bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability and Validity of a New Computer-Based Triage Decision Support Tool: ANKUTRIAGE
Authors: Koca Ayça , Polat Onur , Oğuz Ahmet Burak , Genç Sinan , Günalp Müge , Değirmenci Soner , Tekin Deniz , Çullas Ilarslan Nisa Eda , Göktüğ Aytaç , Karakiliç Muhammed Evvah , Tanriöver Ömer Özgür , Demir Salih , Sevindik Mesut
Published: June 2022

Objective:

Triage is a tool used to determine patients’ severity of illness or injury within minutes of arrival. This study aims to assess the reliability and validity of a new computer-based triage decision support tool, ANKUTRIAGE, prospectively.

Methods:

ANKUTRIAGE, a 5-level triage tool was established considering 2 major factors, patient’s vital signs and characteristics of the admission complaint. Adult patients admitted to the ED between July and October, 2019 were consecutively and independently double triaged by 2 assessors using ANKUTRIAGE system. To measure inter-rater reliability, quadratic-weighted kappa coefficients (Kw) were calculated. For the validity, associations among urgency levels, resource use, and clinical outcomes were evaluated.

Results:

The inter-rater reliability between users of ANKUTRIAGE was excellent with an agreement coefficient (Kw) greater than 0.8 in all compared groups. In the validity phase, hospitalization rate, intensive care unit admission and mortality rate decreased from level 1 to 5. Likewise, according to the urgency levels, resource use decreased significantly as the triage level decreased (P < 0.05).

Conclusions:

ANKUTRIAGE proved to be a valid and reliable tool in the emergency department. The results showed that displaying the key discriminator for each complaint to assist decision leads to a high inter-rater agreement with good correlation between urgency levels and clinical outcomes, as well as between urgency levels and resource consumptions.
Practicing Reflexivity in International Law: Running a Never-Ending Race to Catch Up with the Western International Lawyers
Authors: Emtseva Julia
Published: June 2022

For a long time, discussions on the diversity of international legal academia and practice have not been properly addressed. Protagonists from the Global South were not even considered as relevant issue-setters of international law. However, the situation is gradually changing. More and more academics, practitioners, and students both from the Global South and Global North raise their voices to address pressing issues of discrimination, sexism, and racism that we currently observe in the international legal sphere. This article offers a glimpse into some of these challenges drawing from the author’s personal experiences. It points to existing problems of the diversity in international legal institutions, representation in international legal academia, and publishing practices. This article finally offers suggestions for how international lawyers can help each other to overcome existing inequalities and create a better environment for future generations of international legal scholars and practitioners.
CIRCE'S ETRUSCANPHARMAKA: RECONSIDERING A FRAGMENT OF AESCHYLEAN ELEGY (FR. 2 WEST)
Authors: Lightfoot Jessica
Published: June 2022

This article re-examines the sole surviving fragment of Aeschylean elegy alongside the available contextual evidence in an attempt to enhance our currently very limited understanding of Aeschylus’ elegiac output. The first section explores Theophrastus’ citation of this fragment in theHistoria Plantarumto demonstrate what we can learn about the original Aeschylean poem from its use within the later writer's discussion. The second section examines how the Italian focus of the fragment fits into a wider historical and literary discourse of interactions between Greeks and non-Greeks in the west. The third and concluding section builds on these findings to examine the possible Sicilian performance context of the original Aeschylean poem to which the fragment belongs. Ultimately the discussion demonstrates that the fragment is an important and hitherto underappreciated early witness of the development of influential cultural concepts regarding interactions between Greeks and non-Greeks in the west, and that the possibility that Aeschylus produced a poem relating to the victory of Hieron I of Syracuse over the Etruscans at Cumae in 474b.c.e.is worth serious consideration.
Trends in attitudinal acceptance of wife-beating, domestic violence, and help-seeking among married women in Nepal
Authors: Patil Vaishali P. , Khanna Sunil
Published: June 2022

This study aimed to assess the nature and magnitude of perceptions of wife-beating among women and men in Nepal and experiences of domestic violence (DV) and help-seeking among DV victims. The Nepal Demographic Health Surveys (NDHS) (2001, 2006, 2011, 2016) included questions on whether women and men justify wife-beating and whether DV victims sought help (NDHS 2011 and 2016). Covariates in regression models were guided by the socioecological model. We estimated odds ratios for dichotomous outcomes. Compiled data from Multiple Indicator Cluster Surveys was used to understand trends. About 29.1% women justified wife-beating in 2001, 24.2% in 2006, and 29.1% in 2016. About 32.4% of women experienced any DV in 2011 and 28.0% in 2016. In 2011 about 21.8% of those abused sought help and in 2016 about 25.8% sought help. Women who justified wife-beating were more likely to experience DV in 2011 (OR 5.8, p < 0.001) and in 2016 (OR 1.5, p < 0.001) and less likely to seek help in 2011 (OR 0.3, p < 0.001) and in 2016 (OR 0.8, p < 0.001). Perceptions of wife-beating play an important role in actual experiences of DV and help-seeking behavior of DV victims. Societal and individual beliefs are intertwined, and cultural norms have a great bearing on these beliefs. Both individual and wider societal-level acceptance of violence needs to be addressed simultaneously.
Carbapenem-resistant Escherichia coli from shrimp and salmon available for purchase by consumers in Canada: a risk profile using the Codex framework
Authors: Loest Daleen , Uhland F. Carl , Young Kaitlin M. , Li Xian-Zhi , Mulvey Michael R. , Reid-Smith Richard , Sherk Lauren M. , Carson Carolee A.
Published: June 2022

Resistance to carbapenems in human pathogens is a growing clinical and public health concern. The carbapenems are in an antimicrobial class considered last-resort, they are used to treat human infections caused by multidrug-resistant Enterobacterales, and they are classified by the World Health Organization as ‘High Priority Critically Important Antimicrobials’. The presence of carbapenem-resistant Enterobacterales (CREs) of animal-origin is of concern because targeted studies of Canadian retail seafood revealed the presence of carbapenem resistance in a small number of Enterobacterales isolates. To further investigate this issue, a risk profile was developed examining shrimp and salmon, the two most important seafood commodities consumed by Canadians and Escherichia coli, a member of the Enterobacterales order. Carbapenem-resistant E. coli (CREc) isolates have been identified in shrimp and other seafood products. Although carbapenem use in aquaculture has not been reported, several classes of antimicrobials are utilised globally and co-selection of antimicrobial-resistant microorganisms in an aquaculture setting is also of concern. CREs have been identified in retail seafood purchased in Canada and are currently thought to be uncommon. However, data concerning CRE or CREc occurrence and distribution in seafood are limited, and argue for implementation of ongoing or periodic surveillance.
Subjective Validity, Self-Consciousness and Inner Experience: Comments on Kraus
Authors: Sethi Janum
Published: June 2022

I raise three related objections to aspects of Katharina Kraus’s interpretation in Kant on Self-Knowledge and Self-Formation. First, I reject her claim that representations count as merely subjectively valid for Kant if they represent objects from the contingent perspective of a particular subject. I argue that Kant in fact describes consciousness of subjectively valid representations as consciousness of one’s own perceptions rather than of the objects perceived, and therefore that it plays a bigger role in his account of self-consciousness than Kraus allows. Second, whereas Kraus argues that the transcendental unity of apperception structures the content of any consciousness that is possible for a subject, I note that Kant also allows for a merely empirical unity of apperception, which he describes as in principle different from transcendental unity. Finally, I raise some worries for Kraus’s suggestion that we can be aware of the activity of thinking through inner sense.
Development and dosimetric evaluation of the IMRT prostate at outside-the-irradiated field in a heterogeneity male pelvis phantom
Authors: Jayamani J. , Osman N. D. , Tajuddin A. A. , Samson D. O. , Kamaruddin K. E. , Abdul Aziz M. Z.
Published: June 2022

Background:

Intensity-modulated radiation therapy (IMRT) treatment delivery requires pre-treatment patient-specific quality assurance (QA) for the dosimetry verification due to its complex multileaf-collimator movement. The prostate target close position between the bladder and rectum requires a tight margin during planning, and mistreatment would have a huge impact on the patient. A commercially available QA tool consists of a homogeneous medium and does not represent an exact photon interaction on the tumour and also on the nearby healthy organ.

Objective:

A heterogeneous male pelvis phantom was developed and investigated the efficiency of the treatment planning system (TPS) calculation on the off-axis region.

Methods:

Polymethyl methacrylate was used for the phantom housing, and the material closed to the bladder, rectum and prostate density was chosen to construct the organ models. The phantom was scanned and validated by the computed tomography number and density. An IMRT treatment was planned in the Monaco TPS, and a thermoluminescent dosimeter (TLD-100) was used to validate the point dosimetry. In addition, an EGSnrc Monte Carlo simulation was carried out to validate the phantom dosimetry.

Results & Discussion:

The dose measurement between TLD-100, TPS, and EGSnrc was compared and validated in the pelvis phantom. In the prostate region, the dose difference was within ± 5%, and the maximum dose difference outside-the-irradiated field was up to 20·07 % and 47·31 % in TPS and TLD-100, respectively. Meanwhile, the measured dose was lower than the calculated dose, and it was apparent for the dose outside-the-irradiated field.

Conclusion:

The developed heterogeneity male pelvis phantom was validated and verified to be an important QA device for validating radiation dosimetry in the pelvis region. The dose outside-the-irradiated field was underestimated by both TPS and TLD, respectively.
International humanitarian law-making and new military technologies
Authors: Shereshevsky Yahli
Published: June 2022

Military technology has developed rapidly in recent years, and this development challenges existing norms. It has produced countless debates about the application of international humanitarian law (IHL) to areas of war and technology including cyber military operations, military artificial intelligence (including autonomous weapons), the use of drones, and military human enhancement. Despite these rapid progressions, the prospect of creating new treaties to specifically regulate their use by militaries and in armed conflicts is very low. This is largely due to the unequal allocation of military technology among States and the differing interests that result from this inequality. The absence of formal regulation means that State and non-State actors are increasingly embracing informal means of law-making. This is similar to other areas of IHL, such as the regulation of asymmetric conflicts, where norms are contested. In such cases, State and non-State actors employ various informal law-making techniques to advance their normative positions through treaty interpretation and the identification of customary international law.

However, the discussion on military technology differs from other contemporary IHL debates. First, due to the rapid development of such technology and uncertainty about how it will be employed in practice, the interests of the various actors are less clear. Second, there are significant challenges in obtaining accurate information about new military technologies. This makes even the informal law-making path in the context of new technologies more challenging.

This paper explores the dynamics of contemporary international law-making as it relates to the regulation of new military technologies. It identifies the main techniques that are used by the relevant actors and explores the common themes among the various debates over military technology, as well as the potential specific challenges in relation to certain technologies.
Visual Translation: A Creative Tool for Practising Metacognition and Analysing Agency and Power
Authors: Swalec Jennifer
Published: June 2022

‘Visual Translation: A Creative Tool for Practising Metacognition and Analysing Agency and Power’ describes the design for a ‘visual translation’ project that I developed to help high school students in an advanced Ancient Greek literature course differentiate between literal and literary translation. This project could potentially be adapted for students at any level of Ancient Greek or Latin language studies, but would likely be particularly apt for the longer passages that are taught in intermediate and advanced language courses.
Folates in various African foods: Contents, food processing and matrix effects
Authors: Bationo Fabrice , Savadogo Boubacar , Goubgou Mahamadé
Published: June 2022

Abstract: Poor folate status is implicated in a wide variety of health disorders including megaloblastic anaemia, neural tube defects, and cardiovascular diseases. Human diet remains the main provider par excellence. Despite several public-health options to overcome this micronutrient deficiency, dietary folate intakes of women of childbearing age and children are still below recommendations in many African countries. Therefore, this review aims at presenting the current knowledge on folate contents in various African foods, and on folate losses during food processing. Seventy one food sources were evaluated in this study. These various food sources included thirty six vegetables, six cereals, height cereal products, six processed leafy vegetables, six pulses, three fruits, three legumes and three roots. All of them were originated from six African countries including Burkina Faso, Côte d’Ivoire, Egypt, Ethiopia, Nigeria, and South Africa. Folate content ranged between 11 and 73.4 μg/100 g in cereals, 1.8 and 39 μg/100 g in cereal-based processed foods, 8.48 and 48.6 μg/100 g in cooked leafy vegetables, 11.6 and 633 μg/100 g in vegetables, 10 and 22 μg/100 g in pulses, 52 and 148 μg/100 g in legumes, 8 and 106 μg/100 g in fruits. The structure of the food matrix has been shown to influence folate digestibility in foods. High bioaccessible folate, assessed by in vitro digestion, was observed among food products with dense porosity structures while low bioaccessible folate was recorded among food products with open porous structures such as porridges and some gelatinized doughs. Numerous food processing steps have also been shown to influence negatively folate contents in foods.
Notfallsonografie für Studierende
Authors: Räschle Nino , Surbeck Madlen , Walter Robin , Meienberg Andrea , Jeker Lia
Published: June 2022

Zusammenfassung. Praktische Basisfertigkeiten in der Sonografie sind seit 2018 ein obligatorischer Bestandteil der Ausbildung im Medizinstudium. Die Universitäten Basel und Bern vermitteln den Studierenden die Inhalte der POCUS-Komponente «Basis-Notfall-Sonografie» der SGUM und haben hierfür in einer Kooperation ein e-Learning «POCUS Notfallsonografie» entwickelt. Mittels dieses innovativen, als Blended Learning aufgebauten Kurskonzeptes erwerben die Studierenden so bereits im Studium Basiskenntnisse der Ultraschalldiagnostik, auf die sie in der Weiterbildung aufbauen können.
Improved Dust Representation and Impacts on Dust Transport and Radiative Effect in CAM5
Authors: Ke Ziming , Liu Xiaohong , Wu Mingxuan , Shan Yunpeng , Shi Yang
Published: June 2022

Dust transport and spatial distribution are poorly represented in current global climate models (GCMs) including the Community Atmosphere Model version 5 (CAM5). Particularly, models lack explicit representation of super‐coarse dust, which may have important implications for dust radiative forcing and impacts on biogeochemistry. A nine‐mode version of the modal aerosol model (MAM9) has been developed to address these issues. In this new aerosol scheme, four dust modes have been designed to treat dust particles of sizes up to 20 μm. The MAM9‐simulated results are compared with those from the default four‐mode version of MAM (MAM4) and also with the in situ surface measurements of dust concentration and deposition flux, satellite‐retrieved dust extinction profile, and in situ vertical measurements of dust concentrations from the NASA Atmosphere Tomography Mission (ATom). Overall, MAM9 improves the dust representation in remote regions while maintaining reasonably good results near the dust source regions. In addition, MAM9 reduces the fine dust burden and increases the coarse dust burden globally. The increased coarse dust burden has slightly increased the dust direct radiative effect by 0.01 W m−2 while it enhanced dust indirect radiative effect by 0.36 W m−2, globally.
Ocean Acidification May Drive Diatom Decline
Authors: Wright Clarissa
Published: June 2022

Diatoms contribute to global oxygen production, marine food webs, and carbon sequestration, but scientists predict that diatom populations will decline due to ocean acidification associated with climate change.
Social epidemiology of early adolescent problematic screen use in the United States
Authors: Nagata Jason M. , Singh Gurbinder , Sajjad Omar M. , Ganson Kyle T. , Testa Alexander , Jackson Dylan B. , Assari Shervin , Murray Stuart B. , Bibbins-Domingo Kirsten , Baker Fiona C.
Published: June 2022

Objective

To determine sociodemographic correlates of problematic screen use (social media, video games, mobile phones) among a racially/ethnically and socioeconomically diverse population-based sample of 10–14-year-old early adolescents.

Study design

We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018–2020; N = 8753). Multiple linear regression analyses were used to estimate associations between sociodemographic factors (age, sex, race/ethnicity, primary language, household income, parental education) and adolescent-reported problematic video game (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phone use (Mobile Phone Involvement Questionnaire).

Results

Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Having unmarried/unpartnered parents was associated with higher problematic social media use. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents (p for interaction <0.05).

Conclusions

Given the sociodemographic differences in problematic screen use, digital literacy education strategies can focus on at-risk populations, encourage targeted counseling by pediatricians, and adapt family media use plans for diverse backgrounds.

Impact

While sociodemographic differences in screen time are documented, we examined sociodemographic differences in problematic screen use in a large, diverse sample of early adolescents in the US.

Boys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use.

Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents.

Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents.

Beyond time spent on screens, pediatricians, parents, and educators should be aware of sociodemographic differences in problematic screen use.
m6A demethylase ALKBH5 is required for antibacterial innate defense by intrinsic motivation of neutrophil migration
Authors: Liu Yang , Song Renjie , Zhao Lu , Lu Zhike , Li Yini , Zhan Xinyi , Lu Fengjiao , Yang Jiang , Niu Yamei , Cao Xuetao
Published: June 2022

Neutrophil migration into the site of infection is necessary for antibacterial innate defense, whereas impaired neutrophil migration may result in excessive inflammation and even sepsis. The neutrophil migration directed by extracellular signals such as chemokines has been extensively studied, yet the intrinsic mechanism for determining neutrophil ability to migrate needs further investigation. N6-methyladenosine (m6A) RNA modification is important in immunity and inflammation, and our preliminary data indicate downregulation of RNA m6A demethylase alkB homolog 5 (ALKBH5) in neutrophils during bacterial infection. Whether m6A modification and ALKBH5 might intrinsically modulate neutrophil innate response remain unknown. Here we report that ALKBH5 is required for antibacterial innate defense by enhancing intrinsic ability of neutrophil migration. We found that deficiency of ALKBH5 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture (CLP), and Alkbh5-deficient CLP mice exhibited higher bacterial burden and massive proinflammatory cytokine production in the peritoneal cavity and blood because of less neutrophil migration. Alkbh5-deficient neutrophils had lower CXCR2 expression, thus exhibiting impaired migration toward chemokine CXCL2. Mechanistically, ALKBH5-mediated m6A demethylation empowered neutrophils with high migration capability through altering the RNA decay, consequently regulating protein expression of its targets, neutrophil migration-related molecules, including increased expression of neutrophil migration-promoting CXCR2 and NLRP12, but decreased expression of neutrophil migration-suppressive PTGER4, TNC, and WNK1. Our findings reveal a previously unknown role of ALKBH5 in imprinting migration-promoting transcriptome signatures in neutrophils and intrinsically promoting neutrophil migration for antibacterial defense, highlighting the potential application of targeting neutrophil m6A modification in controlling bacterial infections.
Natural killer cell homing and trafficking in tissues and tumors: from biology to application
Authors: Ran Guang he , Lin Yu qing , Tian Lei , Zhang Tao , Yan Dong mei , Yu Jian hua , Deng You cai
Published: June 2022

Natural killer (NK) cells, a subgroup of innate lymphoid cells, act as the first line of defense against cancer. Although some evidence shows that NK cells can develop in secondary lymphoid tissues, NK cells develop mainly in the bone marrow (BM) and egress into the blood circulation when they mature. They then migrate to and settle down in peripheral tissues, though some special subsets home back into the BM or secondary lymphoid organs. Owing to its success in allogeneic adoptive transfer for cancer treatment and its “off-the-shelf” potential, NK cell-based immunotherapy is attracting increasing attention in the treatment of various cancers. However, insufficient infiltration of adoptively transferred NK cells limits clinical utility, especially for solid tumors. Expansion of NK cells or engineered chimeric antigen receptor (CAR) NK cells ex vivo prior to adoptive transfer by using various cytokines alters the profiles of chemokine receptors, which affects the infiltration of transferred NK cells into tumor tissue. Several factors control NK cell trafficking and homing, including cell-intrinsic factors (e.g., transcriptional factors), cell-extrinsic factors (e.g., integrins, selectins, chemokines and their corresponding receptors, signals induced by cytokines, sphingosine-1-phosphate (S1P), etc.), and the cellular microenvironment. Here, we summarize the profiles and mechanisms of NK cell homing and trafficking at steady state and during tumor development, aiming to improve NK cell-based cancer immunotherapy.
Cross-feeding niches among commensal leaf bacteria are shaped by the interaction of strain-level diversity and resource availability
Authors: Murillo-Roos Mariana , Abdullah Hafiz Syed M , Debbar Mossaab , Ueberschaar Nico , Agler Matthew T
Published: June 2022

Leaf microbiomes play crucial roles in plant health, making it important to understand the origins and functional relevance of their diversity. High strain-level leaf bacterial genetic diversity is known to be relevant for interactions with hosts, but little is known about its relevance for interactions with the multitude of diverse co-colonizing microorganisms. In leaves, nutrients like amino acids are major regulators of microbial growth and activity. Using metabolomics of leaf apoplast fluid, we found that different species of the plant genus Flaveria considerably differ in the concentrations of high-cost amino acids. We investigated how these differences affect bacterial community diversity and assembly by enriching leaf bacteria in vitro with only sucrose or sucrose + amino acids as possible carbon sources. Enrichments from F. robusta were dominated by Pantoea sp. and Pseudomonas sp., regardless of carbon source. The latter was unable to grow on sucrose alone but persisted in the sucrose-only enrichment thanks to exchange of diverse metabolites from Pantoea sp. Individual Pseudomonas strains in the enrichments had high genetic similarity but still displayed clear niche partitioning, enabling distinct strains to cross-feed in parallel. Pantoea strains were also closely related, but individuals enriched from F. trinervia fed Pseudomonas more poorly than those from F. robusta. This can be explained in part by the plant environment, since some cross-feeding interactions were selected for, when experimentally evolved in a poor (sucrose-only) environment but selected against in a rich (sucrose + amino acids) one. Together, our work shows that leaf bacterial diversity is functionally relevant in cross-feeding interactions and strongly suggests that the leaf resource environment can shape these interactions and thereby indirectly drive bacterial diversity.
Combination regimen of granulocyte colony-stimulating factor and recombinant human thrombopoietin improves the curative effect on elderly patients with leukemia through inducing pyroptosis and ferroptosis of leukemia cells
Authors: Wang Xiaobin , Liu Xiaoyu , Wang Huihan
Published: June 2022

Leukemia ranks as the one of most common causes of death from tumor. 51.4% of patients with leukemia are over 65 years old. However, the median overall survival (OS) of elderly leukemia patients is less than one year. It is urgent to explore more effective treatments for elderly patients with leukemia. Our recent prospective phase II single-arm study has revealed that combination regimen of granulocyte colony-stimulating factor (G-CSF) and recombinant human thrombopoietin (rhTPO) could improve the curative effect on elderly patients with leukemia, yet the precise mechanism remains unknown. This study demonstrated that combination of G-CSF and rhTPO showed greater effect on suppressing leukemia growth than G-CSF or rhTPO alone in vitro and in vivo. Mechanistically, G-CSF induced pyroptosis through ELANE in leukemia cells. Besides, rhTPO triggered ferroptosis by EP300 in leukemia cells. Moreover, rhTPO suppressed glutathione peroxidase 4 (GPX4) expression to induce ferroptosis through blocking the interaction between EP300 and GPX4 gene promoter via associating with EP300. In summary, this study illuminated that combination regimen of G-CSF and rhTPO improved the curative effect on elderly patients with leukemia through inducing pyroptosis and ferroptosis of leukemia cells. Therefore, our results provided a theoretical basis for combination regimen of G-CSF and rhTPO treating leukemia and potential therapeutic targets for leukemia.
Transparent neural implantable devices: a comprehensive review of challenges and progress
Authors: Cho Young Uk , Lim Se Lin , Hong Jung-Hoon , Yu Ki Jun
Published: June 2022

The key to designing an implantable device lies in condensing the synergistic effects of diagnostic and therapeutic methods in a single tool. In conjunction with the integration of electrophysiology and optical modalities, a transparent neural interface alleviates challenges of conventional metal-based microelectrodes. In this review, the multimodal sensing and stimulation functionalities of recent research are addressed. Next, issues that arise when combining functionalities of conventional metal-based, opaque electrode arrays together with optical modalities—(1) photoelectric artifacts, (2) optical image blocking, and (3) light transmission efficiency—are introduced. Then, an introduction of advancing material candidates for transparent neural interfaces follows with the latest research.
GLUT1 production in cancer cells: a tragedy of the commons
Authors: Bukkuri Anuraag , Gatenby Robert A. , Brown Joel S.
Published: June 2022

The tragedy of the commons occurs when competition among individual members of a group leads to overexploitation of a shared resource to the detriment of the overall population. We hypothesize that cancer cells may engage in a tragedy of the commons when competing for a shared resource such as glucose. To formalize this notion, we create a game theoretic model of glucose uptake based on a cell’s investment in transporters relative to that of its neighboring cells. We show that production of transporters per cell increases as the number of competing cells in a microenvironment increases and nutrient uptake per cell decreases. Furthermore, the greater the resource availability, the more intense the tragedy of the commons at the ESS. Based on our simulations, cancer cells produce 2.2–2.7 times more glucose transporters than would produce optimal fitness for all group members. A tragedy of the commons affords novel therapeutic strategies. By simulating GLUT1 inhibitor and glucose deprivation treatments, we demonstrate a synergistic combination with standard-of-care therapies, while also displaying the existence of a trade-off between competition among cancer cells and depression of their gain function. Assuming cancer cell transporter production is heritable, we then show the potential for a sucker’s gambit therapy by exploiting this trade-off. By strategically changing environmental conditions, we can take advantage of cellular competition and gain function depression.
Grey wolf genomic history reveals a dual ancestry of dogs
Authors: Bergström Anders , Stanton David W. G. , Taron Ulrike H. , Frantz Laurent , Sinding Mikkel-Holger S. , Ersmark Erik , Pfrengle Saskia , Cassatt-Johnstone Molly , Lebrasseur Ophélie , Girdland-Flink Linus , Fernandes Daniel M. , Ollivier Morgane , Speidel Leo , Gopalakrishnan Shyam , Westbury Michael V. , Ramos-Madrigal Jazmin , Feuerborn Tatiana R. , Reiter Ella , Gretzinger Joscha , Münzel Susanne C. , Swali Pooja , Conard Nicholas J. , Carøe Christian , Haile James , Linderholm Anna , Androsov Semyon , Barnes Ian , Baumann Chris , Benecke Norbert , Bocherens Hervé , Brace Selina , Carden Ruth F. , Drucker Dorothée G. , Fedorov Sergey , Gasparik Mihály , Germonpré Mietje , Grigoriev Semyon , Groves Pam , Hertwig Stefan T. , Ivanova Varvara V. , Janssens Luc , Jennings Richard P. , Kasparov Aleksei K. , Kirillova Irina V. , Kurmaniyazov Islam , Kuzmin Yaroslav V. , Kosintsev Pavel A. , Lázničková-Galetová Martina , Leduc Charlotte , Nikolskiy Pavel , Nussbaumer Marc , O’Drisceoil Cóilín , Orlando Ludovic , Outram Alan , Pavlova Elena Y. , Perri Angela R. , Pilot Małgorzata , Pitulko Vladimir V. , Plotnikov Valerii V. , Protopopov Albert V. , Rehazek André , Sablin Mikhail , Seguin-Orlando Andaine , Storå Jan , Verjux Christian , Zaibert Victor F. , Zazula Grant , Crombé Philippe , Hansen Anders J. , Willerslev Eske , Leonard Jennifer A. , Götherström Anders , Pinhasi Ron , Schuenemann Verena J. , Hofreiter Michael , Gilbert M. Thomas P. , Shapiro Beth , Larson Greger , Krause Johannes , Dalén Love , Skoglund Pontus
Published: June 2022

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1–8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
Optimization of avian perching manoeuvres
Authors: KleinHeerenbrink Marco , France Lydia A. , Brighton Caroline H. , Taylor Graham K.
Published: June 2022

Perching at speed is among the most demanding flight behaviours that birds perform1,2 and is beyond the capability of most autonomous vehicles. Smaller birds may touch down by hovering3–8, but larger birds typically swoop up to perch1,2—presumably because the adverse scaling of their power margin prohibits hovering9 and because swooping upwards transfers kinetic to potential energy before collision1,2,10. Perching demands precise control of velocity and pose11–14, particularly in larger birds for which scale effects make collisions especially hazardous6,15. However, whereas cruising behaviours such as migration and commuting typically minimize the cost of transport or time of flight16, the optimization of such unsteady flight manoeuvres remains largely unexplored7,17. Here we show that the swooping trajectories of perching Harris’ hawks (Parabuteo unicinctus) minimize neither time nor energy alone, but rather minimize the distance flown after stalling. By combining motion capture data from 1,576 flights with flight dynamics modelling, we find that the birds’ choice of where to transition from powered dive to unpowered climb minimizes the distance over which high lift coefficients are required. Time and energy are therefore invested to provide the control authority needed to glide safely to the perch, rather than being minimized directly as in technical implementations of autonomous perching under nonlinear feedback control12 and deep reinforcement learning18,19. Naive birds learn this behaviour on the fly, so our findings suggest a heuristic principle that could guide reinforcement learning of autonomous perching.
Mitochondrial RNA modifications shape metabolic plasticity in metastasis
Authors: Delaunay Sylvain , Pascual Gloria , Feng Bohai , Klann Kevin , Behm Mikaela , Hotz-Wagenblatt Agnes , Richter Karsten , Zaoui Karim , Herpel Esther , Münch Christian , Dietmann Sabine , Hess Jochen , Benitah Salvador Aznar , Frye Michaela
Published: June 2022

Aggressive and metastatic cancers show enhanced metabolic plasticity1, but the precise underlying mechanisms of this remain unclear. Here we show how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent RNA modifications—5-methylcytosine (m5C) and its derivative 5-formylcytosine (f5C) (refs.2–4)—drive the translation of mitochondrial mRNA to power metastasis. Translation of mitochondrially encoded subunits of the oxidative phosphorylation complex depends on the formation of m5C at position 34 in mitochondrial tRNAMet. m5C-deficient human oral cancer cells exhibit increased levels of glycolysis and changes in their mitochondrial function that do not affect cell viability or primary tumour growth in vivo; however, metabolic plasticity is severely impaired as mitochondrial m5C-deficient tumours do not metastasize efficiently. We discovered that CD36-dependent non-dividing, metastasis-initiating tumour cells require mitochondrial m5C to activate invasion and dissemination. Moreover, a mitochondria-driven gene signature in patients with head and neck cancer is predictive for metastasis and disease progression. Finally, we confirm that this metabolic switch that allows the metastasis of tumour cells can be pharmacologically targeted through the inhibition of mitochondrial mRNA translation in vivo. Together, our results reveal that site-specific mitochondrial RNA modifications could be therapeutic targets to combat metastasis.
Increasing the resilience of plant immunity to a warming climate
Authors: Kim Jong Hum , Castroverde Christian Danve M. , Huang Shuai , Li Chao , Hilleary Richard , Seroka Adam , Sohrabi Reza , Medina-Yerena Diana , Huot Bethany , Wang Jie , Nomura Kinya , Marr Sharon K. , Wildermuth Mary C. , Chen Tao , MacMicking John D. , He Sheng Yang
Published: June 2022

Extreme weather conditions associated with climate change affect many aspects of plant and animal life, including the response to infectious diseases. Production of salicylic acid (SA), a central plant defence hormone1–3, is particularly vulnerable to suppression by short periods of hot weather above the normal plant growth temperature range via an unknown mechanism4–7. Here we show that suppression of SA production in Arabidopsis thaliana at 28 °C is independent of PHYTOCHROME B8,9 (phyB) and EARLY FLOWERING 310 (ELF3), which regulate thermo-responsive plant growth and development. Instead, we found that formation of GUANYLATE BINDING PROTEIN-LIKE 3 (GBPL3) defence-activated biomolecular condensates11 (GDACs) was reduced at the higher growth temperature. The altered GDAC formation in vivo is linked to impaired recruitment of GBPL3 and SA-associated Mediator subunits to the promoters of CBP60g and SARD1, which encode master immune transcription factors. Unlike many other SA signalling components, including the SA receptor and biosynthetic genes, optimized CBP60g expression was sufficient to broadly restore SA production, basal immunity and effector-triggered immunity at the elevated growth temperature without significant growth trade-offs. CBP60g family transcription factors are widely conserved in plants12. These results have implications for safeguarding the plant immune system as well as understanding the concept of the plant–pathogen–environment disease triangle and the emergence of new disease epidemics in a warming climate.
A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel
Authors: Feng Peiqiang , Wu Xudong , Erramilli Satchal K. , Paulo Joao A. , Knejski Pawel , Gygi Steven P. , Kossiakoff Anthony A. , Rapoport Tom A.
Published: June 2022

Peroxisomes are ubiquitous organelles that house various metabolic reactions and are essential for human health1–4. Luminal peroxisomal proteins are imported from the cytosol by mobile receptors, which then recycle back to the cytosol by a poorly understood process1–4. Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprising three RING finger domain-containing proteins (Pex2, Pex10 and Pex12)5,6. Here we report a cryo-electron microscopy structure of the ligase complex, which together with biochemical and in vivo experiments reveals its function as a retrotranslocation channel for peroxisomal import receptors. Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel. The three ring finger domains form a cytosolic tower, with ring finger 2 (RF2) positioned above the channel pore. We propose that the N terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable extraction into the cytosol. If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded. This polyubiquitylation pathway also maintains the homeostasis of other peroxisomal import factors. Our results clarify a crucial step during peroxisomal protein import and reveal why mutations in the ligase complex cause human disease.
Increased acid sphingomyelinase levels in pediatric patients with obesity
Authors: Mameli Chiara , Carnovale Carla , Ambrogi Federico , Infante Gabriele , Biejat Paulina Roux , Napoli Alessandra , Coazzoli Marco , Calcaterra Valeria , Schneider Laura , Perazzi Chiara , Zuccotti Gianvincenzo , Clementi Emilio , Moscheni Claudia , Perrotta Cristiana
Published: June 2022

The level of secretory acid sphingomyelinase (S-ASM), a key enzyme in the sphingolipid metabolism, is elevated in a variety of human diseases, including in the serum of obese adults. Alterations in S-ASM were also found to induce morphological changes in erythrocytes. Consequently, the inhibition of S-ASM by functional Inhibitors of ASM (FIASMA) may have broad clinical implications. The purpose of this study was to assess S-ASM activity in pediatric patients with obesity and healthy matched controls, as well as to investigate the erythrocyte morphology using transmission electron microscopy. We recruited 46 obese patients (mean age 11 ± 2.9 years) and 44 controls (mean age 10.8 ± 2.9 years). S-ASM activity was significantly higher (Wilcoxon signed-rank test p-value: 0.004) in obese patients (mean 396.4 ± 49.7 pmol/ml/h) than in controls (mean 373.7 ± 23.1 pmol/ml/h). No evidence of morphological differences in erythrocytes was found between the two populations. We then carried out a case–control study based on the spontaneous reporting system database to compare FIASMAs with NON-FIASMAs in terms of weight gain risk. Children who received FIASMA had a significantly lower frequency of weight gain reports than patients who took NON-FIASMA agents (p < 0.001). Our findings suggest there is an intriguing possibility that S-ASM may play a role in pediatric obesity. This pilot study could serve as the basis for future studies in this interesting field of research.
Spatial solitons in an electrically driven graphene multilayer medium
Authors: Shaukat Muzzamal Iqbal , Qasymeh Montasir , Eleuch Hichem
Published: June 2022

We investigate the evolution of coupled optical solitons in a multilayer graphene medium. The considered graphene medium is subjected to microwave voltage biasing. The coupled two optical solitons emerge through the electrical (i.e., microwave voltage) perturbation of the effective permittivity of the graphene multilayer. We show that the coupled solitons are electrically adjustable by controlling the amplitude and frequency of the biasing microwave voltage. Importantly, this proposed regime of electrically controlled optical solitons offers a modality to generate entangled optical solitons and two-mode squeezed solitons. Furthermore, the hybrid interaction that includes both the driving microwave voltage and the optical solitons yields a platform to combine the two worlds of quantum photonics and quantum superconducting systems.
Intra- and inter-examination reproducibility of T2 mapping for temporomandibular joint assessment at 3.0 T
Authors: Wongratwanich Pongsapak , Nagasaki Toshikazu , Shimabukuro Kiichi , Konishi Masaru , Ohtsuka Masahiko , Suei Yoshikazu , Nakamoto Takashi , Akiyama Yuji , Awai Kazuo , Kakimoto Naoya
Published: June 2022

T2 mapping allows quantification of the temporomandibular joint (TMJ) ultrastructural degeneration. The study aimed to assess intra- and inter-examination reproducibility of T2 mapping for TMJ evaluation at 3.0 Tesla (T). Seventeen volunteers, regardless of temporomandibular disorder (TMD) diagnosis, received magnetic resonance (MR) examination at 3.0 T. T2 mapping was performed twice (> 5 min between sessions without repositioning) on 12 volunteers to ensure intra-examination reproducibility. Nine volunteers underwent two examinations (> 6 months) to ensure inter-examination reproducibility. The regions of interest (ROIs) of the articular disc and retrodiscal tissue were manually selected and calculated. The mean T2 values of the articular disc and retrodiscal tissue were 25.3 ± 3.0 and 30.0 ± 4.1 ms, respectively. T2 mapping showed excellent intra-examination intraclass correlation coefficients (ICCs) for both articular disc (0.923) and retrodiscal tissue (0.951). Very strong correlations (r) were observed in both articular disc (0.928) and retrodiscal tissue (0.953) (P < .001). Inter-examination reproducibility also demonstrated that the ICCs were excellent (0.918, 0.935) on both ROIs. T2 values between first and second examinations were strongly correlated (r = 0.921, 0.939) (P < .001). In conclusion, T2 mapping seems to be a promising tool for TMJ assessment, regardless of the TMJ condition.
Unifying turbulent dynamics framework distinguishes different brain states
Authors: Escrichs Anira , Perl Yonatan Sanz , Uribe Carme , Camara Estela , Türker Basak , Pyatigorskaya Nadya , López-González Ane , Pallavicini Carla , Panda Rajanikant , Annen Jitka , Gosseries Olivia , Laureys Steven , Naccache Lionel , Sitt Jacobo D. , Laufs Helmut , Tagliazucchi Enzo , Kringelbach Morten L. , Deco Gustavo
Published: June 2022

Significant advances have been made by identifying the levels of synchrony of the underlying dynamics of a given brain state. This research has demonstrated that non-conscious dynamics tend to be more synchronous than in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that different brain states are underpinned by dissociable spatiotemporal dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep and disorders of consciousness after coma). The model-free approach was based on Kuramoto’s turbulence framework using coupled oscillators. This was extended by a measure of the information cascade across spatial scales. Complementarily, the model-based approach used exhaustive in silico perturbations of whole-brain models fitted to these measures. This allowed studying of the information encoding capabilities in given brain states. Overall, this framework demonstrates that elements from turbulence theory provide excellent tools for describing and differentiating between brain states.