikel wordt het neuromodulatiesysteem, de indicaties en het werkingsmechanisme toegelicht aan de hand van de huidige inzichten en recente publicaties. Tevens worden de nieuwe ontwikkelingen op het gebied van operatietechniek, beleid rond de ingreep en het technisch aspect besproken.
Aging investigations and consideration for automotive high power lithium-ion batteries in a 48 V mild hybrid operating strategy
Authors: Geringer D. , Hofmann P. , Girard J. , Trunner E. , Knefel W.
Published: September 2021

This paper focuses on the battery aging of automotive high power lithium-ion batteries intended for 48 V mild hybrid systems. Due to a long vehicle lifetime, battery aging is of high importance, and its consideration within a hybrid system is crucial to ensure a sufficient lifetime for the battery. At the moment, only a few aging investigations and models specifically for automotive high power cells are available. Consequently, all present aging consideration methods are based on the few published aging models focusing on consumer cells. This paper describes the development of an aging model for automotive high power cells and the integration into a mild hybrid operating strategy to actively control the battery aging process during its operation. The underlying aging investigations of high-power battery cells are shown to analyze the main influences of temperature, state of charge, and C-rate. These tests are used to develop the aging model, capable of considering the main influences on the aging process. Based on this model and all gained insights, different methods for considering battery aging in a mild hybrid system are investigated. The goal is to control the aging process during operation and consequently decrease the negative influence. Two active intervention methods are developed and integrated into a 48 V mild hybrid operating strategy to validate their potential. It is possible to control the aging process and at the same time to use the insights for improving the basic hybrid powertrain design regarding reduced aging and battery costs.
A computational fluid dynamic-based method for analyzing the nonlinear relationship between windage loss and pressure in a geotechnical centrifuge
Authors: Guo Yi-Nan , Yang Yi , Yu Jun-Xiang , Ding De , Wang Ya-Lin
Published: September 2021

Temperature control is an important limitation to further increase in geotechnical centrifuge power. Although vacuum pumps can reduce windage loss, they also negatively affect heat transfer performance. Therefore, in this study, we aim to accurately determine the rate at which windage loss decreases with pressure to help assess whether reducing pressure is beneficial to temperature control. A computational fluid dynamic method based on the multi-reference model and k–ω shear-stress transport turbulence model is used to simulate the ZJU400gt geotechnical centrifuge. The windage loss and temperature of ZJU400 at 0–150 gravity acceleration under normal pressure conditions are simulated. Compared with the experimental data, the error is < 20.7%, indicating simulation reliability. Furthermore, the simulation model is used to simulate the windage loss power under low-pressure conditions and predict the relationship between the windage loss power and pressure. Compared with current calculation methods, which yield a linear relationship between windage loss and operating pressure, the simulation results indicate a slightly nonlinear relationship. At 5,000 Pa, the simulated windage loss is 40% larger than the calculated value, severely affecting the temperature control design. Moreover, the velocity exhibits minimal variation with pressure, whereas the effective kinematic viscosity varies substantially. The nonlinear relationship between the windage loss and pressure can be attributed to increased turbulent kinetic energy and the size of the wake region caused by vacuum pumping. A formula for nonlinear windage loss with pressure is proposed, providing a basis for the future design of super-gravity geotechnical centrifuges.
AENO: a Novel Reconstruction Method in Conjunction with ADER Schemes for Hyperbolic Equations
Authors: Toro Eleuterio F. , Santacá Andrea , Montecinos Gino I. , Celant Morena , Müller Lucas O.
Published: September 2021

In this paper, we present a novel spatial reconstruction scheme, called AENO, that results from a special averaging of the ENO polynomial and its closest neighbour, while retaining the stencil direction decided by the ENO choice. A variant of the scheme, called m-AENO, results from averaging the modified ENO (m-ENO) polynomial and its closest neighbour. The concept is thoroughly assessed for the one-dimensional linear advection equation and for a one-dimensional non-linear hyperbolic system, in conjunction with the fully discrete, high-order ADER approach implemented up to fifth order of accuracy in both space and time. The results, as compared to the conventional ENO, m-ENO and WENO schemes, are very encouraging. Surprisingly, our results show that the $$L_{1}$$

L
1

-errors of the novel AENO approach are the smallest for most cases considered. Crucially, for a chosen error size, AENO turns out to be the most efficient method of all five methods tested.
The Role of Micronutrients to Support Immunity for COVID-19 Prevention
Authors: Ahmed Mukhtar H. , Hassan Arez , Molnár Judit
Published: September 2021

The World Health Organization declared the novel coronavirus, named as SARS-CoV-2, as a global pandemic in early 2020 after the disease spread to more than 180 countries leading to tens of thousands of cases and many deaths within a couple of months. Consequently, this paper aims to summarize the evidence for the relationships between nutrition and the boosting of the immune system in the fight against the disease caused by SARS-CoV-2. This review, in particular, assesses the impact of vitamin and mineral supplements on the body’s defence mechanisms against SARS-CoV-2. The results revealed that there is a strong relationship between the ingestion of biological ingredients like vitamins C–E, and minerals such as zinc, and a reduction in the effects of coronavirus infection. These can be received from either nutrition rich food sources or from vitamin supplements. Furthermore, these macromolecules might have roles to play in boosting the immune response, in the healing process and the recovery time. Hence, we recommend that eating healthy foods rich in vitamins C–E with zinc and flavonoids could boost the immune system and consequently protect the body from serious infections.

Graphical Abstract
Genome of the Giant Panda Roundworm Illuminates Its Host Shift and Parasitic Adaptation
Authors: Xie Yue , Wang Sen , Wu Shuangyang , Gao Shenghan , Meng Qingshu , Wang Chengdong , Lan Jingchao , Luo Li , Zhou Xuan , Xu Jing , Gu Xiaobin , He Ran , Yang Zijiang , Peng Xuerong , Hu Songnian , Yang Guangyou
Published: September 2021

Baylisascaris schroederi, a roundworm (ascaridoid) parasite specific to the bamboo-feeding giant panda (Ailuropoda melanoleuca), represents a leading cause of mortality in wild giant panda populations. Here, we present a 293-megabase chromosome-level genome assembly of B. schroederi to infer its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential for transmission and rapid adaptation to new hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to the cuticle and basal metabolisms, indicate that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism. Additionally, we characterized the secretome of B. schroederi and predicted potential drug and vaccine targets for new control strategies. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages. Our findings on the unique biology of B. schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.
Dante's Vita Nuova and the New Testament
Authors: Franke William
Published: September 2021

Modelling knowledge as revelation and theology as poetry, this powerful new reading of the Vita nuova not only challenges Dante scholars to reconsider the book's speculative emphases but also offers the general reader an accessible yet penetrating exploration of some of the Western tradition's most far-reaching ideas surrounding love and knowledge. Dante's 'little book', included in full here in an original parallel translation, captures in its first emergence the same revolutionary ferment that would later become manifest both in the larger oeuvre of this great European writer and in the literature of the entire Western canon. William Franke demonstrates how Dante's youthful poetic autobiography disrupts sectarian thinking and reconciles the seeming contraries of divine revelation and human invention, while also providing the means for understanding religious revelation in the Bible. Ultimately, this revolutionary unification of Scripture and poetry shows the intimate working of love at the source of inspired knowing.
The Picky Eater's Recovery Book
Authors: Thomas Jennifer J. , Becker Kendra R. , Eddy Kamryn T.
Published: September 2021

Are you a picky eater? Do you worry that food will make you vomit or choke? Do you find eating to be a chore? If yes, this book is for you! Your struggles could be caused by Avoidant Restrictive Food Intake Disorder (ARFID); a disorder characterized by eating a limited variety or volume of food. You may have been told that you eat like a child, but ARFID affects people right across the lifespan, and this book is the first specifically written to support adults. Join Drs. Jennifer Thomas, Kendra Becker, and Kamryn Eddy - three ARFID experts at Harvard Medical School - to learn how to beat your ARFID at home and unlock a healthier relationship with food. Real-life examples show that you are not alone, while practical tips, quizzes, worksheets, and structured activities, take you step-by-step through the latest evidence-based treatment techniques to support your recovery.
Properties of Law
Authors: Tuori Kaarlo
Published: September 2021

Properties of Law is a legal-theoretical analysis about modern state law; about sociality, normativity and plurality as its properties, and what will come after modern state law. The main objective of this study is to offer a legal theoretical recapitulation of modern state law that avoids the fallacies of Legal Positivism. This calls for a relationist approach where law's sociality is related to normativity, and normativity to sociality. Avoiding Legal Positivism's fallacies also includes refraining from extrapolating from modern state law to law in general; replacing Legal Positivism's conceptual universalism with sensitivity to the varieties of law, and acknowledging that law existed before modern state law, that it will exist after modern state law, and that other law exists alongside modern state law. The book concludes with a discussion of the impact of digitalization on law.
A qualitative study of patients’ experiences and acceptance of computerised cognitive behavioural therapy in primary care, Scotland
Authors: Du Eliane , Quayle Ethel , Macleod Hamish
Published: September 2021

Computerised cognitive behavioural therapy (CCBT) has been made available within the National Health Service (NHS) across Scotland as an alternative treatment for mild to moderate anxiety and depression. However, the provision of CCBT services is still limited in the NHS, possibly affecting delivery of this computer-aided therapy to patients and inhibiting acceptance and uptake of this intervention. This paper reports on the qualitative exploration of patients’ experiences and acceptance of one CCBT programme delivering computer-assisted therapy (Beating the Blues: BTB), examining particularly the point of referral, access to treatment, and support. Thematic analysis was conducted on semi-structured face-to-face and email interviews with 33 patients at different NHS organisations across Scotland. Data analysis generated six key themes which illustrated patients’ experiences relating to referral and access to the treatment, and the challenges they faced: (1) information dissemination; (2) expectations and the impact of waiting for BTB; (3) impact of locations on experience of BTB; (4) preference for home access; (5) desire for better human support; and (6) desire for additional application support features. The findings highlighted that better methods of implementing and delivering such CCBT services together with the design of the technological interventions are vital to the success of these services.

Key learning aims

(1)

To understand the service models and methods of implementing and delivering one CCBT programme (BTB) in routine care;

(2)

To learn about user experiences of accessing and using BTB; and

(3)

To learn about the implications and factors that might have influenced uptake and understand the implications.
Understanding the Total Electron Content Variability Over Europe During 2009 and 2019 SSWs
Authors: Siddiqui T. A. , Yamazaki Y. , Stolle C. , Maute A. , Laštovička J. , Edemskiy I. K. , Mošna Z. , Sivakandan M.
Published: September 2021

The nature of the variability of the Total Electron Content (TEC) over Europe is investigated during 2009 and 2019 Northern Hemisphere (NH) SSW events in this study by using a combination of Global Navigation Satellite System (GNSS) based TEC observations and Thermosphere‐Ionosphere Electrodynamics General Circulation Model (TIE‐GCM) simulations. To simulate the SSW effects in TIE‐GCM, the dynamical fields from the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X) simulations of 2009 and 2019 SSWs are specified at the TIE‐GCM lower boundary. The observed and simulated TEC are in overall good agreement and therefore the simulations are used to understand the sources of mid‐latitude TEC variability during both SSWs. Through comparison of TIE‐GCM simulations with and without geomagnetic forcing, we find that the TEC variability during the 2019 SSW event, was predominantly geomagnetically forced, while for the 2009 SSW, the major variability in TEC was accounted for by the changes in vertically propagating migrating semidiurnal solar (SW2) and lunar (M2) tides. By comparing the TIE‐GCM simulations with and without the SW2 and M2 tides, we find that these semidiurnal tides contribute to 20%–25% increase in the quiet background TEC.
Telling the Stories Behind the Science
Authors: Wysession Michael
Published: September 2021

AGU’s newest journal, Perspectives of Earth and Space Scientists, is a collection of memoirs, essays, and insights that present personal perspectives on how different scientific fields have evolved.
Machine Learning Reveals Source Compositions of Intraplate Basaltic Rocks
Authors: Guo Peng , Yang Ting , Xu Wen‐Liang , Chen Bin
Published: September 2021

Recycling of crustal material is thought to introduce pyroxenite to the peridotite mantle. Mapping such lithological heterogeneity within the mantle is crucial to understanding the mantle's chemical evolution but remains challenging. By sampling the mantle source, intraplate basaltic melts provide a unique chance to reveal lithological heterogeneity within the mantle. We train machine learning (ML) models with major oxide data of experimental peridotite and pyroxenite melts to help reveal the mantle source lithology of basaltic rocks. The ML models can predict source lithologies from major oxide information with an accuracy larger than 94%. As a case study, we predict source lithology of the Cenozoic intraplate basaltic rocks in Northeast China. Our ML models suggest that pyroxenite dominates the mantle source of basaltic rocks sitting above the stagnant Pacific slab while peridotite dominates the source of the basaltic rocks located west of the slab tip, consistent with previous studies using other approaches. Our ML models could potentially be used to infer mantle source lithologies of basaltic rocks from other regions around the world.
Seasonal Variation of the D‐Region Ionosphere: Very Low Frequency (VLF) and Machine Learning Models
Authors: Richardson David K. , Cohen Morris B.
Published: September 2021

The D‐region ionosphere (6090 km) plays an important role in long‐range communication and response to solar and space weather; however, it is difficult to directly measure with currently available technology. Very low frequency (VLF) radio remote sensing is one of the more promising approaches, using the efficient reflection of VLF waves from the D‐region. A number of VLF beacons can therefore be turned into diagnostic tools. VLF remote sensing techniques are useful and can provide global coverage, but in practice have been applied to a limited area and often on only a small number of days. In this work, we expand the use of a recently introduced machine learning based approach (Gross & Cohen, 2020, https://doi.org/10.1029/2019JA027135) to observe and model the D‐region electron density using VLF transmitting beacons and receivers. We have extended the model to cover nighttime in addition to daytime, and have applied it to track D‐region waveguide parameters, h’ and , over 400 daytimes and 150 nighttimes on up to 21 transmitter‐receiver paths across the continental US. Using an exponential fit, h’ represents the height of the ionosphere and represents the slope of the electron density. Using this data set, we quantify diurnal, daily and seasonal variations of the D‐region ionosphere for both daytime and nighttime D‐region ionosphere. We show that our model identifies expected variations, as well as producing results in line with other previous studies. Additionally, we show that our daytime predictions exhibit a larger autocorrelation at higher time lags than our nighttime predictions, indicating a model with persistence may perform better.
Zircon Solubility in Solute‐Rich Supercritical Fluids and Zr Transfer From Slab to Wedge in the Deep Subduction Process
Authors: Chen Wei , Xiong Xiaolin , Takahashi Eiichi
Published: September 2021

Zircon solubility in aqueous fluids, hydrous melts, and supercritical fluids is important for understanding the high field strength elements (HFSEs) chemical transport in subduction zones. Although zircon solubility was extensively studied in aqueous fluids and hydrous silicate melts, its solubility in solute‐rich fluids or supercritical fluids is poorly known. Here, we experimentally determined zircon solubility in KAlSi3O8 (±K2O ± Al2O3) – H2O supercritical fluids at 2.0–6.0 GPa and 800°C–1000°C, close to the slab‐top conditions at sub‐arc depths. The results show that zircon solubility (expressed as ZrO2 content at zircon saturation) ranges from 65 to 6,400 ppm ZrO2, 10–100 times higher than that in dilute aqueous fluids; it increases with temperature, solute content, and solute alkalinity (molar K/Al ratio) but decreases with pressure. The experiments at 2.0 GPa show that solute alkalinity in addition to temperature and solute content exerts a primary control on zircon solubility, while the experiments at 4.0–6.0 GPa show that the negative effect of pressure on zircon solubility is offset by the increase in solute alkalinity due to the crystallization of Al‐rich phases kyanite and muscovite. We suggest that high‐alkali supercritical fluids during deep subduction could be significant transfer agents for Zr from slab to mantle wedge.
Late Oligocene–Early Miocene Detachment Faulting in Crystalline Basement, Mecca Hills, CA, Documented With Zircon (U–Th)/He Date‐eU‐Visual Radiation Damage Patterns
Authors: Moser A. C. , Ault A. K. , Stearns M. A. , Evans J. P. , Guenthner W. R.
Published: September 2021

Zircon (U–Th)/He (zircon He) thermochronometry and visual radiation damage relationships reveal the timing and patterns of Orocopia Schist and North American basement exhumation in the Mecca Hills, CA. Zircon crystals from these units were selected to maximize the spectrum in visual metamictization and effective U (eU) concentrations, and thus He retentivity, in each sample. Zircon He dates (n = 31 analyses) from six of seven samples are ∼24 Ma regardless of eU, despite a large spread in eU (>2,800 ppm) across all grains. One sample (n = 7 analyses) yields a mean ∼65 Ma date. Uniform zircon He dates over a range of eU concentrations and their preserved visual metamictization indicate these grains experienced a thermal history that induced complete He loss, but did not anneal the damage. This is consistent with recent work that indicates zircon radiation damage anneals at higher temperatures than parameterized in current damage annealing models. The zircon He data patterns, together with new zircon U‐Pb results and thermal history modeling, reveal the two basement units in the Mecca Hills exhumed simultaneously at ∼24 Ma, likely by the Orocopia Mountains detachment fault. This requires both basement units lie in the footwall of the detachment, and implies the breakaway zone of the Orocopia Mountains detachment fault was west of the present‐day Mecca Hills basement exposures and has been translated by the San Andreas fault. Combined with prior work, our data suggest large‐magnitude late Oligocene–early Miocene extension in the southwestern Cordillera was more widespread than previously recognized.
Polycythemia vera: historical oversights, diagnostic details, and therapeutic views
Authors: Tefferi Ayalew , Vannucchi Alessandro M. , Barbui Tiziano
Published: September 2021

Polycythemia vera (PV) is a relatively indolent myeloid neoplasm with median survival that exceeds 35 years in young patients, but its natural history might be interrupted by thrombotic, fibrotic, or leukemic events, with respective 20-year rates of 26%, 16%, and 4%. Current treatment strategies in PV have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression and instead are directed at preventing thrombotic complications. In the latter regard, two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). All patients require phlebotomy to keep hematocrit below 45% and once-daily low-dose aspirin, in the absence of contraindications. Cytoreductive therapy is recommended for high-risk or symptomatic low-risk disease; our first-line drug of choice in this regard is hydroxyurea but we consider pegylated interferon as an alternative in certain situations, including in young women of reproductive age, in patients manifesting intolerance or resistance to hydroxyurea therapy, and in situations where treatment is indicated for curbing phlebotomy requirement rather than preventing thrombosis. Additional treatment options include busulfan and ruxolitinib; the former is preferred in older patients and the latter in the presence of symptoms reminiscent of post-PV myelofibrosis or protracted pruritus. Our drug choices reflect our appreciation for long-term track record of safety, evidence for reduction of thrombosis risk, and broader suppression of myeloproliferation. Controlled studies are needed to clarify the added value of twice- vs once-daily aspirin dosing and direct oral anticoagulants. In this invited review, we discuss our current approach to diagnosis, prognostication, and treatment of PV in general, as well as during specific situations, including pregnancy and splanchnic vein thrombosis.